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The trigeminal sensory innervation of the major cerebral vessels is thought to carry the nociceptive information during a migraine headache, and this pain is usually referred to the forehead area. Using retrograde tracing techniques, we have described the distribution of sensory trigeminal cells that innervate the middle cerebral artery (MCA) and the forehead. Nearest-neighbor analysis of the ophthalmic division of the trigeminal ganglion revealed that cells innervating the forehead tend to be clumped around individual cells that innervate the MCA. An average of less than 1 cell per animal was found to project divergent collaterals to both areas. The close association of ganglion cell bodies innervating the cerebral vasculature and those innervating forehead areas may underlie the convergence of their central processes onto common brain-stem trigeminal nucleus cells, and thus the referral of headache pain. In contrast to the lack of ganglion cells with axonal collaterals to the cerebral vasculature and forehead, a significant population of cells that innervate the MCA also have collateral projections to other cerebral arterial branches (branches of the middle meningeal artery), as well as the surrounding dura. Thus, the innervation targets of individual trigeminal cells are very widespread intracranially (including arteries and dura), but separate cells in the ophthalmic division innervate extracranial targets.

Pattern of intracranial and extracranial projections of trigeminal ganglion cells