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Headache is among the most common reasons patients seek medical attention and is responsible, on a global basis, for more disability than any other neurologic problem. Diagnosis and management are based on a careful clinical approach augmented by an understanding of the anatomy, physiology, and pharmacology of the nervous system pathways mediating the various headache syndromes. This chapter will focus on the general approach to a patient with headache; migraine and other primary headache disorders are discussed in Chap. 430.


A classification system developed by the International Headache Society ( characterizes headache as primary or secondary (Table 16-1). Primary headaches are those in which headache and its associated features are the disorder itself, whereas secondary headaches are those caused by exogenous disorders (Headache Classification Committee of the International Headache Society, 2018). Primary headache often results in considerable disability and a decrease in the patient’s quality of life. Mild secondary headache, such as that seen in association with upper respiratory tract infections, is common but rarely worrisome. Life-threatening headache is relatively uncommon, but vigilance is required in order to recognize and appropriately treat such patients.

TABLE 16-1Common Causes of Headache


Pain usually occurs when peripheral nociceptors are stimulated in response to tissue injury, visceral distension, or other factors (Chap. 13). In such situations, pain perception is a normal physiologic response mediated by a healthy nervous system. Pain can also result when pain-producing pathways of the peripheral or central nervous system (CNS) are damaged or activated inappropriately. Headache may originate from either or both mechanisms. Relatively few cranial structures are pain producing; these include the scalp, meningeal arteries, dural sinuses, falx cerebri, and proximal segments of the large pial arteries. The ventricular ependyma, choroid plexus, pial veins, and much of the brain parenchyma are not pain producing.

The key structures involved in primary headache are the following:

  • The large intracranial vessels and dura mater, and the peripheral terminals of the trigeminal nerve that innervate these structures

  • The caudal portion of the trigeminal nucleus, which extends into the dorsal horns of the upper cervical spinal cord and receives input from the first and second cervical nerve roots (the trigeminocervical complex)

  • Rostral pain-processing regions, such as the ventroposteromedial thalamus and the cortex

  • The pain-modulatory systems in the brain that modulate input from the trigeminal nociceptors at all levels of the pain-processing pathways and ...

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