++
Headaches are estimated to affect over 90% of the general
population at some time in their lives1 and may
be encountered by physicians in a wide variety of clinical settings.
The overwhelming majority of recurrent headaches occur in the context
of what are known as primary headache disorders, in which no identifiable
underlying cause can be found. Some headaches, however, classified
as secondary headache disorders, are symptomatic of an underlying
abnormality that may include anything from transient viral illness,
to intracranial tumor, aneurysm, or drug withdrawal (for differential
diagnosis of secondary headache disorder, see Cutrer2).
Prevalence studies indicate that a benign process, such as a mild
febrile illness or alcohol withdrawal, usually causes secondary
headaches and that the lifetime prevalence of headache resulting
from more ominous intracranial structural lesions is less than 2%.3
++
Head pain occurs when nociceptive neurons within the trigeminal,
vagus, or glossopharyngeal cranial nerves or within the upper cervical
roots become depolarized. Information from procedures involving
intracerebral electrode implantation suggests that direct electrical
or mechanical activation of areas within the brain involved in pain
processing may also cause head pain.4 The causes
of head pain vary widely and include not only direct mechanical,
chemical, or inflammatory stimulation of pain-generating structures
but also less well-characterized events that occur in primary headache
disorders. Once initiated, the transmission and processing of the
painful information is likely to be quite similar regardless of
the inciting cause. In this chapter, we first review the anatomy
involved in generating generic head pain and then discuss current
theories of the pathophysiology of the major primary headache disorders,
including migraine, cluster headache, and tension-type headache.
++
Under normal physiologic conditions, the brain is largely insensate.
This has been demonstrated in neurosurgical procedures in which
stimulation of the brain parenchyma in awake patients caused no
pain.5,6 Head pain is mediated by projections from
the trigeminal and upper cervical dorsal root ganglia, which innervate
the pial, dural, and extracranial blood vessels. In general, these
pseudounipolar neurons innervate the vessels on the same side, which
can explain the unilateral distribution of pain in certain headache
types, but some of the cells project bilaterally to innervate midline
vessels. On activation, these unmyelinated C fibers transmit nociceptive
information from perivascular terminals through the trigeminal ganglia7 to
project centrally to synapses on second-order neurons within the
trigeminal nucleus caudalis. The primary neurotransmitter for the
C fibers is glutamate, but the primary afferents also co-store substance
P, calcitonin gene–related peptide and neurokinin A, as
well as other neurotransmitters and neuromodulators, in their central
and peripheral (e.g., meningeal) axons.
++
Activity in the trigeminal nucleus caudalis can be modulated
by projections from rostral trigeminal nuclei,8 the
periaqueductal gray matter, and the nucleus raphe magnus,9 as
well as by descending cortical inhibitory systems.9,10 From
the trigeminal nucleus caudalis, second-order neurons transmit the
nociceptive information, projecting to numerous subcortical ...