Abbreviations
AAG: α1-acid glycoprotein
AC: adenylyl cyclase
ACE: angiotensin-converting enzyme
ACh: acetylcholine
ACTH: corticotropin; formerly adrenocorticotropic hormone
ADH: antidiuretic hormone
ADME: absorption, distribution, metabolism, excretion
AT1: angiotensin II receptor, type 1
ATC: around the clock
BBB: blood-brain barrier
CaMK: Ca2+/calmodulin-dependent protein kinase
CDC: Centers for Disease Control and Prevention
CLIP: corticotropin-like intermediate lobe peptide
CNS: central nervous system
COPD: chronic obstructive pulmonary disease
COX: cyclooxygenase
CRH: corticotropin-releasing hormone
CSF: cerebrospinal fluid
CYP: cytochrome P450
DA: dopamine
DAMGO: [D-Ala2,MePhe4,Gly(ol)5]enkephalin
DHEA: dehydroepiandrosterone
DOR: δ opioid receptor
DYN: dynorphin
EEG: electroencephalogram
β-END: β-endorphin
L-ENK: Leu-enkephalin
ER/LA: extended-release/long-acting (a)
FDA: Food and Drug Administration
FSH: follicle-stimulating hormone
GABA: γ-aminobutyric acid
GI: gastrointestinal
GIRK: G protein–activated inwardly rectifying K+ channel
GnRH: gonadotropin-releasing hormone
GPCR: G protein-coupled receptor
GRK: GPCR kinase
HPA: hypothalamic-pituitary-adrenal
5HT: serotonin
IM: intramuscular
IP3: inositol triphosphate
IV: intravenous
JNK: c-Jun N-terminal kinase
KOR: κ opioid receptor
LH: luteinizing hormone
LPH: lipotropin
6-MAM: 6-monoacetylmorphine
MAO: monoamine oxidase
MAP: mitogen-activated protein
M-ENK: Met-enkephalin
MME: morphine milligram equivalent
MOR: μ opioid receptor
MSH: melanocyte-stimulating hormone
NAc: nucleus accumbens
NE: norepinephrine
α-NEO: α neoendorphin
NF-κB: nuclear factor kappa B
NMDA: N-methyl-D-aspartate
NOP: nociceptin/orphanin FQ (N/OFQ) receptor
NSAID: nonsteroidal anti-inflammatory drug
PAG: periaqueductal gray
PCA: patient-controlled anesthesia
PDMP: prescription drug monitoring program
PFC: prefrontal cortex
PI3K: phosphoinositide 3 kinase
PK: protein kinase
PLC: phospholipase C
POMC: pro-opiomelanocortin
pre-proDYN: pre-prodynorphin
pre-ProENK: pre-proenkephalin
SNRI: serotonin-norepinephrine reuptake inhibitor
SSRI: selective serotonin reuptake inhibitor
TM: transmembrane
VP: ventral pallidum
VTA: ventral tegmental area
Pain is a component of virtually all clinical pathologies, and management of pain is a primary clinical imperative. Opioids are a mainstay of acute pain treatment, but in recent years, the efficacy and safety of long-term use of opioids to treat chronic pain has been questioned as instances of addiction and death from their misuse have mounted. Opioids are certainly no longer first-line treatment of chronic pain, and a more conservative approach may involve other drug classes, such as NSAIDs, anticonvulsants, and antidepressants.
The term opiate refers to compounds structurally related to products found in opium, a word derived from opos, the Greek word for “juice,” natural opiates being derived from the resin of the opium poppy, Papaver somniferum. Opiates include the natural plant alkaloids, such as morphine, codeine, thebaine, and many semisynthetic derivatives. An opioid is any agent that has the functional and pharmacological properties of an opiate. Endogenous opioids are naturally occurring ligands for opioid receptors found in animals. The term endorphin not only is used synonymously with endogenous opioid peptides but also refers to a specific endogenous opioid, β-endorphin. The term narcotic was derived from the Greek word narkotikos, for “benumbing” or “stupor.” Although the term narcotic originally referred to any drug that induced narcosis or sleep, ...