Chapter 47. Chronic Pain Management

• Pain may be classified according to pathophysiology (eg, nociceptive or neuropathic pain), etiology (eg, postoperative or cancer pain), or the affected area (eg, headache or low back pain).
• Nociceptive pain is caused by activation or sensitization of peripheral nociceptors, specialized receptors that transduce noxious stimuli. Neuropathic pain is the result of injury or acquired abnormalities of peripheral or central neural structures.
• Acute pain is caused by noxious stimulation due to injury, a disease process, or the abnormal function of muscle or viscera. It is nearly always nociceptive.
• Chronic pain is pain that persists beyond the usual course of an acute disease or after a reasonable time for healing to occur; this healing period can vary from 1 to 6 months. Chronic pain may be nociceptive, neuropathic, or mixed.
• Modulation of pain occurs peripherally at the nociceptor, in the spinal cord, or in supraspinal structures. This modulation can either inhibit (suppress) or facilitate (intensify) pain.
• At least three mechanisms are responsible for central sensitization in the spinal cord: (1) wind-up and sensitization of second-order wide dynamic range neurons; (2) dorsal horn neuron receptor field expansion; and (3) hyperexitability of flexion reflexes.
• Chronic pain may be caused by a combination of peripheral, central, and psychological mechanisms.
• Moderate to severe acute pain, regardless of site, can affect the function of nearly every organ and may adversely influence perioperative morbidity and mortality.
• The evaluation of any patient with pain should include several key components. Information about location, onset, and quality of pain, as well as alleviating and exacerbating factors, should be obtained along with a pain history that includes previous therapies and changes in symptoms over time.
• Psychological evaluation is useful whenever medical evaluation fails to reveal an apparent cause for pain, pain intensity is disproportionate to disease or injury, or when depression or other psychological issues are apparent.
• Myofascial pain syndromes are common disorders characterized by aching muscle pain, muscle spasm, stiffness, weakness, and, occasionally, autonomic dysfunction.
• Ninety percent of disc herniations occur at L5-S1 or L4-L5. Symptoms usually develop following flexion injuries or heavy lifting and may be associated with bulging, protrusion, or extrusion of the disc.
• Back pain caused by spinal stenosis usually radiates into the buttocks, thighs, and legs. Termed pseudoclaudication or neurogenic claudication, the pain is characteristically worse with exercise and relieved by rest, particularly sitting with the spine flexed.
• Diabetic neuropathy is the most common type of neuropathic pain.
• Complex regional pain syndrome (CRPS) is a neuropathic pain disorder with significant autonomic features that is usually subdivided into two variants: CRPS 1, formerly known as reflex sympathetic dystrophy (RSD), and CRPS 2, formerly known as causalgia. The major difference between the two is the absence or presence, respectively, of documented nerve injury.
• Trigeminal neuralgia (tic douloureux) is classically unilateral and usually located in the V2 or V3 distribution of the trigeminal nerve. It has an electric shock quality lasting from seconds to minutes at a time and is often provoked by contact with a discrete trigger.
• Antidepressants are most useful for patients with neuropathic pain. These medications demonstrate an analgesic effect that occurs at a dose lower than needed for antidepressant activity.
• Anticonvulsant medications are useful for patients with neuropathic pain, especially trigeminal neuralgia and diabetic neuropathy.
• Patients who experience opioid tolerance require escalating doses of opioid to maintain the same analgesic effect. Physical dependence manifests in opioid withdrawal when the opioid medication is either abruptly discontinued or the dose is abruptly and significantly decreased. Psychological dependence, characterized by behavioral changes focusing on drug craving, is rare in cancer patients.
• Complications of stellate block include intravascular and subarachnoid injection, hematoma, pneumothorax, epidural anesthesia, brachial plexus block, hoarseness due to blockade of the recurrent laryngeal nerve, and, rarely, osteomyelitis or mediastinitis.
• Ganglion impar block is effective for patients with visceral or sympathetically maintained pain in the perineal area.
• Neurolytic blocks are indicated for patients with severe, intractable cancer pain in whom more conventional therapy proves inadequate or conventional analgesic modalities are accompanied by unacceptable side effects.
• Spinal cord stimulation may be most effective for neuropathic pain; accepted indications include sympathetically mediated pain, spinal cord lesions with localized segmental pain, phantom limb pain, ischemic lower extremity pain due to peripheral vascular disease, adhesive arachnoiditis, peripheral neuropathies, post-thoracotomy pain, intercostal neuralgia, postherpetic neuralgia, angina, visceral abdominal pain, and visceral pelvic pain.
• Patients with pathological or osteoporotic vertebral compression fracture may benefit from vertebral augmentation with polymethylmethacrylate cement. Vertebroplasty involves injection of the cement through the trocar needle. Kyphoplasty involves inflation of a balloon inserted through a percutaneously placed trocar needle, with subsequent injection of cement.
• Acupuncture can be a useful adjunct for patients with chronic pain, particularly that associated with chronic musculoskeletal disorders and headaches.

Pain—the most common symptom that brings patients to see a physician—is nearly always a manifestation of a pathological process. This symptom may have a wide variety of causes ranging from relatively benign conditions to acute injury, myocardial ischemia, degenerative changes, or malignancy. In most cases, after a diagnosis is made, conservative measures are prescribed and the patient responds successfully. In others, referral to a pain medicine specialist for evaluation and treatment improves outcomes and conserves health care resources. In still other situations, pain persists and patients develop chronic pain, the cause of which remains obscure after preliminary investigations have excluded serious and life-threatening illnesses and, if warranted, surgical intervention has either failed to relieve pain or has produced a new pain syndrome.

The term pain management in a general sense applies to the entire discipline of anesthesiology, but its modern usage more specifically involves management of pain throughout the perioperative period as well as nonsurgical pain in both inpatient and outpatient settings. Pain medicine practice may be broadly divided into acute and chronic pain management. The former primarily deals with patients recovering from surgery or with acute medical conditions in a hospital setting (see Chapter 48), whereas the latter includes diverse groups of patients almost always seen in the outpatient setting. Unfortunately, this distinction is artificial and considerable overlap exists; a good example is the patient with cancer who frequently requires short- and long-term pain management in both inpatient and outpatient settings.

The contemporary practice of pain management is not limited to anesthesiologists but often includes other physicians (physiatrists, surgeons, internists, oncologists, psychiatrists, and neurologists) and nonphysicians (psychologists, physical therapists, acupuncturists, and hypnotists). The most effective approaches are multidisciplinary, in which the patient is evaluated by one or more physicians who conduct an initial examination, make a diagnosis, and formulate a treatment plan, and where subsequent evaluation and use of the services and resources of other health care providers are readily available.

Anesthesiologists trained in pain management are in a unique position to coordinate multidisciplinary pain management centers because of their broad training in dealing with a wide variety of patients from surgical, obstetric, pediatric, and medical subspecialties and their expertise in clinical pharmacology and applied neuroanatomy, including the use of peripheral and central nerve blocks.

Definitions & Classification of Pain

Like other conscious sensations, normal pain perception depends on specialized neurons that function as receptors, detecting the stimulus, and then transducing and conducting it to the central nervous system. Sensation is often described as either protopathic (noxious) or epicritic (nonnoxious). Epicritic sensations (light touch, pressure, proprioception, and temperature discrimination) are characterized by low-threshold receptors and are generally conducted by large myelinated nerve fibers. In contrast, protopathic sensations (pain) are detected by high-threshold receptors and conducted by smaller, lightly myelinated (Aδ) and unmyelinated (C) nerve fibers.

What Is Pain?

Pain is not just a sensory modality but an experience. The International Association for the Study of Pain defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” This definition recognizes the interplay between the objective, physiological sensory aspects of pain and its subjective, emotional, and psychological components. The response to pain can be highly variable among different individuals as well as in the same person at different times.

The term nociception is derived from noci (Latin for harm or injury) and is used to describe neural responses to traumatic or noxious stimuli. All nociception produces pain, but not all pain results from nociception. Many patients experience pain in the absence of noxious stimuli. It is therefore clinically useful to divide pain into one of two categories: (1) acute pain, which is primarily due to nociception, and (2) chronic pain, which may be due to nociception, but in which psychological and behavioral factors often play a major role. Table 47-1 lists terms frequently used in describing pain.

There are differences in pain perception related to gender and age. Research has confirmed differences in pain experiences and coping strategies between genders, and there is ongoing investigation into exactly how this processing differs. Brain activation differs between genders, with men particularly influenced by the type and intensity of a noxious stimulus. Brain imaging patterns differ as well. Some of these differences decrease with age and may disappear after age 40.

Acute Pain

Somatic Pain

Somatic pain can be further classified as superficial or deep. Superficial somatic pain is due to nociceptive input arising from skin, subcutaneous tissues, and mucous membranes. It is characteristically well localized and described as a sharp, pricking, throbbing, or burning sensation.

Deep somatic pain arises from muscles, tendons, joints, or bones. In contrast to superficial somatic pain, it usually has a dull, aching quality and is less well localized. An additional feature is that both the intensity and duration of the stimulus affect the degree of localization. For example, pain following brief minor trauma to the elbow joint is localized to the elbow, but severe or sustained trauma often causes pain in the whole arm.

Visceral Pain

Visceral acute pain is due to a disease process or abnormal function involving an internal organ or its covering (eg, parietal pleura, pericardium, or peritoneum). Four subtypes are described: (1) true localized visceral pain, (2) localized parietal pain, (3) referred visceral pain, and (4) referred parietal pain. True visceral pain is dull, diffuse, and usually midline. It is frequently associated with abnormal sympathetic or parasympathetic activity causing nausea, vomiting, sweating, and changes in blood pressure and heart rate. Parietal pain is typically sharp and often described as a stabbing sensation that is either localized to the area around the organ or referred to a distant site (Table 47-2). The phenomenon of visceral or parietal pain referred to cutaneous areas results from patterns of embryological development and migration of tissues, and the convergence of visceral and somatic afferent input into the central nervous system. Thus, pain associated with disease processes involving the peritoneum or pleura over the central diaphragm is frequently referred to the neck and shoulder, whereas pain from disease processes affecting the parietal surfaces of the peripheral diaphragm is referred to the chest or upper abdominal wall.

Chronic Pain

The most common forms of chronic pain include those associated with musculoskeletal disorders, chronic visceral disorders, lesions of peripheral nerves, nerve roots, or dorsal root ganglia (including diabetic neuropathy, causalgia, phantom limb pain, and postherpetic neuralgia), lesions of the central nervous system (stroke, spinal cord injury, and multiple sclerosis), and cancer pain. The pain of most musculoskeletal disorders (eg, rheumatoid arthritis and osteoarthritis) is primarily nociceptive, whereas pain associated with peripheral or central neural disorders is primarily neuropathic. The pain associated with some disorders, eg, cancer and chronic back pain (particularly after surgery), is often mixed. Some clinicians use the term chronic benign pain when pain does not result from cancer. This terminology should be discouraged, however, because pain is never benign from the patient’s point of view, regardless of its cause.

Pain Pathways

Pain is conducted along three neuronal pathways that transmit noxious stimuli from the periphery to the cerebral cortex (Figure 47-1). The cell bodies of primary afferent neurons are located in the dorsal root ganglia, which lie in the vertebral foramina at each spinal cord level. Each neuron has a single axon that bifurcates, sending one end to the peripheral tissues it innervates and the other into the dorsal horn of the spinal cord. In the dorsal horn, the primary afferent neuron synapses with a second-order neuron whose axon crosses the midline and ascends in the contralateral spinothalamic tract to reach the thalamus. Second-order neurons synapse in thalamic nuclei with third-order neurons, which in turn send projections through the internal capsule and corona radiata to the postcentral gyrus of the cerebral cortex (Figure 47-2).

First-Order Neurons

The majority of first-order neurons send the proximal end of their axons into the spinal cord via the dorsal (sensory) spinal root at each cervical, thoracic, lumbar, and sacral level. Some unmyelinated afferent (C) fibers have been shown to enter the spinal cord via the ventral nerve (motor) root, accounting for observations that some patients continue to feel pain even after transection of the dorsal nerve root (rhizotomy) and report pain following ventral root stimulation. Once in the dorsal horn, in addition to synapsing with second-order neurons, the axons of first-order neurons may synapse with interneurons, sympathetic neurons, and ventral horn motor neurons.

Pain fibers originating from the head are carried by the trigeminal (V), facial (VII), glossopharyngeal (IX), and vagal (X) nerves. The gasserian ganglion contains the cell bodies of sensory fibers in the ophthalmic, maxillary, and mandibular divisions of the trigeminal nerve. Cell bodies of first-order afferent neurons of the facial nerve are located in the geniculate ganglion; those of the glossopharyngeal nerve lie in its superior and petrosal ganglia; and those of the vagal nerve are located in the jugular ganglion (somatic) and the ganglion nodosum (visceral). The proximal axonal processes of the first-order neurons in these ganglia reach the brainstem nuclei via their respective cranial nerves, where they synapse with second-order neurons in brainstem nuclei.

Second-Order Neurons

As afferent fibers enter the spinal cord, they segregate according to size, with large, myelinated fibers becoming medial, and small, unmyelinated fibers becoming lateral. Pain fibers may ascend or descend one to three spinal cord segments in Lissauer’s tract before synapsing with second-order neurons in the gray matter of the ipsilateral dorsal horn. In many instances they communicate with second-order neurons through interneurons.

Spinal cord gray matter was divided by Rexed into 10 laminae (Figure 47-3 and Table 47-3). The first six laminae, which make up the dorsal horn, receive all afferent neural activity and represent the principal site of modulation of pain by ascending and descending neural pathways. Second-order neurons are either nociceptive-specific or wide dynamic range (WDR) neurons. Nociceptive-specific neurons serve only noxious stimuli, but WDR neurons also receive nonnoxious afferent input from Aβ, Aδ, and C fibers. Nociceptive-specific neurons are arranged somatotopically in lamina I and have discrete, somatic receptive fields; they are normally silent and respond only to high-threshold noxious stimulation, poorly encoding stimulus intensity. WDR neurons are the most prevalent cell type in the dorsal horn. Although they are found throughout the dorsal horn, WDR neurons are most abundant in lamina V. During repeated stimulation, WDR neurons characteristically increase their firing rate exponentially in a graded fashion (“wind-up”), even with the same stimulus intensity. They also have large receptive fields compared with nociceptive-specific neurons.

Most nociceptive C fibers send collaterals to, or terminate on, second-order neurons in laminae I and II, and, to a lesser extent, in lamina V. In contrast, nociceptive Aδ fibers synapse mainly in laminae I and V, and, to a lesser degree, in lamina X. Lamina I responds primarily to noxious (nociceptive) stimuli from cutaneous and deep somatic tissues. Lamina II, also called the substantia gelatinosa, contains many interneurons and is believed to play a major role in processing and modulating nociceptive input from cutaneous nociceptors. It is also of special interest because it is believed to be a major site of action for opioids. Laminae III and IV primarily receive nonnociceptive sensory input. Laminae VIII and IX make up the anterior (motor) horn. Lamina VII is the intermediolateral column and contains the cell bodies of preganglionic sympathetic neurons.

Visceral afferents terminate primarily in lamina V, and, to a lesser extent, in lamina I. These two laminae represent points of central convergence between somatic and visceral inputs. Lamina V responds to both noxious and nonnoxious sensory input and receives both visceral and somatic pain afferents. The phenomenon of convergence between visceral and somatic sensory input is manifested clinically as referred pain (see Table 47-2). Compared with somatic fibers, visceral nociceptive fibers are fewer in number, more widely distributed, proportionately activate a larger number of spinal neurons, and are not organized somatotopically.

The Spinothalamic Tract

The axons of most second-order neurons cross the midline close to their dermatomal level of origin (at the anterior commissure) to the contralateral side of the spinal cord before they form the spinothalamic tract and send their fibers to the thalamus, the reticular formation, the nucleus raphe magnus, and the periaqueductal gray. The spinothalamic tract, which is classically considered the major pain pathway, lies anterolaterally in the white matter of the spinal cord (Figure 47-4). This ascending tract can be divided into a lateral and a medial tract. The lateral spinothalamic (neospinothalamic) tract projects mainly to the ventral posterolateral nucleus of the thalamus and carries discriminative aspects of pain, such as location, intensity, and duration. The medial spinothalamic (paleospinothalamic) tract projects to the medial thalamus and is responsible for mediating the autonomic and unpleasant emotional perceptions of pain. Some spinothalamic fibers also project to the periaqueductal gray and thus may be an important link between the ascending and descending pathways. Collateral fibers also project to the reticular activating system and the hypothalamus; these are likely responsible for the arousal response to pain.

Alternate Pain Pathways

As with epicritic sensation, pain fibers ascend diffusely, ipsilaterally, and contralaterally; some patients continue to perceive pain following ablation of the contralateral spinothalamic tract, and therefore other ascending pain pathways are also important. The spinoreticular tract is thought to mediate arousal and autonomic responses to pain. The spinomesencephalic tract may be important in activating antinociceptive, descending pathways, because it has some projections to the periaqueductal gray. The spinohypothalamic and spinotelencephalic tracts activate the hypothalamus and evoke emotional behavior. The spinocervical tract ascends uncrossed to the lateral cervical nucleus, which relays the fibers to the contralateral thalamus; this tract is likely a major alternative pathway for pain. Lastly, some fibers in the dorsal columns (which mainly carry light touch and proprioception) are responsive to pain; they ascend medially and ipsilaterally.

Integration with the Sympathetic and Motor Systems

Somatic and visceral afferents are fully integrated with the skeletal motor and sympathetic systems in the spinal cord, brainstem, and higher centers. Afferent dorsal horn neurons synapse both directly and indirectly with anterior horn motor neurons. These synapses are responsible for the reflex muscle activity—whether normal or abnormal—that is associated with pain. In a similar fashion, synapses between afferent nociceptive neurons and sympathetic neurons in the intermediolateral column result in reflex sympathetically mediated vasoconstriction, smooth muscle spasm, and the release of catecholamines, both locally and from the adrenal medulla.

Third-Order Neurons

Third-order neurons are located in the thalamus and send fibers to somatosensory areas I and II in the postcentral gyrus of the parietal cortex and the superior wall of the sylvian fissure, respectively. Perception and discrete localization of pain take place in these cortical areas. Although most neurons from the lateral thalamic nuclei project to the primary somatosensory cortex, neurons from the intralaminar and medial nuclei project to the anterior cingulate gyrus and are likely involved in mediating the suffering and emotional components of pain.

Physiology of Nociception

Nociceptors

Nociceptors are characterized by a high threshold for activation and encode the intensity of stimulation by increasing their discharge rates in a graded fashion. Following repeated stimulation, they characteristically display delayed adaptation, sensitization, and afterdischarges.

Noxious sensations can often be broken down into two components: a fast, sharp, and well-localized sensation (“first pain”), which is conducted with a short latency (0.1 s) by Aδ fibers (tested by pinprick); and a slower onset, duller, and often poorly localized sensation (“second pain”), which is conducted by C fibers. In contrast to epicritic sensation, which may be transduced by specialized end organs on the afferent neuron (eg, pacinian corpuscle for touch), protopathic sensation is transduced mainly by free nerve endings.

Most nociceptors are free nerve endings that sense heat and mechanical and chemical tissue damage. Types include (1) mechanonociceptors, which respond to pinch and pinprick, (2) silent nociceptors, which respond only in the presence of inflammation, and (3) polymodal mechanoheat nociceptors. The last are most prevalent and respond to excessive pressure, extremes of temperature (>42°C and <40°C), and noxious substances such as bradykinin, histamine, serotonin (5-hydroxytryptamine or 5-HT), H+, K+, some prostaglandins, capsaicin, and possibly adenosine triphosphate. At least two nociceptor receptors (containing ion channels in nerve endings) have been identified, TRPV1 and TRPV2. Both respond to high temperatures. Capsaicin stimulates the TRPV1 receptor. Polymodal nociceptors are slow to adapt to strong pressure and display heat sensitization.

Cutaneous Nociceptors

Nociceptors are present in both somatic and visceral tissues. Primary afferent neurons reach tissues by traveling along spinal somatic, sympathetic, or parasympathetic nerves. Somatic nociceptors include those in skin (cutaneous) and deep tissues (muscle, tendons, fascia, and bone), whereas visceral nociceptors include those in internal organs. The cornea and tooth pulp are unique in that they are almost exclusively innervated by nociceptive Aδ and C fibers.

Deep Somatic Nociceptors

Deep somatic nociceptors are less sensitive to noxious stimuli than cutaneous nociceptors but are easily sensitized by inflammation. The pain arising from them is characteristically dull and poorly localized. Specific nociceptors exist in muscles and joint capsules, and they respond to mechanical, thermal, and chemical stimuli.

Visceral Nociceptors

Visceral organs are generally insensitive tissues that mostly contain silent nociceptors. Some organs appear to have specific nociceptors, such as the heart, lung, testis, and bile ducts. Most other organs, such as the intestines, are innervated by polymodal nociceptors that respond to smooth muscle spasm, ischemia, and inflammation. These receptors generally do not respond to the cutting, burning, or crushing that occurs during surgery. A few organs, such as the brain, lack nociceptors altogether; however, the brain’s meningeal coverings do contain nociceptors.

Like somatic nociceptors, those in the viscera are the free nerve endings of primary afferent neurons whose cell bodies lie in the dorsal horn. These afferent nerve fibers, however, frequently travel with efferent sympathetic nerve fibers to reach the viscera. Afferent activity from these neurons enters the spinal cord between T1 and L2. Nociceptive C fibers from the esophagus, larynx, and trachea travel with the vagus nerve to enter the nucleus solitarius in the brainstem. Afferent pain fibers from the bladder, prostate, rectum, cervix and urethra, and genitalia are transmitted into the spinal cord via parasympathetic nerves at the level of the S2-S4 nerve roots. Though relatively few compared with somatic pain fibers, fibers from primary visceral afferent neurons enter the cord and synapse more diffusely with single fibers, often synapsing with multiple dermatomal levels and often crossing to the contralateral dorsal horn.

Chemical Mediators of Pain

Several neuropeptides and excitatory amino acids function as neurotransmitters for afferent neurons subserving pain (Table 47-4). Many, if not most, of these neurons contain more than one neurotransmitter, which are simultaneously released. The most important of these peptides are substance P and calcitonin gene-related peptide (CGRP). Glutamate is the most important excitatory amino acid.

Substance P is an 11 amino acid peptide that is synthesized and released by first-order neurons both peripherally and in the dorsal horn. Also found in other parts of the nervous system and the intestines, it facilitates transmission in pain pathways via neurokinin-1 receptor activation. In the periphery, substance P neurons send collaterals that are closely associated with blood vessels, sweat glands, hair follicles, and mast cells in the dermis. Substance P sensitizes nociceptors, degranulates histamine from mast cells and 5-HT from platelets, and is a potent vasodilator and chemoattractant for leukocytes. Substance P-releasing neurons also innervate the viscera and send collateral fibers to paravertebral sympathetic ganglia; intense stimulation of viscera, therefore, can cause direct postganglionic sympathetic discharge.

Both opioid and α2-adrenergic receptors have been described on or near the terminals of unmyelinated peripheral nerves. Although their physiological role is not clear, the latter may explain the observed analgesia of peripherally applied opioids, particularly in the presence of inflammation.

Modulation of Pain

Peripheral Modulation of Pain

Nociceptors and their neurons display sensitization following repeated stimulation. Sensitization may be manifested as an enhanced response to noxious stimulation or a newly acquired responsiveness to a wider range of stimuli, including nonnoxious stimuli.

Primary Hyperalgesia

Sensitization of nociceptors results in a decrease in threshold, an increase in the frequency response to the same stimulus intensity, a decrease in response latency, and spontaneous firing even after cessation of the stimulus (afterdischarges). Such sensitization commonly occurs with injury and following application of heat. Primary hyperalgesia is mediated by the release of noxious substances from damaged tissues. Histamine is released from mast cells, basophils, and platelets, whereas serotonin is released from mast cells and platelets. Bradykinin is released from tissues following activation of factor XII. Bradykinin activates free nerve endings via specific B1 and B2 receptors.

Prostaglandins are produced following tissue damage by the action of phospholipase A2 on phospholipids released from cell membranes to form arachidonic acid (Figure 47-5). The cyclooxygenase (COX) pathway then converts the latter into endoperoxides, which in turn are transformed into prostacyclin and prostaglandin E2 (PGE2). PGE2 directly activates free nerve endings, whereas prostacyclin potentiates the edema from bradykinin. The lipoxygenase pathway converts arachidonic acid into hydroperoxy compounds, which are subsequently converted into leukotrienes. The role of the latter is not well defined, but they appear to potentiate certain types of pain. Pharmacological agents such as acetylsalicylic acid (ASA, or aspirin), acetaminophen, and nonsteroidal antiinflammatory drugs (NSAIDs) produce analgesia by inhibition of COX. The analgesic effect of corticosteroids is likely the result of inhibition of prostaglandin production through blockade of phospholipase A2 activation.

Secondary Hyperalgesia

Neurogenic inflammation, also called secondary hyperalgesia, plays an important role in peripheral sensitization following injury. It is manifested by the “triple response (of Lewis)” of a red flush around the site of injury (flare), local tissue edema, and sensitization to noxious stimuli. Secondary hyperalgesia is primarily due to antidromic release of substance P (and probably CGRP). Substance P degranulates histamine and 5-HT, vasodilates blood vessels, causes tissue edema, and induces the formation of leukotrienes. The neural origin of this response is supported by the following findings: (1) it can be produced by electrical stimulation of a sensory nerve, (2) it is not observed in denervated skin, and (3) it is diminished by injection of a local anesthetic. Capsaicin applied topically in a gel, cream, or patch depletes substance P and diminishes neurogenic inflammation, and is useful for some patients with postherpetic neuralgia.

Central Modulation of Pain

Facilitation

1. Wind-up and sensitization of second-order neurons. WDR neurons increase their frequency of discharge with the same repetitive stimuli and exhibit prolonged discharge, even after afferent C fiber input has stopped.

2. Receptor field expansion. Dorsal horn neurons increase their receptive fields such that adjacent neurons become responsive to stimuli (whether noxious or not) to which they were previously unresponsive.

3. Hyperexcitability of flexion reflexes. Enhancement of flexion reflexes is observed both ipsilaterally and contralaterally.

Neurochemical mediators of central sensitization include substance P, CGRP, vasoactive intestinal peptide (VIP), cholecystokinin (CCK), angiotensin, and galanin, as well as the excitatory amino acids L-glutamate and L-aspartate. These substances trigger changes in membrane excitability by interacting with G protein-coupled membrane receptors on neurons (Figure 47-5).

Glutamate and aspartate play important roles in wind-up, via activation of N-methyl-D-aspartate (NMDA) and other receptor mechanisms, and in the induction and maintenance of central sensitization. Activation of NMDA receptors also induces nitric oxide synthetase, increasing formation of nitric oxide. Both prostaglandins and nitric oxide facilitate the release of excitatory amino acids in the spinal cord. Thus, COX inhibitors such as ASA and NSAIDs have important analgesic actions in the spinal cord.

Inhibition

Transmission of nociceptive input in the spinal cord can be inhibited by segmental activity in the cord itself, as well as by descending neural activity from supraspinal centers.

Segmental Inhibition

Activation of large afferent fibers subserving sensation inhibits WDR neuron and spinothalamic tract activity. Moreover, activation of noxious stimuli in noncontiguous parts of the body inhibits WDR neurons at other levels, which may explain why pain in one part of the body inhibits pain in other parts. These two phenomena support a “gate” theory for pain processing in the spinal cord.

Glycine and γ-aminobutyric acid (GABA) are amino acids that function as inhibitory neurotransmitters and likely play an important role in segmental inhibition of pain in the spinal cord. Antagonism of glycine and GABA results in powerful facilitation of WDR neurons and produces allodynia and hyperesthesia. There are two subtypes of GABA receptors: GABAA, of which muscimol is an agonist, and GABAB, of which baclofen is an agonist. Segmental inhibition appears to be mediated by GABAB receptor activity. The GABAA receptor functions as a Cl− channel, and benzodiazepines activate this channel. Activation of glycine receptors also increases Cl− conductance across neuronal cell membranes. The action of glycine is more complex than that of GABA, because the former also has a facilitatory (excitatory) effect on the NMDA receptor.

Adenosine also modulates nociceptive activity in the dorsal horn. At least two receptors are known: A1, which inhibits adenyl cyclase, and A2, which stimulates adenyl cyclase. The A1 receptor mediates adenosine’s antinociceptive action. Methylxanthines can reverse this effect through phosphodiesterase inhibition.

Supraspinal Inhibition

Several supraspinal structures send fibers down the spinal cord to inhibit pain in the dorsal horn. Important sites of origin for these descending pathways include the periaqueductal gray, reticular formation, and nucleus raphe magnus (NRM). Stimulation of the periaqueductal gray area in the midbrain produces widespread analgesia in humans. Axons from these tracts act presynaptically on primary afferent neurons and postsynaptically on second-order neurons (or interneurons). These pathways mediate their antinociceptive action via α2-adrenergic, serotonergic, and opiate (μ, δ, and κ) receptor mechanisms. The role of monoamines in pain inhibition explains the analgesic efficacy of antidepressants that block reuptake of catecholamines and serotonin.

Inhibitory adrenergic pathways originate primarily from the periaqueductal gray area and the reticular formation. Norepinephrine mediates this action via activation of presynaptic or postsynaptic α2 receptors. At least part of the descending inhibition from the periaqueductal gray is relayed first to the NRM and medullary reticular formation; serotonergic fibers from the NRM then relay the inhibition to dorsal horn neurons via the dorsolateral funiculus.

The endogenous opiate system (primarily the NRM and reticular formation) acts via methionine enkephalin, leucine enkephalin, and β-endorphin, all of which are antagonized by naloxone. These opioids act presynaptically to hyperpolarize primary afferent neurons and inhibit the release of substance P; they also appear to cause some postsynaptic inhibition. Exogenous opioids preferentially act postsynaptically on the second-order neurons or interneurons in the substantia gelatinosa.

Pathophysiology of Chronic Pain

Neuropathic pain involves peripheral-central and central neural mechanisms that are complex and generally associated with partial or complete lesions of peripheral nerves, dorsal root ganglia, nerve roots, or more central structures (Table 47-5). Peripheral mechanisms include spontaneous discharges; sensitization of receptors to mechanical, thermal, and chemical stimuli; and up-regulation of adrenergic receptors. Neural inflammation may also be present. Systemic administration of local anesthetics and anticonvulsants has been shown to suppress the spontaneous firing of sensitized or traumatized neurons. This observation is supported by the efficacy of agents such as lidocaine, mexiletine, and carbamazepine in many patients with neuropathic pain. Central mechanisms include loss of segmental inhibition, wind-up of WDR neurons, spontaneous discharges in deafferentated neurons, and reorganization of neural connections.

The sympathetic nervous system appears to play a major role in some patients with chronic pain. The efficacy of sympathetic nerve blocks in some of these patients supports the concept of sympathetically maintained pain. Painful disorders that often respond to sympathetic blocks include complex regional pain syndrome, deafferentation syndromes due to nerve avulsion or amputations, and postherpetic neuralgia. However, the simplistic theory of heightened sympathetic activity resulting in vasoconstriction, edema, and hyperalgesia fails to account for the warm and erythematous phase observed in some patients. Similarly, clinical and experimental observations do not satisfactorily support the theory of ephaptic transmission between pain fibers and demyelinated sympathetic fibers.

Psychological mechanisms or environmental factors are rarely the sole mechanisms for chronic pain but are commonly seen in combination with other mechanisms (Table 47-6).

Systemic Responses to Pain

Systemic Responses to Acute Pain

Acute pain is typically associated with a neuroendocrine stress response that is proportional to pain intensity. The pain pathways mediating the afferent limb of this response are discussed above. The efferent limb is mediated by the sympathetic nervous and endocrine systems. Sympathetic activation increases efferent sympathetic tone to all viscera and releases catecholamines from the adrenal medulla. The hormonal response results from increased sympathetic tone and from hypothalamically mediated reflexes.

Cardiovascular Effects

Cardiovascular effects are often prominent and include hypertension, tachycardia, enhanced myocardial irritability, and increased systemic vascular resistance. Cardiac output increases in most normal patients but may decrease in patients with compromised ventricular function. Because of the increase in myocardial oxygen demand, pain can worsen or precipitate myocardial ischemia.

Respiratory Effects

An increase in total body oxygen consumption and carbon dioxide production necessitates a concomitant increase in minute ventilation. The latter increases the work of breathing, particularly in patients with underlying lung disease. Pain due to abdominal or thoracic incisions further compromises pulmonary function because of guarding (splinting). Decreased movement of the chest wall reduces tidal volume and functional residual capacity; this promotes atelectasis, intrapulmonary shunting, hypoxemia, and, less commonly, hypoventilation. Reductions in vital capacity impair coughing and clearing of secretions. Regardless of the pain’s location, prolonged bed rest or immobilization can produce similar changes in pulmonary function.

Gastrointestinal and Urinary Effects

Enhanced sympathetic tone increases sphincter tone and decreases intestinal and urinary motility, promoting ileus and urinary retention, respectively. Hypersecretion of gastric acid can promote stress ulceration and worsen the consequences of pulmonary aspiration. Nausea, vomiting, and constipation are common.

Endocrine Effects

Stress increases catabolic hormones (catecholamines, cortisol, and glucagon) and decreases anabolic hormones (insulin and testosterone). Patients develop a negative nitrogen balance, carbohydrate intolerance, and increased lipolysis. The increase in cortisol, renin, angiotensin, aldosterone, and antidiuretic hormone results in sodium retention, water retention, and secondary expansion of the extracellular space.

Hematological Effects

Stress-mediated increases in platelet adhesiveness, reduced fibrinolysis, and hypercoagulability have been reported.

Immune Effects

The neuroendocrine stress response produces leukocytosis and has been reported to depress the reticuloendothelial system. The latter predisposes patients to infection. Stress-related immunodepression may also enhance tumor growth and metastasis.

Psychological Effects

Anxiety and sleep disturbances are common reactions to acute pain. With prolonged duration of the pain, depression is not unusual. Some patients react with frustration and anger that may be directed at family, friends, or the medical staff.

Systemic Responses to Chronic Pain

The neuroendocrine stress response is generally observed only in patients with severe recurring pain due to peripheral (nociceptive) mechanisms and in patients with prominent central mechanisms such as pain associated with paraplegia. It is attenuated or absent in most patients with chronic pain. Sleep and affective disturbances, particularly depression, are often prominent. Many patients also experience significant changes in appetite (increase or decrease) and stresses on social relationships.

Pain Measurement

Reliable quantitation of pain severity helps determine therapeutic interventions and evaluate the efficacy of treatments. This is a challenge, however, because pain is a subjective experience that is influenced by psychological, cultural, and other variables. Clear definitions are necessary, because pain may be described in terms of tissue destruction or bodily or emotional reaction.

The numerical rating scale, Wong-Baker FACES rating scale, visual analog scale (VAS), and McGill Pain Questionnaire (MPQ) are most commonly used. In the numerical scale, 0 corresponds to no pain and 10 is intended to reflect the worst possible pain. The Wong-Baker FACES pain scale, designed for children 3 years of age and older, is useful in patients with whom communication may be difficult. The patient is asked to point to various facial expressions ranging from a smiling face (no pain) to an extremely unhappy one that expresses the worst possible pain. The VAS is a 10-cm horizontal line labeled “no pain” at one end and “worst pain imaginable” on the other end. The patient is asked to mark on this line where the intensity of the pain lies. The distance from “no pain” to the patient’s mark numerically quantifies the pain. The VAS is a simple and efficient method that correlates well with other reliable methods.

The MPQ is a checklist of words describing symptoms. Unlike other pain rating methods that assume pain is one-dimensional and describe intensity but not quality, the MPQ attempts to define the pain in three major dimensions: (1) sensory-discriminative (nociceptive pathways), (2) motivational-affective (reticular and limbic structures), and (3) cognitive-evaluative (cerebral cortex). It contains 20 sets of descriptive words that are divided into four major groups: 10 sensory, 5 affective, 1 evaluative, and 4 miscellaneous. The patient selects the sets that apply to his or her pain and circles the words in each set that best describe the pain. The words in each class are given rank according to severity of pain. A pain rating index is derived based on the words chosen.

Psychological Evaluation

The MMPI is a 566-item true-false questionnaire that attempts to define the patient’s personality on 10 clinical scales. Three validity scales serve to identify patients deliberately trying to hide traits or alter the results. Cultural differences can affect scores. Moreover, the test is lengthy and some patients find its questions insulting. The MMPI is used primarily to confirm clinical impressions about the role of psychological factors; it cannot reliably distinguish between “organic” and “functional” pain.

Depression is very common in patients with chronic pain. It is often difficult to determine the relative contribution of depression to the suffering associated with pain. The Beck Depression Inventory is a useful test for identifying patients with major depression.

Several tests have been developed to assess functional limitations or impairment (disability). These include the Multidimensional Pain Inventory (MPI), Medical Outcomes Survey 36-Item Short Form (SF-36), Pain Disability Index (PDI), and Oswestry Disability Index (ODI).

Emotional disorders are commonly associated with complaints of chronic pain, and chronic pain often results in varying degrees of psychological distress. Determination of which came first is often difficult. In either case, both the pain and emotional distress need to be treated. Table 47-7 lists emotional disorders in which treatment should be primarily directed at the emotional disorder.

Electromyography & Nerve Conduction Studies

Electromyography and nerve conduction studies complement one another and are useful for confirming the diagnosis of entrapment syndromes, radicular syndromes, neural trauma, and polyneuropathies. They can often distinguish between neurogenic and myogenic disorders. Patterns of abnormalities can localize a lesion to the spinal cord, nerve root, limb plexus, or peripheral nerve. In addition, they may also be useful in excluding “organic” disorders when psychogenic pain or a “functional” syndrome is suspected.

Electromyography employs needle electrodes to record potentials in individual muscles. Muscle potentials are recorded first while the muscle is at rest and then as the patient is asked to move the muscle. A triphasic motor unit action potential is normally seen as the patient voluntarily moves the muscle. Abnormal findings suggestive of denervation include persistent insertion potentials, the presence of positive sharp waves, fibrillary activity, or fasciculation potentials. Abnormalities in muscles produce changes in amplitude and duration as well as polyphasic action potentials.

Peripheral nerve conduction studies employ supramaximal stimulations of motor or mixed sensorimotor nerve, whereas muscle potentials are recorded over the appropriate muscle. The time between the onset of the stimulation and the onset of the muscle potential (latency) is a measurement of the fastest conducting motor fibers in the nerve. The amplitude of the recorded potential indicates the number of functional motor units, whereas its duration reflects the range of conduction velocities in the nerve. Conduction velocity can be obtained by stimulating the nerve from two points and comparing the latencies. When a pure sensory nerve is evaluated, the nerve is stimulated while action potentials are recorded either proximally or distally (antidromic conduction).

Nerve conduction studies distinguish between mononeuropathies (due to trauma, compression, or entrapment) and polyneuropathies. The latter include systemic disorders that may produce abnormalities that are widespread and symmetrical or that are random (eg, mononeuropathy multiplex).

Entrapment Syndromes

Neural compression may occur wherever a nerve courses through an anatomically narrowed passage, and entrapment neuropathies can involve sensory, motor, or mixed nerves. Genetic factors and repetitive macrotrauma or microtrauma are likely involved, and adjacent tenosynovitis is often responsible. Table 47-8 lists the most commonly recognized entrapment syndromes. When a sensory nerve is involved, patients complain of pain and numbness in its distribution distal to the site of entrapment; occasionally, a patient may complain of pain referred proximal to the site of entrapment. Entrapment of the sciatic nerve can mimic a herniated intervertebral disc. Entrapment of a motor nerve produces weakness in the muscles it innervates. Even entrapments of “pure” motor nerves can produce a vague pain that may be mediated by afferent fibers from muscles and joints. The diagnosis can usually be confirmed by electromyography and nerve conduction studies. Neural blockade of the nerve with local anesthetic, with or without corticosteroid, may be diagnostic and can provide temporary pain relief. Treatment is generally symptomatic with oral analgesics and temporary immobilization, whenever appropriate. Development of complex regional pain syndrome may respond to sympathetic blocks. Refractory symptoms may require surgical decompression.

Myofascial Pain

Gross trauma or repetitive microtrauma is thought to play a major role in initiating myofascial pain syndromes. Trigger points develop following acute injury; stimulation of these active trigger points produces pain, and the ensuing muscle spasm sustains the pain. When the acute episode subsides, the trigger points become latent (tender, but not pain producing) only to be reactivated at a later time by subsequent stress. The pathophysiology is poorly understood.

The diagnosis of a myofascial pain syndrome is suggested by the character of the pain and by palpation of discrete trigger points that reproduce it. Common syndromes produce trigger points in the levator scapulae, masseter, quadratus lumborum, and gluteus medius muscles. The latter two syndromes produce low back pain and should be considered in all patients with back pain; moreover, gluteal trigger points can mimic S1 radiculopathy.

Although myofascial pain may spontaneously resolve without sequelae, many patients continue to have latent trigger points. When trigger points are active, treatment is directed at regaining muscle length and elasticity. Analgesia may be provided utilizing local anesthetic (1-3 mL) trigger point injections. Topical cooling with either an ethyl chloride or fluorocarbon (fluoromethane) spray can also induce reflex muscle relaxation, facilitating massage (“stretch and spray”) and ultrasound therapy. Physical therapy is important in establishing and maintaining normal range of motion for affected muscles, and biofeedback may be helpful.

Fibromyalgia

The American College of Rheumatology recently identified three criteria that, if met, suggest the diagnosis of fibromyalgia:

1. Widespread Pain Index (WPI) score of 7 or higher, and Symptom Severity (SS) scale score of 5 or higher, or WPI of 3-6 and SS scale score of 9 or higher.

2. Symptoms present at a similar level for at least 3 months.

3. Absence of another disorder that would otherwise explain the pain.

Treatment of fibromyalgia includes cardiovascular conditioning, strength training, improving sleep hygiene, cognitive-behavioral therapy, patient education, and pharmacotherapy. Medications approved by the U.S. Food and Drug Administration (FDA) for the treatment of fibromyalgia include pregabalin (Lyrica), duloxetine (Cymbalta), and milnacipran (Savella).

Low Back Pain & Related Syndromes

Back pain is an extremely common complaint and a major cause of work disability worldwide. Lumbosacral strain, degenerative disc disease, and myofascial syndromes are the most common causes. Low back pain, with or without associated leg pain, may also have congenital, traumatic, degenerative, inflammatory, infectious, metabolic, psychological, and neoplastic causes. Moreover, back pain can be due to disease processes in the abdomen and pelvis, particularly those affecting retroperitoneal structures (pancreas, kidneys, ureters, and aorta), the uterus and adnexa, the prostate, and the rectosigmoid colon. Disorders of the hip can also mimic back disorders. A positive Patrick’s sign (or Patrick’s test)—ie, the elicitation of pain in the hip or sacroiliac joint when the examiner places the ipsilateral heel of the supine patient on the contralateral knee and presses down on the ipsilateral knee—helps identify back pain due to hip or sacroiliac joint disorders. This sign is also referred to by an acronym, FABERE (sign), because the movement of the leg involves flexion, abduction, external rotation, and extension.

Applied Anatomy of the Back

The back can be described in terms of anterior and posterior elements. The anterior elements consist of cylindrical vertebral bodies interconnected by intervertebral discs and supported by anterior and posterior longitudinal ligaments. The posterior elements are bony arches extending from each vertebral body, consisting of two pedicles, two transverse processes, two laminae, and a spinous process. The transverse and spinous processes provide points of attachment for the muscles that move and protect the spinal column. Adjacent vertebrae also articulate posteriorly by two gliding facet joints.

Spinal structures are innervated by the sinuvertebral branches and posterior rami of spinal nerves. The sinuvertebral nerve arises before each spinal nerve divides into anterior and posterior rami, and reenters the intervertebral foramen to innervate the posterior longitudinal ligament, the posterior annulus fibrosus, periosteum, dura, and epidural vessels. Paraspinal structures are supplied by the posterior primary ramus. Each facet joint is innervated by the medial branch of the posterior primary rami of the spinal nerves above and below the joint.

As lumbar spinal nerve roots exit the dural sac, they travel down 1-2 cm laterally before exiting through their respective intervertebral foramina; thus, for example, the L5 nerve root leaves the dural sac at the level of the L4-L5 disc (where it is more likely to be compressed) but leaves the spinal canal beneath the L5 pedicle opposite the L5-S1 disc.

Paravertebral Muscle & Lumbosacral Joint Sprain/Strain

Approximately 80-90% of low back pain is due to sprain or strain associated with lifting heavy objects, falls, or sudden abnormal movements of the spine. The term sprain is generally used when the pain is related to a well-defined acute injury, whereas strain is used when the pain is more chronic and is likely related to repetitive minor injuries.

Injury to paravertebral muscles and ligaments results in reflex muscle spasm, which may or may not be associated with trigger points. The pain is usually dull and aching, and occasionally radiates down the buttocks or hips. Sprain is a self-limited benign process that resolves in 1-2 weeks. Symptomatic treatment consists of rest and oral analgesics.

The sacroiliac joint is particularly vulnerable to rotational injuries. It is one of the largest joints in the body and functions to transfer weight from the upper body to the lower extremities. Acute or chronic injury can cause slippage, or subluxation, of the joint. Pain originating from this joint is characteristically located along the posterior ilium and radiates down the hips and posterior thigh to the knees. The diagnosis is suggested by tenderness on palpation, particularly on the medial aspect of the posterior superior iliac spine, and by compression of the joints. Pain relief following injection of the joint with local anesthetic (3 mL) is diagnostic and may also be therapeutic. Injection of intraarticular steroid medication may be considered. For potentially longer duration of analgesia, radiofrequency ablation may be performed at the dorsal ramus of L5 as well as the lateral branches of the S1, S2, and S3 nerves if the patient responded well to local anesthetic injections of the sacroiliac joint or to diagnostic injections of these nerves.

Buttock Pain

Buttock pain may be due to several different factors, and can be quite debilitating. Coccydynia (or, coccygodynia) may the result of trauma to the coccyx or surrounding ligaments. It may resolve by means of physical therapy, coccygeal nerve blocks to the lateral aspects of the coccyx, or ablative or neuromodulatory techniques. Piriformis syndrome presents as pain in the buttock, which can be accompanied by numbness and tingling in distribution of the sciatic nerve. The nerve may or may not be entrapped. Injection of local anesthetic into the belly of this muscle or into trigger points located at the origin and insertion of the muscle may help relieve the pain.

Degenerative Disc Disease

Intervertebral discs bear at least one third of the weight of the spinal column. Their central portion, the nucleus pulposus, is composed of gelatinous material early in life. This material degenerates and becomes fibrotic with advancing age and following trauma. The nucleus pulposus is ringed by the annulus fibrosus, which is thinnest posteriorly and bounded superiorly and inferiorly by cartilaginous plates. Disc (discogenic) pain may be due to one of two major mechanisms: (1) protrusion or extrusion of the nucleus pulposus posteriorly or (2) loss of disc height, resulting in the reactive formation of bony spurs (osteophytes) from the rims of the vertebral bodies above and below the disc. Degenerative disc disease most commonly affects the lumbar spine because it is subjected to the greatest motion and because the posterior longitudinal ligament is thinnest at L2-L5. Factors such as increased body weight and cigarette smoking may play a role in the development of lumbar disc disease. The role of the disc in producing chronic back pain is not clearly understood. In patients with persistent axial low back pain, the history and physical examination may provide clues. If the patient has pain when sitting or standing, or maintaining a certain position for an extended period of time, there may be an element of discogenic pain.

Discography is a procedure that is often used to try to provide some objective evidence of the role of a given disc in producing a patient’s back pain. After a needle is inserted into the disc, the opening pressure can be assessed; a subsequent injection of radiocontrast material produces increased pressure that may reproduce the patient’s pain and may provide radiographic identification of anatomic abnormalities within the disc (eg, a rent or tear). It the pain produced with injection is similar to that which the patient experiences on a daily basis, it is deemed concordant pain. If not, it is deemed discordant. In some circumstances, the pressure in the disc following injection is not significantly higher than the opening pressure. This may be due to the presence of a fissure in the disc that tracks to the epidural space. Risks of discography include infection and discitis, which may be difficult to treat because the disc is relatively avascular.

Treatment options for discogenic pain include conservative therapy, steroid injections into the disc, intradiscal biacplasty, involving heating the posterior annulus of the disc by way of radiofrequency ablation, and surgical fusion with bone graft or hardware placement; each has shown mixed degrees of success. The evaluation and treatment of discogenic pain is an area of significant controversy and ongoing research.

Herniated (Prolapsed) Intervertebral Disc

Weakness and degeneration of the annulus fibrosus and posterior longitudinal ligament can cause herniation of the nucleus pulposus posteriorly into the spinal canal.

Pain associated with disc disease is aggravated by bending, lifting, prolonged sitting, or anything that increases intraabdominal pressure, such as sneezing, coughing, or straining. It is usually relieved by lying down. Numbness or weakness is indicative of radiculopathy (Table 47-9). Bulging of the disc through the posterior longitudinal ligament can also produce low back pain that radiates to the hips or buttocks. Straight leg-raising tests may be used to assess nerve root compression. With the patient supine and the knee fully extended, the leg on the affected side is raised and the angle at which the pain develops is noted; dorsiflexion of the ankle with the leg raised typically exacerbates the pain by further stretching the lumbosacral plexus. Pain while raising the contralateral leg is an even more reliable sign of nerve compression.

The use of MRI has increased dramatically in the past decade in association with a two- to threefold increase in back surgeries, although this has not correlated with improved patient outcome. The American Pain Society’s clinical practice guidelines for low back pain do not recommend routine imaging or other diagnostic tests for patients with nonspecific low back pain. Up to 30-40% of asymptomatic persons have abnormalities of spinal structures on CT or MRI. In addition, the patient’s awareness of his or her imaging abnormalities may influence self-perception of health and functional ability.

Imaging studies and further tests should be acquired when severe or progressive neurological deficits are present, or when serious underlying conditions are suspected. CT myelography is the most sensitive test for evaluating subtle neural compression. Discography may be considered when the pain pattern does not match the clinical findings. A centrally herniated disc will usually cause pain at the lower level, and a laterally protruded disc will cause pain at the same level as the disc. For example, a centrally located disc herniation at L4-L5 may compress the L5 nerve root whereas a laterally located disc herniation at this level may compress the L4 nerve root.

The natural course of herniated disc disorders is generally benign and the duration of pain is usually less than 2 months. Over 75% of patients treated nonsurgically, even those with radiculopathy, have complete or near-complete pain relief. The goals of treatment should therefore be to alleviate the pain and rehabilitate the patient to return to a functional quality of life. Acute back pain due to a herniated disc can be initially managed with modification of activity and with medications such as NSAIDs and acetaminophen. A short course of opioids may be considered for patients with severe pain. After the acute symptoms subside, the patient can be referred to a physical therapist for instruction on exercises to improve lower back health. Patients who smoke tobacco should be advised to stop smoking, not only for the obvious health benefits but also because nicotine further compromises blood flow to the relatively avascular intervertebral disc. Percutaneous disc decompression involving extraction of a small amount of nucleus pulposus may help to decompress the nerve root. For patients with acute-onset weakness correlating with the level of the disc herniation, surgical management should be considered.

When symptoms persist beyond 3 months, the pain may be considered chronic and may require a multidisciplinary approach. Physical therapy continues to be a very important component of rehabilitation. NSAIDs and antidepressants are also helpful, and percutaneous interventions may be considered. Of note, back supports should be discouraged because they may weaken paraspinal muscles.

Spinal Stenosis

Spinal stenosis is a disease of advancing age. Degeneration of the nucleus pulposus reduces disc height and leads to osteophyte formation (spondylosis) at the endplates of adjoining vertebral bodies. In conjunction with facet joint hypertrophy and with ligamentum flavum hypertrophy and calcification, this process leads to progressive narrowing of the neural foramina and spinal canal. Neural compression may cause radiculopathy that mimics a herniated disc. Extensive osteophyte formation may compress multiple nerve roots and cause bilateral pain.

Patients with mild to moderate stenosis and radicular symptoms may obtain benefit from epidural steroid injections via a transforaminal, interlaminar, or caudal approach. This may help these individuals tolerate physical therapy. Those with moderate to severe stenosis may be amenable to more recently developed procedures, such as the minimally invasive lumbar decompression (MILD) procedure, which involves percutaneously sculpting the lamina and ligamentum flavum to reduce central canal compression. Severe multilevel symptoms may warrant surgical decompression.

Facet Syndrome

Degenerative changes in the facet (zygapophyseal) joints may also produce back pain. Pain may be near the midline; may radiate to the gluteal region, thigh, and knee; and may be associated with muscle spasm. Hyperextension and lateral rotation of the spine usually exacerbate the pain. The diagnosis may be confirmed if pain relief is obtained following intraarticular injection of local anesthetic solution into affected joints or by blockade of the medial branch of the posterior division (ramus) of the spinal nerves that innervate them. Long-term studies suggest that medial branch nerve blocks are more effective than facet joint injections. Medial branch rhizotomy may provide long-term analgesia for patients with facet joint disease.

Cervical Pain

Although most spine-related pain due to disc disease, spinal stenosis, or degenerative changes in the zygapophyseal joints is felt in the low back and lower extremities, patients may have cervical pain attributed to these processes. A key anatomic difference is that the cervical nerve roots, unlike those in the thoracic and lumbar spine, exit the foramina above the vertebral bodies for which they are named. This occurs until the level of C7, where the extra cervical nerve roots, C8, exit below the pedicles of C7, thus transitioning to the nomenclature of the thoracic- and lumbar-level vertebral bodies and nerve root denominations. The clinical examination may help to identify the nerve root that is affected with confirmation by a selective nerve root block. Risks inherent with percutaneous cervical procedures include accidental intravascular injection of local anesthetic or steroid. Particulate steroid injections in the neck have been associated with devastating outcomes such as spinal cord injury and death and should be avoided.

For primarily axial pain in the neck with extension into the head or to the shoulders, cervical medial branch blocks may clarify the diagnosis. Long-term analgesia may be obtained with radiofrequency ablation of the medial branches innervating the zygapophyseal joints.

Congenital Abnormalities

Congenital abnormalities of the back are often asymptomatic and remain occult for many years. Abnormal spinal mechanics can make the patient prone to back pain, and in some instances, progressive deformities. Relatively common anomalies include sacralization of L5 (the vertebral body is fused to the sacrum), lumbarization of S1 (it functions as a sixth lumbar vertebra), spondylolysis (a disruption of the pars interarticularis), spondylolisthesis (displacement anteriorly of one vertebral body on the next due to disruption of the posterior elements, usually the pars), and spondyloptosis (subluxation of one vertebral body on another resulting in one body in front of the next). The diagnosis is made radiographically. Spinal fusion may be necessary in patients with progressive symptoms and spinal instability.

Tumors

Benign primary tumors of the spine include hemangiomas, osteomas, aneurysmal bone cysts, and eosinophilic granulomas. Malignant spine tumors include osteosarcomas, Ewing’s sarcoma, and giant cell tumors. In addition, breast, lung, prostate, renal, gastrointestinal, and thyroid carcinomas, lymphomas, and multiple myelomas frequently metastasize to the lumbar spine. Pain is usually constant and may be associated with localized tenderness over involved vertebrae. Bony destruction, with or without neural or vascular compression, produces the pain. Intradural tumors such as meningiomas, schwannomas, ependymomas, and gliomas can present with a radiculopathy and may rapidly progress to flaccid paralysis. The primary site may be asymptomatic or difficult to localize, thus requiring imaging studies for diagnosis. Treatment options usually involve surgical decompression, chemotherapy, radiation therapy, and palliative symptom relief.

Infection

Bacterial infections of the spine usually begin as discitis before progressing to osteomyelitis, and can be due to pyogenic as well as tuberculous organisms. Patients may present with chronic back pain without fever or leukocytosis (eg, spinal tuberculosis). Those with acute discitis, osteomyelitis, or epidural abscess present with acute pain, fever, leukocytosis, elevated sedimentation rate, and elevated C-reactive protein, warranting immediate initiation of antibiotics. Urgent surgical intervention is indicated when the patient also suffers from acute weakness.

Arthritides

Ankylosing spondylitis is a familial disorder that is associated with histocompatibility antigen HLA-B27. It typically presents as low back pain associated with early morning stiffness in a young patient, usually male. The pain has an insidious onset and may initially improve with activity. After a few months to years, the pain gradually intensifies and is associated with progressively restricted movement of the spine. Diagnosis may be difficult early in the disease, but radiographic evidence of sacroiliitis is usually present. As the disease progresses, the spine develops a characteristic “bamboo-like” radiographic appearance. Some patients develop arthritis of the hips and shoulders, as well as extraarticular inflammatory manifestations. Treatment is primarily directed at functional preservation of posture. NSAIDs, particularly indomethacin, are effective analgesics that reduce the early morning stiffness. Anti-tumor necrosis factor-α agents have been shown to decrease the progression of ankylosing spondylitis when administered early in the course of therapy. These agents include infliximab (Remicaid), etanercept (Enbrel), adalimumab (Humira), and golimumab (Simponi). Although this treatment approach shows promise, patients may be at an increased risk for infection and the development of lymphoma.

Patients with Reiter’s syndrome, psoriatic arthritis, or inflammatory bowel disease may also present with low back pain, but extraspinal manifestations are usually more prominent. Rheumatoid arthritis usually spares the spine except for the zygapophyseal joints of the cervical spine.

Neuropathic Pain

Neuropathic pain includes pain associated with diabetic neuropathy, causalgia, phantom limbs, postherpetic neuralgia, stroke, spinal cord injury, and multiple sclerosis. Cancer pain and chronic low back pain may have prominent neuropathic components. Neuropathic pain tends to be paroxysmal and sometimes lancinating with a burning quality, and is usually associated with hyperpathia. Mechanisms of neuropathic pain are reviewed earlier in this chapter.

Because neuropathic pain is often difficult to treat, multiple therapeutic modalities may be necessary. Treatment options include anticonvulsants (eg, gabapentin, pregabalin), antidepressants (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors), antiarrhythmics (mexiletine), α2-adrenergic agonists (clonidine), topical agents (lidocaine or capsaicin), and analgesics (NSAIDs and opioids). Of note, tricyclic antidepressants may have significant anticholinergic side effects that may limit their tolerability. Secondary amines, such as nortriptyline or desipramine, may have less severe or fewer anticholinergic side effects than tertiary amines such as amitriptyline or imipramine. Spinal opioids may be very effective for some patients. Sympathetic blocks are effective in selected disorders (see below). Spinal cord stimulation may be effective for patients who do not tolerate or respond to other treatments.

Diabetic Neuropathy

The most common syndrome is peripheral polyneuropathy, which results in symmetric numbness (“stocking-and-glove” distribution), paresthesias, dysesthesias, and pain. The pain varies in intensity, may be severe, and is often worst at night. Loss of proprioception may lead to gait disturbances, and sensory deficits can lead to traumatic injuries. Isolated mononeuropathies affecting individual nerves may lead to wrist or foot drop or to cranial nerve palsy. Mononeuropathies typically have a sudden onset and are reversible, lasting a few weeks. Autonomic neuropathy typically affects the gastrointestinal tract, causing diarrhea, delayed gastric emptying, and esophageal motility disorders. Orthostatic hypotension and other forms of autonomic dysfunction are common.

Treatment of diabetic neuropathy is symptomatic and directed at optimal glycemic control to slow progression. Acetaminophen and NSAIDs are usually ineffective for moderate to severe pain. Risks associated with opioids limit their use in the treatment of this condition. Adjuvant drugs play a major role. The combination of an antiepileptic drug and a tricyclic antidepressant may be particularly effective.

Sympathetically Maintained & Sympathetically Independent Pain

CRPS is a largely underdiagnosed condition affecting at least 50,000 patients a year in the United States alone. It affects individuals from childhood to late adulthood and may occur more commonly in females. Patients frequently present with burning neuropathic pain having components of hyperalgesia and allodynia. The autonomic nervous system may be involved, exemplified by alterations in sweating (sudomotor changes), color, and skin temperature, and by trophic changes in the skin, hair, or nails. Decreases in strength and range of motion in the affected extremity may be present. CRPS may develop after minimal injury, although the most common initiating events are surgery, fractures, crush injuries, and sprains.

The pathophysiology of CRPS 1 and 2 is probably multifactorial, involving both the sympathetic nervous system and the central nervous system. There may be changes in the cutaneous innervation after a nerve injury, along with changes in central and peripheral sensitization. Genetic, inflammatory, and psychological factors may all play roles. Causalgia (which means burning pain), first identified in injured veterans of the American Civil War, typically follows gunshot injuries or other major trauma to large nerves. The pain often has an immediate onset and is associated with allodynia, hyperpathia, and vasomotor and sudomotor dysfunction. It is exacerbated by factors that increase sympathetic tone, such as fear, anxiety, light, noise, or touch. The syndrome has a variable duration that can range from days to months or may be permanent. Causalgia commonly affects the brachial plexus, particularly the median nerve, and the tibial division of the sciatic nerve in the lower extremity.

Patients with CRPS often respond to sympathetic blocks, but a multidisciplinary therapeutic approach must be utilized to avoid long-term functional and psychological disability. Some patients recover spontaneously, but if left untreated other patients can progress to severe and irreversible functional disability. Sympathetic blocks and intravenous regional sympatholytic blockade are equally effective; these blocks should be continued until either a cure is achieved or the response plateaus. The blocks facilitate physical therapy, which plays a central role and which typically consists of active movement without weights and of desensitization therapy. Many patients require a series of three to seven blocks. The likelihood of a cure is high (over 90%) if treatment is initiated within 1 month of symptom onset and appears to decrease over time with therapeutic delay.

Some patients benefit from transcutaneous electrical nerve stimulation (TENS) therapy. Spinal cord stimulation can be particularly effective in both acute and chronic settings. In the acute phase of treatment, there is increasing interest in placing tunneled epidural catheters for infusion therapy, or percutaneous electrodes for extended trials of spinal cord stimulation, in order to help patients tolerate physical therapy. Many patients benefit from surgical implantation of peripheral nerve stimulators placed directly on the larger injured nerves.

For sympathetically maintained pain, oral α-adrenergic blockers, such as the nonselective phenoxybenzamine or the α1-selective prazosin, may be beneficial. Caution is advised because of the risk of orthostatic hypotension with these agents, and dosage should be increased gradually. Anticonvulsant and antidepressant medications may also be beneficial.

Surgical sympathectomy in patients with chronic symptoms is frequently disappointing, resulting in only transient relief and in some cases a new, alternate pain syndrome. Recent research suggests that patients with pain refractory to prior medical or procedural therapies may respond to intravenous infusions of ketamine in a monitored setting.

Acute Herpes Zoster & Postherpetic Neuralgia

During an initial childhood infection (chickenpox), the varicella-zoster virus (VZV) infects dorsal root ganglia, where it remains latent until reactivation. Acute herpes zoster, which represents VZV reactivation, manifests as an erythematous vesicular rash in a dermatomal distribution that is usually associated with severe pain. Dermatomes T3-L3 are most commonly affected. The pain often precedes the rash by 48-72 h, and the rash usually lasts 1-2 weeks. Herpes zoster is most common in elderly and immunocompromised patients but may occur at any age. It is typically a self-limited disorder in younger, healthy patients (<50 years old). Treatment is primarily supportive, consisting of oral analgesics and oral acyclovir, famciclovir, ganciclovir, or valacyclovir. Antiviral therapy reduces the duration of the rash and speeds healing. Immunocompromised patients with disseminated infection (nondermatomal distribution of vesicles) require intravenous acyclovir therapy. Epidural steroid injections have not been proven to prevent postherpetic neuralgia (PHN).

Older patients may continue to experience severe, radicular pain from PHN even after the rash resolves. The incidence of PHN following acute herpes zoster is estimated to be 50% in patients older than 50 years of age. Moreover, PHN is often very difficult to treat. An oral course of corticosteroids during acute zoster may decrease the incidence of PHN but remains controversial and may increase the likelihood of viral dissemination in immunocompromised patients. Sympathetic blocks performed during the acute episode of herpes zoster often produce excellent analgesia and may decrease the incidence of PHN, although this is controversial. Some studies suggest that when sympathetic blocks are initiated within 2 months of the rash, PHN resolves in up to 80% of patients. Once the neuralgia is well established, however, sympathetic blocks, like other treatments, are generally ineffective. Antidepressants, anticonvulsants, opioids, and TENS may be useful in some patients. Tricyclic antidepressants may be particularly effective, though their use is often limited by anticholinergic side effects. Application of a transdermal lidocaine 5% patch (Lidoderm) over the most painful area may help relieve symptoms, presumably by decreasing peripheral sensitization of nerve endings and receptors. Application of capsaicin cream or a transdermal capsaicin 8% patch (Qutenza) may be helpful; however, Qutenza must be administered in a monitored setting. Administration of EMLA (euctectic mixture of local anesthetic) cream 1 h before application of the transdermal capsaicin patch may decrease the incidence and severity of pain from the capsaicin in the patch.

Headache

Headache is a common complaint that affects nearly everyone at some time in life. In the vast majority of cases, headaches do not reflect a serious underlying disorder and are not of sufficient severity or frequency for the individual to seek medical attention. However, as with other complaints of pain, the possibility of a clinically significant underlying disorder should always be considered. The practitioner should solicit other associated symptoms or clinical findings that suggest serious underlying pathology. Table 47-10 lists important causes of headache. Disorders in which the primary complaint is headache are considered in the following discussion. As will become apparent, there is significant variability in clinical presentation and overlap in the symptoms of the major headache syndromes, particularly between tension and migraine headaches.

Tension Headache

Tension headaches are classically described as tight bandlike pain or discomfort that is often associated with tightness in the neck muscles. The headache may be frontal, temporal, or occipital, more often bilateral than unilateral. Intensity typically builds gradually and fluctuates, lasting hours to days. They may be associated with emotional stress or depression. Treatment is symptomatic and consists of NSAIDs.

Migraine Headache

Migraine headaches are typically described as throbbing or pounding and are often associated with photophobia, scotoma, nausea and vomiting, and localized transient neurological dysfunction (aura). The latter may be sensory, motor, visual, or olfactory. Classic migraines by definition are preceded by an aura, whereas common migraines are not. The pain is usually unilateral but can be bilateral with a frontotemporal location and lasts 4-72 h. Migraines primarily affect children (both sexes equally) and young adults (predominantly females). A family history is often present. Provocation by odors, certain foods (eg, red wine), menses, and sleep deprivation is common. Sleep characteristically relieves the headache. The mechanism is complex and may include vasomotor, autonomic (serotonergic brainstem systems), and trigeminal nucleus dysfunction. Treatment is both abortive and prophylactic. Rapid abortive treatment includes oxygen, sumatriptan (6 mg subcutaneously), dihydroergotamine (1 mg intramuscularly or subcutaneously), intravenous lidocaine (100 mg), nasal butorphanol (1-2 mg), and sphenopalatine ganglion block. Other abortive options include zolmitriptan nasal spray, dihydroergotamine nasal spray, or an oral serotonin 5-HT1B/1D-receptor agonist (almotriptan, frovatriptan, naratriptan, rizatriptan, eletriptan, or sumatriptan). Prophylactic treatment may include β-adrenergic blockers, calcium channel blockers, valproic acid, amitriptyline, and onabotulinumtoxinA (Botox) injections.

Cluster Headache

Cluster headaches are classically unilateral and periorbital, occurring in clusters of one to three attacks a day over a 4- to 8-week period. The pain is described as a burning or drilling sensation that may awaken the patient from sleep. Each episode lasts 30-120 min. Remissions lasting a year at a time are common. Red eye, tearing, nasal stuffiness, ptosis, and Horner’s syndrome are classic findings. The headaches are typically episodic but can become chronic without remissions. Cluster headaches primarily affect males (90%). Abortive treatments includes oxygen and sphenopalatine block. Lithium, a short course of steroid medication, and verapamil may be used for prophylaxis.

Temporal Arteritis

Temporal arteritis is an inflammatory disorder of extracranial arteries. The headache can be bilateral or unilateral and is located in the temporal area in at least 50% of patients. The pain develops over a few hours, is usually dull in quality but may be lancinating at times and worse at night and in cold weather. Scalp tenderness is usually present. Temporal arteritis is often accompanied by polymyalgia rheumatica, fever, and weight loss. It is a relatively common disorder of older patients (>55 years), with an incidence of about 1 in 10,000 per year and a slight female predominance. Early diagnosis and treatment with steroids is important because progression can lead to blindness through involvement of the ophthalmic artery.

Trigeminal Neuralgia

Abdominal Pain

Chronic abdominal pain can have a variety of causes, and it is useful to distinguish between somatosensory, visceral, and centralized pain symptoms. A differential epidural block may help in elucidating the primary source but is time consuming and may be difficult to interpret. A transversus abdominis plane (TAP) blockade with ultrasound guidance may help treat somatosensory pain and thus may be potentially both diagnostic and therapeutic (see Chapter 46). The patient with pain of visceral origin may benefit from a celiac or splanchnic block.

Cancer-Related Pain

Cancer-related pain may be due to the cancerous lesion itself, metastatic disease, complications such as neural compression or infection, or treatment such as chemotherapy or radiation therapy. In addition, the cancer patient may have acute or chronic pain that is entirely unrelated to the cancer. The pain manager must therefore have a thorough understanding of the nature of the cancer, its stage, the presence of metastatic disease, and treatments.

Cancer pain can be managed with oral analgesics in most patients. The World Health Organization recommends a progressive, three-step approach: (1) nonopioid analgesics such as aspirin, acetaminophen, or NSAID for mild pain, (2) “weak” oral opioids (codeine and oxycodone) for moderate pain, and (3) stronger opioids (morphine and hydromorphone) for severe pain (Tables 47-11 and 47-12). Parenteral therapy is necessary when patients have refractory pain, cannot take medication orally, or have poor enteral absorption. Regardless of the agent selected, in most instances drug therapy should be provided on a fixed time schedule rather than as needed. Adjuvant drug therapy, particularly antidepressants, and other modalities should also be used liberally in patients with cancer-related pain (Table 47-13). Anticonvulsants may be useful (Table 47-14). Intrathecal drug delivery systems may improve analgesia and, via a drug-sparing effect, help decrease side effects associated with oral or intravenous agents. Numerous intrathecal agents have been studied, and opioids have been utilized both alone and in combination with other medications. Ziconotide is a direct-acting N-type calcium-channel blocker that may be helpful for refractory pain or as a first-line agent. It acts by decreasing the release of substance P from the presynaptic nerve terminal in the dorsal horn of the spinal cord. Side effects may be dose dependent and include auditory hallucinations and worsening of depression or psychosis. It does not lead to significant withdrawal conditions if abruptly discontinued.

Surgery, radiation therapy, and chemotherapy may prolong survivorship for patients with cancer. However, survivorship may be accompanied by therapy-related acute or chronic pain, including radiation fibrosis or chemotherapy-induced peripheral neuropathy. Treatment of these pain conditions is an area of ongoing research.

Interventional pain therapy may take the form of pharmacological treatment, nerve blocks with local anesthetics and steroid or a neurolytic solution, radiofrequency ablation, neuromodulatory techniques, or multidisciplinary treatment (psychological interventions, physical or occupational therapy, or modalities such as acupuncture).

Pharmacological Interventions

Pharmacological interventions in pain management include acetaminophen, cyclooxygenase (COX) inhibitors, opioids, antidepressants, neuroleptic agents, anticonvulsants, corticosteroids, and systemic administration of local anesthetics.

Acetaminophen

Acetaminophen (paracetamol) is an oral analgesic and antipyretic agent that recently has become available in the United States as an intravenous preparation (Ofirmev) for inpatient use. It inhibits prostaglandin synthesis but lacks significant antiinflammatory activity. Acetaminophen has few side effects but is hepatotoxic at high doses. The recommended adult maximum daily limit is 3000 mg/d, reduced from a previously recommended limit of 4000 mg/d. Isoniazid, zidovudine, and barbiturates can potentiate acetaminophen toxicity.

Nonsteroidal Antiinflammatory Drugs (NSAIDs)

Nonopioid oral analgesics include salicylates, acetaminophen, and NSAIDs (see Table 47-11). NSAIDs inhibit prostaglandin synthesis (COX). Prostaglandins sensitize and amplify nociceptive input, and blockade of their synthesis results in the analgesic, antipyretic, and antiinflammatory properties characteristic of NSAIDs. At least two types of COX are recognized. COX-1 is constitutive and widespread throughout the body, but COX-2 is expressed primarily with inflammation. Some types of pain, particularly pain that follows orthopedic and gynecological surgery, respond very well to COX inhibitors. COX inhibitors likely have important peripheral and central nervous system actions. Their analgesic action is limited by side effects and toxicity at higher doses. Selective COX-2 inhibitors, such as celecoxib, appear to have lower toxicity, particularly gastrointestinal side effects. Moreover, COX-2 inhibitors do not interfere with platelet aggregation. The COX-2 inhibitor rofecoxib increases the risk of cardiovascular complications; as a result, it has been taken off of the market in the United States.

All of the nonopioid oral analgesic agents are well absorbed enterally. Food delays absorption but otherwise has no effect on bioavailability. Because most of these agents are highly protein bound (>80%), they can displace other highly bound drugs such as warfarin. All undergo hepatic metabolism and are renally excreted. Dosages should therefore be reduced, or alternative medications selected, in patients with hepatic or renal impairment.

The most common side effects of aspirin (acetylsalicylic acid, ASA) and other NSAIDs are stomach upset, heartburn, nausea, and dyspepsia; some patients develop ulceration of the gastric mucosa, which appears to be due to inhibition of prostaglandin-mediated mucus and bicarbonate secretion. Diclofenac is available as both an oral preparation and a topical gel or patch that may be less likely to contribute to gastric distress.

Other side effects of NSAIDs include dizziness, headache, and drowsiness. With the exception of selective COX-2 inhibitors, all other COX inhibitors induce platelet dysfunction. Aspirin irreversibly acetylates platelets, inhibiting platelet adhesiveness for 1-2 weeks, whereas the antiplatelet effect of other NSAIDs is reversible and lasts approximately five elimination half-lives (24-96 h). This antiplatelet effect does not appear to appreciably increase the incidence of postoperative hemorrhage following most outpatient procedures. NSAIDs can exacerbate bronchospasm in patients with the triad of nasal polyps, rhinitis, and asthma. ASA should not be used in children with varicella or influenza infections because it may precipitate Reye’s syndrome. Lastly, NSAIDs can cause acute renal insufficiency and renal papillary necrosis, particularly in patients with underlying renal dysfunction.

Antidepressants

All antidepressant medications undergo extensive first-pass hepatic metabolism and are highly protein bound. Most are highly lipophilic and have large volumes of distribution. Elimination half-lives of most of these medications vary between 1 and 4 days, and many have active metabolites. Available agents differ in their side effects (see Table 47-13), which include antimuscarinic effects (dry mouth, impaired visual accommodation, urinary retention, and constipation), antihistaminic effects (sedation and increased gastric pH), α-adrenergic blockade (orthostatic hypotension), and a quinidine-like effect (atrioventricular block, QT prolongation, torsades de pointes).

Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs)

Milnacipran, along with the SNRI duloxetine and the anticonvulsant pregabalin, has also been approved in the United States by the FDA for the treatment of fibromyalgia. It has an elimination half-life of 8 h, is minimally metabolized by the liver, and is primarily excreted unchanged in the urine.

Duloxetine (Cymbalta) is useful in the treatment of neuropathic pain, depression, and fibromyalgia. It has a half-life of 12 h, is metabolized by the liver, and most of its metabolites are excreted in the urine.

Absolute and relative contraindications for the use of SNRIs include known hypersensitivity, usage of other drugs that act on the central nervous system (including monoamine oxidase inhibitors), hepatic and renal impairment, uncontrolled narrow-angle glaucoma, and suicidal ideation. Common side effects include nausea, headache, dizziness, constipation, insomnia, hyperhydrosis, hot flashes, vomiting, palpitations, dry mouth, and hypertension.

Neuroleptics

Neuroleptic medications may occasionally be useful for patients with refractory neuropathic pain, and may be most helpful in patients with marked agitation or psychotic symptoms. The most commonly used agents are fluphenazine, haloperidol, chlorpromazine, and perphenazine. Their therapeutic action appears to be due to blockade of dopaminergic receptors in mesolimbic sites. Unfortunately, the same action in nigrostriatal pathways can produce undesirable extrapyramidal side effects, such as masklike facies, a festinating gait, cogwheel rigidity, and bradykinesia. Some patients also develop acute dystonic reactions such as oculogyric crisis and torticollis. Long-term side effects include akathisia (extreme restlessness) and tardive dyskinesia (involuntary choreoathetoid movements of the tongue, lip smacking, and truncal instability). Like antidepressants, many of these drugs also have antihistaminic, antimuscarinic, and α-adrenergic-blocking effects.

Antispasmodics & Muscle Relaxants

Antispasmodics may be helpful for patients with musculoskeletal sprain and pain associated with spasm or contractures. Tizanidine (Zanaflex) is a centrally acting α2-adrenergic agonist used in the treatment of muscle spasm in conditions such as multiple sclerosis, low back pain, and spastic diplegia. Cyclobenzaprine (Flexeril) also may be effective for these conditions. Its precise mechanism of action is unknown.

Baclofen (Gablofen, Lioresal), a GABAB agonist, is particularly effective in the treatment of muscle spasm associated with multiple sclerosis or spinal cord injury when administered by continuous intrathecal drug infusion. Abrupt discontinuation of this medication has been associated with fever, altered mental status, pronounced muscle spasticity or rigidity, rhabdomyolysis, and death.

Corticosteroids

Glucocorticoids are extensively used in pain management for their antiinflammatory and possibly analgesic actions. They may be given topically, orally, or parenterally (intravenously, subcutaneously, intrabursally, intraarticularly, or epidurally). Table 47-15 lists the most commonly used agents, which differ in potency, relative glucocorticoid and mineralocorticoid activities, and duration or action. Large doses or prolonged administration result in significant side effects. Excess glucocorticoid activity can produce hypertension, hyperglycemia, increased susceptibility to infection, peptic ulcers, osteoporosis, aseptic necrosis of the femoral head, proximal myopathy, cataracts, and, rarely, psychosis. Patients with diabetes may have elevated blood glucose levels after corticosteroid injections. Patients can also develop the physical features characteristic of Cushing’s syndrome. Excess mineralocorticoid activity causes sodium retention and hypokalemia, and can precipitate congestive heart failure.

Many corticosteroid preparations are suspensions, rather than solutions, and the relative particulate size of a given glucocorticoid suspension may affect the risk of neural damage due to arterial occlusion when accidental arterial injection occurs. Because of the relatively small size of its suspension particles, dexamethasone is becoming the preferred corticosteroid for injection procedures involving relatively vascular areas, such as the head and neck region.

Anticonvulsants

Local Anesthetics

Systemic infusion of local anesthetic medication produces sedation and central analgesia and is occasionally used in the treatment of patients with neuropathic pain. The resultant analgesia may outlast the pharmacokinetic profile of the local anesthetic and break the “pain cycle.” Lidocaine, procaine, and chloroprocaine are the most commonly used agents. They are given either as a slow bolus or by continuous infusion. Lidocaine is given by infusion over 5-30 min for a total of 1-5 mg/kg. Procaine, 200-400 mg, can be given intravenously over the course of 1-2 h, whereas chloroprocaine (1% solution) is infused at a rate of 1 mg/kg/min for a total of 10-20 mg/kg. Monitoring by qualified medical personnel should include electrocardiographic data, blood pressure, respiration, pulse oximetry, and mental status, and full resuscitation equipment should be immediately available. Signs of toxicity, such as tinnitus, slurring of speech, excessive sedation, or nystagmus, necessitate slowing or discontinuing the infusion to avoid the progression to seizures.

Patients who do not respond satisfactorily to anticonvulsants but respond to intravenous local anesthetics may benefit from chronic oral antiarrhythmic therapy. Mexiletine (150-300 mg every 6-8 h) is a class 1B antiarrhythmic that is commonly used and generally well tolerated.

A 5% lidocaine transdermal patch (Lidoderm) containing 700 mg of lidocaine has been approved for the treatment of PHN. One to three patches may be applied to dry, intact skin, alternating 12 h on, then 12 h off. Topical lidocaine preparations, in concentrations up to 5%, may be helpful in the treatment of some neuropathic pain conditions.

α2-Adrenergic Agonists

The primary effect of α2-adrenergic agonists is activation of descending inhibitory pathways in the dorsal horn. Epidural and intrathecal α2-adrenergic agonists are particularly effective in the treatment of neuropathic pain and opioid tolerance. Clonidine (Catapres), a direct-acting α2-adrenergic agonist, is effective as an adjunctive medication in the treatment of severe pain. When administered orally, the dosage is 0.1-0.3 mg twice daily; a transdermal patch (0.1-0.3 mg/d) is also available and is usually applied for 7 d. When used in combination with a local anesthetic or opioid in an epidural or intrathecal infusion, clonidine may contribute to a synergistic or prolonged analgesic effect, especially for neuropathic pain.

Opioids

The most commonly prescribed oral opioid agents are codeine, oxycodone, and hydrocodone. They are easily absorbed, but hepatic first-pass metabolism limits systemic delivery. Like other opioids, they undergo hepatic biotransformation and conjugation before renal elimination. Codeine is transformed by the liver into morphine. The side effects of orally administered opioids are similar to those of systemic opioids. When prescribed on a fixed schedule, stool softeners or laxatives are often indicated. Tramadol (Rybix, Ryzolt, Ultram) is a synthetic oral opioid that also blocks neuronal reuptake of norepinephrine and serotonin. It appears to have the same efficacy as the combination of codeine and acetaminophen but, unlike others, it is associated with significantly less respiratory depression and has little effect on gastric emptying.

Moderate to severe cancer pain is usually treated with an immediate-release morphine preparation (eg, liquid morphine, Roxanol, 10-30 mg every 1-4 h). These preparations have an effective half-life of 2-4 h. Once the patient’s daily requirements are determined, the same dose can be given in the form of a sustained-release morphine preparation (MS Contin or Oramorph SR), which is dosed every 8-12 h. The immediate-release preparation is then used only for breakthrough pain (PRN). Oral transmucosal fentanyl lozenges (Actiq, 200-1600 mcg) can also be used for breakthrough pain. Excessive sedation can be treated with dextroamphetamine (Dexedrine, ProCentra) or methylphenidate (Ritalin), 5 mg in the morning and 5 mg the early afternoon. Most patients require a stool softener. Nausea may be treated with transdermal scopolamine, oral meclizine, or metoclopramide. Hydromorphone (Dilaudid) is an excellent alternative to morphine, particularly in elderly patients (because of fewer side effects) and in patients with impaired renal function. Methadone (Dolophine) is reported to have a half-life of 15-30 h, but clinical duration is shorter and quite variable (usually 6-8 h).

Tapentadol (Nucynta), a μ-opioid receptor agonist that also has norepinephrine reuptake inhibition properties, has recently been introduced for the management of acute and chronic pain. This opioid may be associated with less nausea and vomiting and less constipation. It should not be used concomitantly with monoamine oxidase inhibitors due to potentially elevated levels of norepinephrine.

Propoxyphene with and without acetaminophen (Darvocet and Darvon) was withdrawn from the U.S. market in 2010 due to the risk of cardiac toxicity.

Parenteral Opioid Administration

Intravenous, intraspinal (epidural or intrathecal), or transdermal routes of opioid administration must be utilized when the patient fails to adequately respond to, or is unable to tolerate, oral regimens. However, when the patient’s pain increases significantly, or changes markedly in quality, it is equally important to reevaluate the patient for adequacy of pain diagnosis and for the potential of disease progression. In patients with cancer, adjunctive treatments such as surgery, radiation, chemotherapy, hormonal therapy, and neurolysis may be helpful. Intramuscular opioid administration is rarely optimal because of variability in systemic absorption and resultant delay and variation in clinical effect.

Intravenous Opioid Therapy

Parenteral opioid therapy is usually best accomplished by intermittent or continuous intravenous infusion, or both, but can also be given subcutaneously. Modern portable infusion devices have patient-controlled analgesia (PCA) capability, allowing the patient to self-treat for breakthrough pain.

Spinal Opioid Therapy

The use of intraspinal opioids is an excellent alternative for patients obtaining poor relief with other analgesic techniques or who experience unacceptable side effects. Epidural and intrathecal opioids offer pain relief with substantially lower total doses of opioid and fewer side effects. Continuous infusion techniques reduce drug requirements (compared with intermittent boluses), minimize side effects, and decrease the likelihood of catheter occlusion. Myoclonic activity may be occasionally observed with intrathecal morphine or hydromorphone.

Epidural or intrathecal catheters can be placed percutaneously or implanted to provide long-term effective pain relief. Epidural catheters can be attached to lightweight external pumps that can be worn by ambulatory patients. A temporary catheter must be inserted first to assess the potential efficacy of the technique. Correct placement of the permanent catheter should be confirmed using fluoroscopy with contrast dye. Completely implantable intrathecal catheters with externally programmable pumps can also be used for continuous infusion (Figure 47-6). The reservoir of the implanted pump (Figure 47-7) is periodically refilled percutaneously. Implantable systems are most appropriate for patients with a life expectancy of several months or longer, whereas tunneled epidural catheters are appropriate for patients expected to live only weeks. Formation of an inflammatory mass (granuloma) at the tip of the intrathecal catheter can occur and may reduce efficacy.

The most frequently encountered problem associated with intrathecal opioids is tolerance. Generally a slow phenomenon, tolerance may develop rapidly in some patients. In such instances, adjuvant therapy must be used, including the intermittent use of local anesthetics or a mixture of opioids with local anesthetics (bupivacaine or ropivacaine 2-24 mg/d), clonidine (2-4 mcg/kg/h or 48-800 mcg/d, respectively), or the GABA agonist baclofen. Clonidine is particularly useful for neuropathic pain. In high doses, it is more likely to be associated with hypotension and bradycardia.

Complications of spinal opioid therapy include local skin infection, epidural abscess, meningitis, and death or permanent injury from pump programming or drug dilution errors. Superficial infections can be reduced by the use of a silver-impregnated cuff close to the exit site. Other complications of spinal opioid therapy include epidural hematoma, which may become clinically apparent either immediately following catheter placement or several days later, and respiratory depression. Respiratory depression secondary to spinal opioid overdose can be treated by decreasing the pump infusion rate to its lowest setting and initiating a naloxone intravenous infusion.

Transdermal Fentanyl

Transdermal fentanyl (Duragesic patch) is an alternative to sustained-release oral morphine and oxycodone preparations, particularly when oral medication is not possible. The currently available patches are constructed as a drug reservoir that is separated from the skin by a microporous rate-limiting membrane and an adhesive polymer. A very large quantity of fentanyl (10 mg) provides a large force for transdermal diffusion. Transdermal fentanyl patches are available in 25, 50, 75, and 100 mcg/h sizes that provide drug for 2-3 days. The largest patch is equivalent to 60 mg/d of intravenous morphine. The major obstacle to fentanyl absorption through the skin is the stratum corneum. Because the dermis acts as a secondary reservoir, fentanyl absorption continues for several hours after the patch is removed. The transdermal route avoids hepatic first-pass metabolism.

Major disadvantages of the transdermal route are its slow rate of drug delivery onset and the inability to rapidly change dosage in response to changing opioid requirements. Blood fentanyl levels rise and reach a plateau in 12-40 h, providing average concentrations of 1, 1.5, and 2 ng/mL for the 50, 75, and 100 mcg/h patches, respectively. Large inter-patient variability results in actual delivery rates ranging from 50 to 200 mcg/h. This formulation is popularly “diverted” for nonmedical uses and has been the cause of numerous deaths from “recreational” pharmacology.

Botulinum Toxin (Botox)

OnabotulinumtoxinA (Botox) injection has been increasingly utilized in the treatment of pain syndromes. Studies support its use in the treatment of conditions associated with involuntary muscle contraction (eg, focal dystonia and spasticity), and it is approved by the FDA for prophylactic treatment of chronic migraine headache. This toxin blocks acetylcholine released at the synapse in motor nerve endings but not sensory nerve fibers. Proposed mechanisms of analgesia include improved local blood flow, relief of muscle spasms, and release of muscular compression of nerve fibers

Procedural Therapy

Diagnostic & Therapeutic Blocks

Local anesthetic nerve blocks are useful in delineating pain mechanisms, and they play a major role in the management of patients with acute or chronic pain. Pain relief following diagnostic nerve blockade often carries favorable prognostic implications for a subsequent therapeutic series of blocks. Although the utility of differential nerve blocks in distinguishing between somatic and sympathetic mechanisms has been questioned, this technique can identify patients exhibiting a placebo response and those with psychogenic mechanisms. In selected patients, “permanent” neurolytic nerve blocks may be appropriate.

The efficacy of nerve blocks is presumably due to interruption of afferent nociceptive activity. This is in addition to, or in combination with, blockade of afferent and efferent limbs of abnormal reflex activity involving sympathetic nerve fibers and skeletal muscle innervation. The pain relief frequently outlasts (by hours up to several weeks) the known pharmacological duration of the agent employed. Selection of the type of block depends on the location of pain, its presumed mechanism, and the skills of the treating physician. Local anesthetic solutions may be applied locally (infiltration), or at a specific peripheral nerve, somatic plexus, sympathetic ganglia, or nerve root. The local anesthetic may also be applied centrally in the neuraxis.

Ultrasound-Guided Procedures

The use of ultrasound in interventional pain medicine has increased over the past decade due to its utility in visualizing vascular, neural, and other anatomic structures; its role as an alternative to the use of fluoroscopy and iodine-based contrast agents; and progressive improvements in technology leading to better visual images and greater simplicity of use. Most notably, ultrasound has become very useful for visualizing blood vessels and potentially decreasing the incidence of intravascular injection of particulate steroid medications. It may also be helpful in decreasing the risk of pneumothorax and of intraperitoneal injection. Procedures that may benefit from ultrasound guidance include trigger point injections, nerve blocks, and joint injections.

Fluoroscopy

Fluoroscopy is frequently used for interventional pain procedures. It is highly effective for visualizing bony structures and observing the spread of radiopaque contrast agents. Live fluoroscopy with contrast agent should be used to minimize the risk of intravascular injection of therapeutic agents. Care should be taken to avoid excessive use of fluoroscopy and to employ appropriate radiation shielding, given the risks of ionizing radiation to the patient and to the health care team members in the fluoroscopy suite.

Somatic Nerve Blocks

Trigeminal Nerve Block

Indications

The two principal indications for trigeminal nerve block are trigeminal neuralgia and intractable facial cancer pain. Depending on the site of pain, these blocks may be performed on the gasserian ganglion itself, on one of the major divisions (ophthalmic, maxillary, or mandibular), or on one of their smaller branches.

Anatomy

The rootlets of cranial nerve V arise from the brainstem and join one another to form a crescent-shaped sensory (gasserian) ganglion in Meckel’s cave. Most of the ganglion is invested with a dural sleeve. The three subdivisions of the trigeminal nerve arise from the ganglia and exit the cranium separately. (Figure 47-8A).

Technique

Gasserian Ganglion Block

Fluoroscopic guidance is mandatory for the performance of this procedure (Figure 47-8B). An 8- to 10-cm 22-gauge needle is inserted approximately 3 cm lateral to the angle of the mouth at the level of the upper second molar. The needle is then advanced posteromedially and angled superiorly to bring it into alignment with the pupil in the anterior plane and with the mid-zygomatic arch in the lateral plane. Without entering the mouth, the needle should pass between the mandibular ramus and the maxilla, and lateral to the pterygoid process to enter the cranium through the foramen ovale. After a negative aspiration for cerebrospinal fluid and blood, local anesthetic is injected.

Blocks of the Ophthalmic Nerve and Its Branches

In this procedure, to avoid denervation-related keratitis, only the supraorbital branch is blocked in most cases (Figure 47-8C); the ophthalmic division itself is not blocked. The nerve is easily located and blocked with local anesthetic at the supraorbital notch, which is located on the supraorbital ridge above the pupil. The supratrochlear branch can also be blocked with local anesthetic at the superior medial corner of the orbital ridge.

Blocks of the Maxillary Nerve and Its Branches

With the patient’s mouth slightly opened, an 8- to 10-cm 22-gauge needle is inserted between the zygomatic arch and the notch of the mandible (Figure 47-8D). After contact with the lateral pterygoid plate at about 4-cm depth (position 1 in figure), the needle is partially withdrawn and angled slightly superiorly and anteriorly to pass into the pterygopalatine fossa (position 2). Local anesthetic is injected once paresthesias are elicited. Both the maxillary nerve and the sphenopalatine (pterygopalatine) ganglia are usually anesthetized by this technique. The sphenopalatine ganglion (and anterior ethmoid nerves) can be anesthetized transmucosally with topical anesthetic applied through the nose; several cotton applicators soaked with local anesthetic (cocaine or lidocaine) are inserted along the medial wall of the nasal cavity into the area of the sphenopalatine recess. The sphenopalatine ganglion blockade may be helpful for patients with chronic nasal pain, cluster headache, or Sluder’s neuralgia.

The infraorbital branch of cranial nerve V passes through the infraorbital foramen, where it can be blocked with local anesthetic. This foramen is approximately 1 cm below the orbit and is usually located with a needle inserted about 2 cm lateral to the nasal ala and directed superiorly, posteriorly, and slightly laterally.

Blocks of the Mandibular Nerve and Its Branches

With the patient’s mouth slightly opened (Figure 47-8E), an 8 to10-cm 22-gauge needle is inserted between the zygomatic arch and the mandibular notch. After contact with the lateral pterygoid plate (position 1 in figure), the needle is partially withdrawn and angled slightly superiorly and posteriorly toward the ear (position 2). Local anesthetic is injected once paresthesias are elicited.

The lingual and inferior mandibular branches of the mandibular nerve may be blocked intraorally utilizing a 10-cm 22-gauge needle (Figure 47-8F). The patient is asked to open the mouth maximally and the coronoid notch is palpated with the index finger of the nonoperative hand. The needle is then introduced at the same level (approximately 1 cm above the surface of the last molar), medial to the finger but lateral to the pterygomandibular plica (position 1 in figure). It is advanced posteriorly 1.5-2 cm along the medial side of the mandibular ramus, making contact with the bone (position 2). Both nerves are usually blocked following injection of local anesthetic.

The terminal portion of the inferior alveolar nerve may be blocked as it emerges from the mental foramen at the mid-mandible just beneath the corner of the mouth. Local anesthetic is injected once paresthesias are elicited or the needle is felt to enter the foramen.

Complications

Complications of a gasserian ganglion block include accidental intravascular injection, subarachnoid injection, Horner’s syndrome, and motor block of the muscles of mastication. The potential for serious hemorrhage is greatest for blockade of the maxillary nerve. The facial nerve may be unintentionally blocked during blocks of the mandibular division.

Facial Nerve Block

Indications

Blockade of the facial nerve is occasionally indicated to relieve spastic contraction of the facial muscles, to treat herpes zoster involving the facial nerve, and to facilitate certain surgical procedures involving the eye.

Anatomy

The facial nerve can be blocked where it exits the cranium through the stylomastoid foramen. A small sensory component supplies special sensation (taste) to the anterior two thirds of the tongue and general sensation to the tympanic membrane, the external auditory meatus, soft palate, and part of the pharynx.

Technique

The entry point is just anterior to the mastoid process, beneath the external auditory meatus, and at the midpoint of the mandibular ramus. The nerve is approximately 1-2 cm deep and is blocked with local anesthetic just below the stylomastoid process.

Complications

If the needle is inserted too deeply past the level of the styloid bone, the glossopharyngeal and vagal nerves may also be blocked. Careful aspiration is necessary because of the proximity of the facial nerve to the carotid artery and the internal jugular vein.

Glossopharyngeal Block

Indications

Glossopharyngeal nerve block may be used for patients with pain due to cancer involving the base of the tongue, the epiglottis, or the palatine tonsils. It can also be used to distinguish glossopharyngeal neuralgia from trigeminal and geniculate neuralgia.

Anatomy

The nerve exits from the cranium via the jugular foramen medial to the styloid process and courses anteromedially to supply the posterior third of the tongue, pharyngeal muscles, and mucosa. The vagus and spinal accessory nerves also exit the cranium via the jugular foramen and descend alongside the glossopharyngeal nerve in close proximity to the internal jugular vein.

Technique

The block is performed using a 5-cm 22-gauge needle inserted just posterior to the angle of the mandible (Figure 47-9). The nerve is approximately 3-4 cm deep; therefore, use of a nerve stimulator facilitates correct placement of the needle. An alternative approach is from a point over the styloid process, midway between the mastoid process and the angle of the mandible; the nerve is located just anteriorly.

Complications

Complications include dysphagia and vagal blockade resulting in ipsilateral vocal cord paralysis and tachycardia. Block of the accessory nerve and hypoglossal nerves causes ipsilateral paralysis of the trapezius muscle and the tongue, respectively. Careful aspiration is necessary to prevent intravascular injection.

Occipital Nerve Block

Indications

Occipital nerve block is useful diagnostically and therapeutically in patients with occipital headaches and neuralgias.

Anatomy

The greater occipital nerve is derived from the dorsal primary rami of the C2 and C3 spinal nerves, whereas the lesser occipital nerve arises from the ventral rami of the same roots.

Technique

The greater occipital nerve is blocked approximately 3 cm lateral to the occipital prominence at the level of the superior nuchal line (Figure 47-10); the nerve is just medial to the occipital artery, which is often palpable. The lesser occipital nerve is blocked 2-3 cm more laterally along the nuchal ridge. Ultrasound guidance may be employed to help identify the nerves and minimize the risk of inadvertent intravenous or intraarterial injection. For patients who have responded well but temporarily to occipital nerve blocks, implantation of an occipital nerve stimulator may provide prolonged relief.

Complications

Rarely, intravascular injections may occur.

Suprascapular Nerve Block

Indications

This block is useful for painful conditions arising from the shoulder (most commonly arthritis and bursitis).

Anatomy

The suprascapular nerve is the major sensory nerve of the shoulder joint. It arises from the brachial plexus (C4-C6) and passes over the upper border of the scapula in the suprascapular notch to enter the suprascapular fossa.

Technique

The nerve is blocked at the suprascapular notch, which is located at the junction of the lateral and middle thirds of the superior scapular border (Figure 47-11). Correct placement of the needle is determined by paresthesia, ultrasound, or the use of a nerve stimulator.

Complications

Pneumothorax is possible if the needle is advanced too far anteriorly. Paralysis of the supraspinatus and infraspinatus muscles will result in impaired shoulder abduction.

Cervical Paravertebral Nerve Blocks

Indications

Cervical paravertebral nerve blocks can be useful diagnostically and therapeutically for patients with cervical disc displacement, cervical foraminal stenosis, or cancer-related pain originating from the cervical spine or shoulder.

Anatomy

The cervical spinal nerves lie in the sulcus of the transverse process of their respective vertebral levels. As noted earlier in this chapter, unlike thoracic and lumbar nerve roots, those in the cervical spine exit the foramina above the vertebral bodies for which they are named.

Technique

The lateral approach is most commonly used to block C2-C7 (Figure 47-12). Patients are asked to turn the head to the opposite side while in a sitting or supine position. A line is then drawn between the mastoid process and Chassaignac’s tubercle (the tubercle of the C6 transverse process). A series of injections are made with a 5-cm 22-gauge needle along a second parallel line 0.5 cm posterior to the first line. In the case of diagnostic blocks, a smaller injectate volume may be helpful in order to minimize local anesthetic spread to adjacent structures and thereby increase block specificity. Because the transverse process of C2 is usually difficult to palpate, the injection for this level is placed 1.5 cm beneath the mastoid process. The other transverse processes are usually interspaced 1.5 cm apart and are 2.5-3 cm deep. Fluoroscopy is useful in identifying specific vertebral levels during diagnostic blocks. This procedure may also be performed with ultrasound guidance.

Complications

Unintentional intrathecal or epidural anesthesia at this level rapidly causes respiratory paralysis and hypotension. Injection of even small volumes of local anesthetic into the vertebral artery causes unconsciousness and seizures. Other complications include Horner’s syndrome, as well as blockade of the recurrent laryngeal and phrenic nerves.

Embolic cerebrovascular and spinal cord complications have resulted from injection of particulate steroid with this block. Particulate steroid should not be used with cervical paravertebral nerve blocks because of possible anomalous vertebral artery anatomy in this region.

Thoracic Paravertebral Nerve Block

Indications

This technique may be used to block the upper thoracic segments, because the scapula interferes with the intercostal technique at these levels. Unlike an intercostal nerve block, a thoracic paravertebral nerve block anesthetizes both the dorsal and ventral rami of spinal nerves. It is therefore useful in patients with pain originating from the thoracic spine, thoracic cage, or abdominal wall, including compression fractures, proximal rib fractures, and acute herpes zoster. This block is also frequently utilized for intraoperative anesthesia and for postoperative pain management in breast surgery.

Anatomy

Each thoracic nerve root exits from the spinal canal just inferior to the transverse process of its corresponding spinal segment.

Technique

This block may be performed with the patient prone, lateral, or seated position. A 5- to 8-cm 22-gauge spinal needle with an adjustable marker (bead or rubber stopper) is used. With the classic technique, the needle is inserted 4-5 cm lateral to the midline at the spinous process of the level above. The needle is directed anteriorly and medially using a 45° angle with the mid-sagittal plane, and advanced until it contacts the transverse process of the desired level. The needle is then partially withdrawn and redirected to pass just under the transverse process. The adjustable marker on the needle is used to mark the depth of the spinous process; when the needle is subsequently withdrawn and redirected, it should not be advanced more than 2 cm beyond this mark. An alternative technique that may decrease the risk of pneumothorax uses a more medial insertion point and a loss-of-resistance technique very similar to epidural anesthesia. The needle is inserted in a sagittal plane 1.5 cm lateral to the midline at the level of the spinous process above and advanced until it contacts the lateral edge of the lamina of the level to be blocked. It is then withdrawn to a subcutaneous position and reinserted 0.5 cm more laterally but still in a sagittal plane. As the needle is advanced, it engages the superior costotransverse ligament, just lateral to the lamina and inferior to the transverse process. The correct position may be identified by loss of resistance to injection of saline when the needle penetrates the costotransverse ligament. Ultrasound guidance is helpful in performing this block (see Chapter 46).

Complications

The most common complication of paravertebral block is pneumothorax; accidental intrathecal, epidural, and intravascular injections may also occur. Sympathetic blockade and hypotension may be obtained if multiple segments are blocked or a large volume is injected at one level. A chest radiograph is mandatory if the patient exhibits signs or symptoms of pneumothorax.

Lumbar Paravertebral Nerve Blocks

Indications

Lumbar paravertebral nerve blocks may be useful in evaluating pain due to disorders involving the lumbar spine or spinal nerves.

Anatomy

The lumbar spinal nerves enter the psoas compartment as soon as they exit through the intervertebral foramina beneath the pedicles and transverse processes. This compartment is formed by the psoas fascia anteriorly, the quadratus lumborum fascia posteriorly, and the vertebral bodies medially.

Technique

The approach to lumbar spinal nerves is essentially the same as for thoracic paravertebral blockade (Figure 47-13). An 8-cm 22-gauge needle is usually used. Radiographic confirmation of the correct level is helpful. For diagnostic blocks, only 2 mL of local anesthetic is injected at any one level, because larger volumes may block more than one level. Larger volumes of local anesthetic are used for therapeutic blocks, or to produce complete somatic and sympathetic block of the lumbar nerves.

Complications

Complications are primarily those of unintentional intrathecal or epidural anesthesia. Patients may experience paresthesias if inadvertent nerve injury occurs during needle placement. Some physicians advocate the use of a blunt-tipped needle to (theoretically) decrease the chance of accidental intraneural injection. Digital subtraction angiography with radiopaque contrast may lessen the risk of intravascular injection of local anesthetic or steroid.

Cervical, Thoracic, & Lumbar Medial Branch Blocks

Indications

These blocks may be utilized in patients with back pain to assess the contribution of lumbar facet (zygapophyseal) joint disease. Corticosteroids are commonly injected with the local anesthetic when the intraarticular technique is chosen. The cervical, thoracic, or lumbar facet joints may be injected for diagnostic and potentially therapeutic purposes.

Anatomy

Each facet joint is innervated by the medial branches of the posterior primary division of the spinal nerves above and below the joint (Figure 47-14). Thus, every joint is supplied by two or more adjacent spinal nerves. Each medial branch crosses the upper border of the lower transverse process running in a groove between the root of the transverse process and the superior articular process.

Technique

These blocks are performed under fluoroscopic guidance with the patient in a prone position, or in some cases, the lateral position for cervical procedures. A posterior-anterior view facilitates visualization of the spine for lumbar medial branch blocks. A 10-cm 22-gauge needle is inserted 3-4 cm lateral to the spinous process at the desired level and directed anteriorly toward the junction of the transverse process and the superior articular process to block the medial branch of the posterior division of the spinal nerve (Figures 47-15, 47-16 and 47-17).

Alternatively, local anesthetic with or without corticosteroid may be directly injected into the facet joint. Positioning the patient prone and using an oblique fluoroscopic view facilitates identification of the joint space. Correct placement of the needle may be confirmed by injecting radiopaque contrast prior to injection of local anesthetic. Total injection volumes should ideally be limited to less than 1 mL in order to prevent rupture of the joint capsule.

Complications

Injection into a dural sleeve results in a subarachnoid block, whereas injection near the spinal nerve root results in sensory and motor block at that level. Because the joint normally has a small volume, larger injections can cause rupture of the joint capsule.

If a patient achieves improved pain control after a diagnostic block, he or she may be considered for radiofrequency ablation of the medial branch. There is debate about whether a second, confirmatory diagnostic block should be performed prior to radiofrequency ablation. Injection of steroid may be considered before or after radiofrequency ablation to theoretically decrease the chance for post-procedural neuritis.

Trans-Sacral Nerve Block

Indications

This technique is useful in the diagnosis and treatment of pelvic and perineal pain. In addition, blockade of the S1 spinal root can help define its role in back pain.

Anatomy

The five paired sacral spinal nerves and one pair of coccygeal nerves descend in the sacral canal. Each nerve then travels through its respective intervertebral foramen. The S5 and coccygeal nerves exit through the sacral hiatus.

Technique

While the patient is prone, the sacral foramina are identified with a needle along a line drawn 1.5 cm medial to the posterior superior iliac spine and 1.5 cm lateral to the ipsilateral sacral cornu (Figure 47-18). Correct positioning requires entry of the needle into the posterior sacral foramen and usually produces paresthesias. The S1 nerve root is usually 1.5 cm above the level of the posterior superior iliac spine along this imaginary line. Blockade of the S5 and coccygeal nerves can be accomplished by injection at the sacral hiatus.

Complications

Complications are rare but include nerve damage and intravascular injection.

Pudendal Nerve Block

Indications

Pudendal nerve block is useful in evaluating patients with perineal somatosensory pain.

Anatomy

The pudendal nerve arises from S2-S4 and courses between the sacrospinous and the sacrotuberous ligaments to reach the perineum.

Technique

This block is usually performed transperineally with the patient in the lithotomy position (Figure 47-19) although it may be performed via a posterior approach in the prone position. Injection of anesthetic is carried out percutaneously just posterior to the ischial spine at the attachment of the sacrospinous ligament. The ischial spine can be palpated transrectally or transvaginally. Alternatively, this procedure may be performed in the prone position with a 22-gauge needle directed toward the base of the ischial spine. Patients should be advised that they may have numbness of the genitalia for hours after this procedure is performed.

Complications

Potential complications include unintentional sciatic blockade and intravascular injection.

Sympathetic Nerve Blocks

Sympathetic blockade can be accomplished by a variety of techniques, including intrathecal, epidural, and paravertebral blocks. Unfortunately, these approaches usually block both somatic and sympathetic fibers. Problems with differential spinal and epidural techniques are discussed below. The following techniques specifically block sympathetic fibers and can be used to define the role of the sympathetic system in a patient’s pain and possibly also provide long-term pain relief. The most common indications for sympathetic nerve blocks include reflex sympathetic dystrophy, visceral pain, acute herpetic neuralgia, postherpetic pain, and peripheral vascular disease. Isolated sympathetic blockade to a region is characterized by loss of sympathetic tone, as evidenced by increased cutaneous blood flow and cutaneous temperature, and by unaltered somatic sensation. Other tests include loss of the skin conductance (sympathogalvanic reflex) and sweat response (ninhydrin, cobalt blue, or starch tests) following a painful stimulus.

Cervicothoracic (Stellate) Block

Indications

This block is often used for patients with head, neck, arm, and upper chest pain. It is commonly referred to as a stellate block but usually blocks the upper thoracic as well as all cervical ganglia. Injection of larger volumes of anesthetic often extends the block to the T5 ganglia. Stellate blocks may also be used for vasospastic disorders of the upper extremity.

Anatomy

Sympathetic innervation of the head, neck, and most of the arm is derived from four cervical ganglia, the largest being the stellate ganglion. The latter usually represents a fusion of the lower cervical and first thoracic ganglia. Some sympathetic innervation of the arm (T1) as well as innervation of all of the thoracic viscera derives from the five upper thoracic ganglia. The sympathetic supply to the arm in some persons may also originate from T2-T3 via anatomically distinct nerves (Kuntz’s nerves) that join the brachial plexus high in the axilla. These nerves may be missed by a stellate block but not an axillary block. The point of injection is at the level of the stellate, which lies posterior to the origin of the vertebral artery from the subclavian artery, anterior to the longus colli muscle and the first rib, anterolateral to the prevertebral fascia, and medial to the scalene muscles.

Technique

The paratracheal technique is most commonly used (Figure 47-20), although an oblique or posterior approach may also be taken. With the patient’s head extended, a 4- to 5-cm 22-gauge needle is inserted at the medial edge of the sternocleidomastoid muscle just below the level of the cricoid cartilage at the level of the transverse process of C6 (Chassaignac’s tubercle) or C7 (3-5 cm above the clavicle). The nonoperative hand should be used to retract the muscle together with the carotid sheath prior to needle insertion. The needle is advanced to the transverse process and withdrawn 2-3 mm prior to injection. Aspiration must be carried out in two planes before a 1-mL test dose is used to exclude unintentional intravascular injection into the vertebral or subclavian arteries or subarachnoid injection into a dural sleeve. A total of 5-10 mL of local anesthetic may be injected. Although this procedure is often performed under fluoroscopy, ultrasound may also be used to visualize the anatomy and decrease the risk of inadvertent intravascular injection.

Correct placement of the needle is usually followed promptly by an increase in the skin temperature of the ipsilateral arm and the onset of Horner’s syndrome. The latter consists of ipsilateral ptosis, meiosis, enophthalmos, nasal congestion, and anhydrosis of the neck and face. This may be considered a side effect of the block rather than a complication.

Complications

Thoracic Sympathetic Chain Block

The thoracic sympathetic ganglia lie just lateral to the vertebral bodies and anterior to the spinal nerve roots, but this block is generally not used because of a significant risk of pneumothorax.

Splanchnic Nerve Block

Three groups of splanchnic nerves (greater, lesser, and least) arise from the lower seven thoracic sympathetic ganglia on each side and descend alongside the vertebral bodies to communicate with the celiac ganglia. Although similar to celiac plexus block, the splanchnic nerve block may be preferred because it is less likely to block the lumbar sympathetic chain and because it requires less anesthetic.

The needle is inserted 6-7 cm from the midline at the lower end of the T11 spinous process, and advanced under fluoroscopic guidance to the anterolateral surface of T12. Ten milliliters of local anesthetic is injected on each side. The needle should maintain contact with the vertebral body at all times to avoid a pneumothorax. Other complications may include hypotension and possible injury to the azygos vein on the right or to the hemiazygos vein and the thoracic duct on the left.

If a patient’s pain lessens after a splanchnic nerve block, the procedure may be repeated to ensure that this result was not due to placebo effect. In addition, if the patient obtained pain relief from the initial block, he or she may subsequently benefit from radiofrequency ablation of the splanchnic nerves at T11 and T12, with potentially longer duration of analgesia. Performing the procedure on one side initially, and then the other side on a subsequent day, is advised due to the risk of pneumothorax.

Celiac Plexus Block

Indications

A celiac plexus block is indicated for patients with pain arising from the abdominal viscera, particularly intraabdominal cancers.

Anatomy

The celiac ganglia vary in number (1-5), form, and position. They are generally clustered at the level of the body of L1, posterior to the vena cava on the right, just lateral to the aorta on the left, and posterior to the pancreas.

Technique

The patient is placed in a prone position and a 15-cm 22-gauge needle is used to inject 15-20 mL of local anesthetic (Figure 47-21). Under fluoroscopic guidance, each needle is inserted 7-8 cm from the midline at the inferior edge of the spinous process of L1. It is advanced under radiographic guidance toward the midline, making an approximately 10-45° angle. The needle passes under the edge of the twelfth rib and should be positioned anterior to the body of L1 in the lateral radiographic view and close to the midline overlying the same vertebral body in the anteroposterior view. When CT guidance is used, the tip of the needle should come to lie anterolateral to the aorta at a level between the celiac and superior mesenteric arteries.

The celiac plexus block may be performed from multiple approaches including a posterior retrocrural approach, a posterior anterocrural approach, a posterior transaortic approach, and an anterior approach. These blocks may be facilitated with the use of fluoroscopy, CT, or ultrasound guidance.

Complications

The most common complication is postural hypotension, from block of the visceral sympathetic innervation and resultant vasodilation. For this reason, patients should be adequately hydrated intravenously prior to this block. Accidental intravascular injection into the vena cava is more likely to produce a severe systemic reaction than accidental intraaortic injection. Other, less common, complications include pneumothorax, retroperitoneal hemorrhage, injury to the kidneys or pancreas, sexual dysfunction, or, rarely, paraplegia (due to injury to the lumbar artery of Adamkiewicz). Blocking the sympathetic chain may result in relatively unopposed parasympathetic activity that may lead to increased gastrointestinal motility and diarrhea. Back pain is another common side effect of a celiac plexus block.

Lumbar Sympathetic Block

Indications

Lumbar sympathetic block may be indicated for painful conditions involving the pelvis or the lower extremities, and possibly for some patients with peripheral vascular disease.

Anatomy

The lumbar sympathetic chain contains three to five ganglia and is a continuation of the thoracic chain. It also supplies sympathetic fibers to the pelvic plexus and ganglia. The lumbar sympathetic chain ganglia are in a more anteromedial position to the vertebral bodies than the thoracic ganglia, and are anterior to the psoas muscle and fascia. The lumbar chain is usually posterior to the vena cava on the right but is just lateral to the aorta on the left.

Technique

A single-needle technique at the L3 level on either side is most commonly employed with the patient either prone or in a lateral position (Figure 47-22). The needle is inserted at the upper edge of the spinous process and is directed above or just lateral to the transverse process of the vertebrae (depending on the distance from the midline). Fluoroscopic guidance with injection of radiopaque contrast prior to local anesthetic injection is often used.

Complications

Complications include intravascular injection into the vena cava, aorta, or lumbar vessels and somatic nerve block of the lumbar plexus. In particular, the genitofemoral nerve may be blocked.

Superior Hypogastric Plexus Block

Indications

This procedure is indicated for pain that originates from the pelvis and is unresponsive to lumbar or caudal epidural blocks. The hypogastric plexus contains visceral sensory fibers that bypass the lower spinal cord. This block is usually appropriate for patients with cancer of the cervix, uterus, bladder, prostate, or rectum. It may also be effective in some women with chronic noncancer pelvic pain.

Anatomy

The hypogastric plexus contains not only postganglionic fibers derived from the lumbar sympathetic chain, but also visceral sensory fibers from the cervix, uterus, bladder, prostate, and rectum. The superior hypogastric plexus usually lies just to the left of the midline at the L5 vertebral body and beneath the bifurcation of the aorta. The fibers of this plexus divide into left and right branches and descend to the pelvic organs via the left and right inferior hypogastric and pelvic plexuses. The inferior hypogastric plexus additionally receives preganglionic parasympathetic fibers from the S2-S4 spinal nerve roots.

Technique

The patient is positioned prone, and a 15-cm needle is inserted approximately 7 cm lateral to the L4-L5 spinal interspace. The needle is directed medially and caudally under fluoroscopic guidance so that it passes by the transverse process of L5. In its final position, the needle should lie anterior to the intervertebral disc between L5 and S1 and within 1 cm of the vertebral bodies in the anteroposterior view. Injection of radiopaque contrast confirms correct position of the needle in the retroperitoneal space; 8-10 mL of local anesthetic is then injected. The superior hypogastric plexus block may also be performed using a transdiscal approach, though there is a risk of discitis associated with this procedure.

Complications

Complications include intravascular injection and transient bowel and bladder dysfunction.

Ganglion Impar Block

Indications

Anatomy

The ganglion impar (ganglion of Walther) is the most caudal part of the sympathetic trunks. The two lowest pelvic sympathetic ganglia often fuse forming one ganglion in the midline just anterior to the coccyx.

Technique

The patient may be positioned in the prone, lateral decubitus, or lithotomy position. A 22-gauge needle is advanced through the sacrococcygeal ligament and the rudimentary disc into a position just anterior to the coccyx. This procedure can be facilitated with fluoroscopy or ultrasound. Radiofrequency ablation, or in some cases a neurolytic injection, may provide longer duration of analgesia for this sympathetically mediated pain.

Complications

Intravascular injection and transient bowel or bladder dysfunction are possible. Alternative approaches involve placement of the needle through the anococcygeal ligament, although these may have higher potential to perforate the rectum.

Intravenous Regional Block

A Bier block (see Chapter 46) utilizing local anesthetic solution with or without adjuvants can be used to interrupt sympathetic innervation to an extremity. A total volume of 50 mL of 0.5% lidocaine is typically injected, either alone or in combination with clonidine (150 mcg) and in some cases ketorolac (15-30 mg). A tourniquet is placed proximally on the extremity, which is then elevated and exsanguinated using an Esmarch bandage. The tourniquet is inflated to a pressure that is two times the systolic blood pressure, the Esmarch bandage is removed, and the limb is checked to be certain the pulse is absent and there is no evidence of blood flow. The solution is then injected and usually left in place for at least 30 min, after which the tourniquet is released incrementally and the patient is observed for any signs or symptoms of local anesthetic toxicity. Premature release of the tourniquet may result in seizure, hypotension, arrhythmia, edema, diarrhea, and nausea. Intravenous regional sympathetic block is a safe alternative to standard sympathetic blocks in patients with hemostatic defects.

Epidural Injections

Epidural steroid injections (Figure 47-23) are used for symptomatic relief of pain associated with nerve root compression (radiculopathy). Pathological studies often demonstrate inflammation following disc herniation. Clinical improvement appears to be correlated with the resolution of nerve root edema. Epidural steroid injections are clearly superior to local anesthetics alone. They are most effective when given within 2 weeks of pain onset but appear to be of little benefit in the absence of neural compression or irritation. Long-term studies have failed to show any persistent benefit after 3 months, and these injections may change the time course of pain relief without changing long-term outcomes.

The two most commonly used agents are methylprednisolone acetate (40-80 mg) and triamcinolone diacetate (40-80 mg). Dexamethasone is being used with increased frequency due to its smaller particulate size (smaller than an erythrocyte). Intravascular injection of steroid suspension with larger particulate size may lead to embolic complications. The steroid may be injected with diluent (saline) or local anesthetic in volumes of 6-10 mL or 10-20 mL for lumbar and caudal injections, respectively. Simultaneous injection of opioids offers no added benefit and may significantly increase risks. The epidural needle should be cleared of the steroid prior to its withdrawal to prevent formation of a fistula tract or skin discoloration. Injection of local anesthetic along with the steroid can be helpful if the patient has significant muscle spasm, but it is associated with risks of intrathecal, subdural, and intravascular injection. The presenting pain is often transiently intensified following injection, and the local anesthetic provides immediate pain relief until the steroidal antiinflammatory effects take place, usually within 12-48 h.

Epidural steroid injections may be most effective when the injection is at the site of injury. Only a single injection is given if complete pain relief is achieved. If there is a good but temporary response, a second injection may be given 2-4 weeks later. Larger or more frequent doses increase the risk of adrenal suppression and systemic side effects. Most pain practitioners utilize fluoroscopy for epidural injection and confirm correct placement with injection of radiopaque contrast (Figures 47-24, 47-25 and 47-26). A transforaminal epidural steroid injection may be more effective than the standard interlaminar epidural technique, especially for radicular pain. The needle is directed under fluoroscopic guidance into the foramen of the affected nerve root; contrast is then injected to confirm spread into the epidural space and absence of intravascular injection prior to steroid injection. This technique differs from a selective nerve root block (SNRB) in two important ways; with an SNRB, the needle does not enter the foramen and the injected solution tracks along the nerve but not into the epidural space. The SNRB may be helpful as a diagnostic procedure for the surgeon who is considering a foraminotomy at a particular affected level based upon imaging, clinical presentation, and the results of the SNRB.

Caudal injection may be used in patients with previous back surgery when scarring and anatomic distortion make lumbar epidural injections more difficult. Unfortunately, migration of the steroid to the site of injury may not be optimal. The use of a catheter to direct the injection within the sacral and epidural canal may improve outcome. However, above the level of S2, there is a risk of thecal perforation with a stylet-guided catheter. Intrathecal steroid injections are not recommended because the ethylene glycol preservative in the suspension has been implicated in arachnoiditis following unintentional subarachnoid injections.

Radiofrequency Ablation & Cryoneurolysis

Percutaneous radiofrequency ablation (RFA) relies on the heat produced by current flow from an active electrode that is incorporated at the tip of a special needle. The needle is positioned using fluoroscopic guidance. Electrical stimulation (2 Hz for motor responses, 50 Hz for sensory responses) and impedance measurement via the electrode prior to ablation also help confirm correct electrode positioning. Depending on the location of the block, the heating temperature generated at the electrode is precisely controlled (60-90°C for 1-3 min) to ablate the nerve without causing excessive collateral tissue damage. RFA is commonly used for trigeminal rhizotomy and medial branch (facet) rhizotomy. It has also been used for dorsal root rhizotomy and lumbar sympathectomy. Pain relief is usually limited to 3-12 months due to nerve regeneration after RFA. This may be effective for medial branches of the spinal nerves that innervate facet joints. The lesion from thermal RFA is typically ovoid in shape and dependent upon factors such as the gauge of the needle, the temperature of the needle tip, and the duration of the heating procedure. Cooling the RFA needle with a sterile water system may decrease the charring associated with thermal lesioning and extend the spread of the lesion while heating at lower temperatures. Pulsed radiofrequency at 42°C is also being evaluated for various pain conditions.

Cryoanalgesia may produce temporary neurolysis for weeks to months by freezing and thawing tissue. The temperature at the tip of a cryoprobe rapidly drops as gas (carbon dioxide or nitrous oxide) at a high pressure is allowed to expand. The probe tip, which can achieve temperatures of -50°C to -70°C, is introduced via a 12- to 16-gauge catheter. Electrical stimulation (2-5 Hz for motor responses and 50-100 Hz for sensory responses) helps confirm correct positioning of the probe. Two or more 2-min cycles of freezing and thawing are usually administered. Cryoanalgesia is most commonly used to achieve long-term blockade of peripheral nerves. It may be particularly useful for post-thoracotomy pain. Patients often have neuropathic pain following thoracotomy or similar surgery. Diagnostic intercostal nerve blocks may be helpful to identify the nerve(s) that may be contributing to chronic thoracic or abdominal pain, and intercostal nerve blocks may also be utilized for longer term analgesia. The principal risks of intercostal nerve blocks are pneumothorax and local anesthetic toxicity. RFA of the intercostal nerves may be helpful as a palliative therapy for intercostal neuralgia, although there is a risk of deafferentation pain after this procedure.

Chemical Neurolysis

Temporary destruction of nerve fibers or ganglia can be accomplished by injection of alcohol or phenol. These neurolytic agents are not selective, affecting visceral, sensory, and motor fibers equally. Ethyl alcohol (50-100%) causes extraction of membrane phospholipids and precipitation of lipoproteins in axons and Schwann cells, whereas phenol (6-12%) appears to coagulate proteins. Alcohol causes severe pain on injection, thus local anesthetic is usually administered first. For peripheral nerve blocks, alcohol may be given undiluted, but for sympathetic blocks in which large volumes are injected, it is given in a 1:1 mixture with bupivacaine. Phenol is usually painless when injected either as an aqueous solution (6-8%) or in glycerol; a 12% phenol solution can be prepared in radiopaque contrast solution.

Neurolytic Techniques

Neurolytic celiac plexus or splanchnic nerve blocks may be effective for painful intraabdominal neoplasms, especially pancreatic cancer. Lumbar sympathetic, hypogastric plexus, or ganglion impar neurolytic blocks can be used for pain secondary to pelvic neoplasms. Neurolytic saddle block can provide pain relief for patients with refractory pain from pelvic malignancy; however, bowel and bladder dysfunction should be expected. Neurolytic intercostal blocks can be helpful for patients with painful rib metastases. Additional neurodestructive procedures, such as pituitary adenolysis and cordotomy, may be useful in end-of-life palliative care.

When considering any neurolytic technique, at least one diagnostic block with a local anesthetic solution alone should be used initially to confirm the pain pathway(s) involved and to assess the potential efficacy of the planned neurolysis. Local anesthetic solution should again be injected immediately prior to the neurolytic agent under fluoroscopic guidance. Following injection of any neurolytic agent, the needle must be cleared with air or saline prior to withdrawal to prevent damage to superficial structures.

Many clinicians prefer alcohol for celiac plexus block and phenol for lumbar sympathetic block. For subarachnoid neurolytic techniques, very small amounts of neurolytic agent (0.1 mL) are injected. Alcohol is hypobaric, whereas phenol in glycerin is hyperbaric; the patient undergoing subarachnoid neurolysis is carefully positioned so that the solution travels to the appropriate level and is confined to the dorsal horn region following subarachnoid administration.

Cancer patients frequently receive anticoagulation therapy if they are at elevated risk for venous thromboembolic phenomena. When such a patient has discontinued anticoagulant medication in preparation for a diagnostic local anesthetic block, it may be more practical to obtain consent for a neurolytic procedure in advance and to follow the diagnostic block immediately with chemical neurolysis if the diagnostic procedure has resulted in pain relief.

Differential Neural Blockade

Pharmacological or anatomic differential neural blockade has been advocated as a method of distinguishing somatic, sympathetic, and psychogenic pain mechanisms. The procedure is controversial owing to the challenges of interpreting the data and the inability to define exactly which nerve fibers or pathways are blocked. Theoretically, the pharmacological approach relies on the differential sensitivity of nerve fibers to local anesthetics. Preganglionic sympathetic (B) fibers are reported to be most sensitive, closely followed by pain (Aδ) fibers, somatosensory (Aβ) fibers, motor fibers (Aα), and finally C fibers. By using different concentrations of local anesthetic, it may be possible to selectively block certain types of fibers while preserving the function of others. The challenge is that the critical concentration needed to block sympathetic fibers can vary considerably between patients, and conduction block by local anesthetics is dependent not only on fiber size but also on the duration of contact and frequency of impulses conducted. Many clinicians have therefore abandoned the use of pharmacological differential neural blocks in favor of anatomic differential blockade.

Stellate ganglion blocks can be used to selectively block sympathetic fibers to the head, neck, and arm. Celiac plexus, hypogastric plexus, and lumbar paravertebral sympathetic blocks can be used for sympathetic blocks of the abdomen, pelvis, and leg, respectively. Selective nerve root, intercostal, cervical plexus, brachial plexus, or lumbosacral plexus blocks may be used for somatic nerve blockade.

Differential epidural blocks may be used for thoracic pain when the techniques for sympathetic blockade carry a significant risk of pneumothorax (Table 47-16). After each epidural injection, the patient is evaluated for pain relief, signs of sympathetic blockade (a decrease in blood pressure), sensation to pinprick and light touch, and motor function. If the pain disappears after the saline injection, the patient either has psychogenic pain (usually a profound long-lasting effect) or is displaying a placebo effect (usually short lasting). If pain relief coincides with isolated signs of sympathetic blockade, it is likely mediated by sympathetic fibers. If pain relief only follows somatosensory blockade, it is likely mediated by somatic fibers. Lastly, if the pain persists even after signs of motor blockade, the pain is either central (supraspinal) or psychogenic.

The differential epidural block carries the risk of any neuraxial block, and the possibility of hypotension and blocking cardiac accelerator fibers at T1-T4. The level should not extend above the T5 dermatome due to these risks. Following catheter insertion, injections should be administered with the patient in a monitored setting for the rest of this procedure.

Although differential epidural blockade has limitations, it may be helpful to identify primarily centralized pain when a patient continues to have a significant level of pain despite multilevel dermatomal blockade over the painful region. It is unlikely that a subsequent nerve block would help to treat the painful condition.

When it is thought that a patient may have abdominal pain from the anterior abdominal wall, a transversus abdominis plane (TAP) block may be performed using ultrasound guidance. This may offer potential short- or long-term relief and can be considered as an alternative to differential epidural blockade. If no relief is obtained, the pain may have a visceral origin or a central cause. Visceral pain may best respond to a celiac or splanchnic nerve block and possibly to subsequent splanchnic RFA. Patients with pain that is primarily of a central origin may respond to multidisciplinary therapy, including counseling and biofeedback training.

Neuromodulation

Electrical stimulation of the nervous system can produce analgesia in patients with acute and chronic pain. Current may be applied transcutaneously, epidurally, or by electrodes implanted into the central nervous system.

Transcutaneous Electrical Nerve Stimulation

Transcutaneous electrical nerve stimulation (TENS) is thought to produce analgesia by stimulating large afferent fibers. It may have a role for patients with mild to moderate acute pain and those with chronic low back pain, arthritis, and neuropathic pain. The gate theory of pain processing suggests that the afferent input from large epicritic fibers competes with that from the smaller pain fibers. An alternative theory proposes that at high rates of stimulation, TENS causes conduction block in small afferent pain fibers. With conventional TENS, electrodes are applied to the same dermatome as the pain and are stimulated periodically by direct current from a generator (usually for 30 min several times a day). A current of 10-30 mA with a pulse width of 50-80 μs is applied at a frequency of 80-100 Hz. Some patients whose pain is refractory to conventional TENS respond to low-frequency TENS (acupuncture-like TENS), which employs stimuli with a pulse width greater than 200 μs at frequencies less than 10 Hz (for 5-15 min). Unlike conventional TENS, low-frequency stimulation is at least partly reversed by naloxone, suggesting a role for endogenous opioids. This technique is also called dorsal column stimulation because it was thought to produce analgesia by directly stimulating large Aβ fibers in the dorsal columns of the spinal cord. Proposed mechanisms include activation of descending modulating systems and inhibition of sympathetic outflow.

Spinal Cord Stimulation

Temporary electrodes are initially placed in the posterior epidural space and connected to an external generator to evaluate efficacy in a 5- to 7-day trial (Figures 47-27 and 47-28). The trial may be extended, particularly if it allows a patient, such as one with CRPS, to tolerate more aggressive physical therapy. If a favorable response is obtained, a fully implantable system is inserted. Unfortunately, the effectiveness of the technique decreases with time in some patients. Complications include infection, lead migration, and lead breakage.

Peripheral Nerve Stimulation

Peripheral nerve stimulation (PNS) differs from SCS in that leads are placed in close anatomic proximity to an injured peripheral nerve. The leads may be placed percutaneously, with or without ultrasound guidance, or surgically under direct vision of the nerve. Occipital nerve stimulators are one form of peripheral nerve stimulator that may be helpful in treating occipital neuralgia and migraine headache (Figure 47-29).

Deep Brain Stimulation

Deep brain stimulation (DBS) is used for intractable cancer pain and for intractable nonmalignant neuropathic pain. Electrodes are implanted stereotactically into the periaqueductal and periventricular gray areas for nociceptive pain, usually in patients with cancer or chronic low back pain. For neuropathic pain, the electrodes are frequently implanted into the ventral posterolateral and ventral posteromedial thalamic nuclei. DBS may also be helpful for patients with movement disorders, headache, and neuropsychiatric disorders. The most serious complications are intracranial hemorrhage and infection.

Vertebral Augmentation

Multidisciplinary Treatment

Psychological Interventions

Psychological techniques, including cognitive therapy, behavioral therapy, biofeedback, relaxation techniques, and hypnosis, are most effective when employed by psychologists or psychiatrists. Cognitive interventions are based on the assumption that a patient’s attitude toward pain can influence the perception of pain. Maladaptive attitudes contribute to suffering and disability. The patient is taught skills for coping with pain either individually or in group therapy. The most common techniques include attention diversion and imagery. Behavioral (operant) therapy is based on the premise that behavior in patients with chronic pain is determined by consequences of the behavior. Positive reinforcers (such as attention from a spouse) tend to enable or intensify the pain, whereas negative reinforcers reduce pain. The therapist’s role is to guide behavior modification with the aid of family members and medical providers in order to nurture negative reinforcers and minimize positive reinforcers.

Relaxation techniques teach the patient to alter the arousal response and the increase in sympathetic tone associated with pain. The most commonly employed technique is a progressive muscle relaxation exercise. Biofeedback and hypnosis are closely related interventions. All forms of biofeedback are based on the principle that patients can be taught to control involuntary physiological parameters. Once proficient in the technique, the patient may be able induce a relaxation response and more effectively apply coping skills to control physiological factors (eg, muscle tension) that worsen pain. The most commonly utilized physiological parameters in biofeedback are muscle tension (electromyographic biofeedback) and temperature (thermal biofeedback). The effectiveness of hypnosis varies considerably among individuals. Hypnotic techniques teach patients to alter pain perception by having them focus on other sensations, localize the pain to another site, and dissociate themselves from a painful experience through imagery. Patients with chronic headaches and musculoskeletal disorders benefit most from these relaxation techniques.

Physical Therapy

Heat and cold can provide pain relief by alleviating muscle spasm. In addition, heat decreases joint stiffness and increases blood flow, and cold vasoconstricts and can reduce tissue edema. The analgesic action of heat and cold may at least partially be explained by the gate theory of pain processing.

Superficial heating modalities include conductive (hot packs, paraffin baths, fluidotherapy), convective (hydrotherapy), and radiant (infrared) techniques. Techniques for application of deep heat include ultrasound as well as shortwave and microwave diathermy. These modalities are more effective for pain involving deep joints and muscles. Cold is most effective for pain associated with acute injuries and edema. When applied selectively, cold can also relieve muscle spasm. Application may take the form of cold packs, ice massage, or vapocoolant sprays (ethyl chloride or fluoromethane).

Exercise should be part of any rehabilitation program for chronic pain. A graded exercise program prevents joint stiffness, muscle atrophy, and contractures, all of which can contribute to the patient’s pain and functional disabilities. McKenzie exercises are particularly helpful for patients with lumbar disc displacement. Patients may state that physical therapy has not helped in the past. The efficacy of previous physical therapy techniques should be assessed, and the appropriateness of current physical therapy sessions and of the home exercise program should also be evaluated. By facilitating increased range of motion and providing constant resistance, aquatherapy may be particularly helpful for patients who may not be able to tolerate other forms of therapy.

Acupuncture