The pain of a migraine attack is often described as unilateral, with a throbbing or pulsating quality. The
middle meningeal artery (MMA) is the largest artery supplying the dura mater, is paired, and pain-producing in humans. This artery, or its branches, and other large intracranial extracerebral vessels have
been implicated in the pathophysiology of migraine by theories suggesting neurogenic inflammation or
cranial vasodilatation, or both, as explanations for the pain of migraine. Having previously studied in detail
the distribution of the second order neurons that are involved in the transmission of nociceptive signals from
intracranial venous sinuses, we sought to compare the distribution of second order neurons from a pain-producing intracranial artery in both monkey and cat. By electrically stimulating the middle meningeal
artery in these species and using immunohistochemical detection of the proto-oncogene Fos as a marker of
neuronal activation, we have mapped the sites of the central trigeminal neurons which may be involved in
transmission of nociception from intracranial extracerebral arteries. Ten cats and 3 monkeys were
anaesthetised with α-chloralose and the middle meningeal artery was isolated following a temporal
craniotomy. The animals were maintained under stable anaesthesia for 24 h to allow Fos expression due to
the initial surgery to dissipate. Following the rest period, the vessel was carefully lifted onto hook electrodes,
and then left alone in control animals (cat n = 3), or stimulated (cat n = 6, monkey n = 3). Stimulation of
the left middle meningeal artery evoked Fos expression in the trigeminocervical nucleus, consisting of the
dorsal horn of the caudal medulla and upper 2 divisions of the cervical spinal cord, on both the ipsilateral
and contralateral sides. Cats had larger amounts of Fos expressed on the ipsilateral than on the
contralateral side. Fos expression in the caudal nucleus tractus solitarius and its caudal extension in lamina
X of the spinal cord was seen bilaterally in response to middle meningeal artery stimulation. This study
demonstrates a comparable anatomical distribution of Fos activation between cat and monkey and, when
compared with previous studies, between this arterial structure and the superior sagittal sinus. These data
add to the overall picture of the trigeminovascular innervation of the intracranial pain-producing vessels
showing marked anatomical overlap which is consistent with the often poorly localised pain of migraine.