Substance P and the sensory innervation of intracranial and extracranial feline cephalic arteries. Implications for vascular pain mechanisms in man.

Substance P, a putative neurotransmitter peptide present in a subpopulation of small sensory neurons, was measured in the walls of feline cranial arteries and systemic veins and arteries using a sensitive and specific radioimmunoassay. Substance P immunoreactivity exhibited a retention time identical to that of synthetic substance P when vessel extracts were subjected to reverse phase high performance liquid chromatography. Levels in cephalic arteries (453-1083 fmol/mg protein) were at least twice as high as amounts in systemic arteries and veins, and were significantly higher than those measured in the cornea and lip. Unilateral excision of the trigeminal ganglion decreased the peptide by 44 to 86 per cent in ipsilateral intracranial and extracranial arteries (e.g. external and internal maxillary, lingual, temporal, anterior, middle and posterior cerebral, superior cerebellar and posterior communicating arteries). Extracranial arteries were decreased on average by 78 per cent, whereas intracranial arteries were reduced by 55 per cent. Unilateral removal of the superior cervical sympathetic ganglion was without effect. The described pattern of sensory innervation provides a possible explanation for the referral of pain to the forehead and anterior scalp during attacks of migraine, and with arteritis and thrombosis involving vascular structures within the posterior fossa, the circle of Willis and the external carotid system of man.