Substance P in the trigeminal system at postmortem: evidence for a role in pain pathways in man.

It is suspected that substance P has a role in primary afferent neurotransmission specifically concerned with nociception. This hypothesis has been developed from studies using experimental animals. In the present study indirect immunofluorescence has been used to examine the distribution of substance P-containing neurones in the human trigeminal system. The 5 specimens examined were obtained at autopsy. The antibody has been characterised by radio-immunoassay. In addition, neutralisation tests were performed. Approximately 15% of the neuronal perikarya observed in the trigeminal ganglia contained substance P-like material. The central nerve terminal distribution of these neurones was observed in the peripheral layers of nucleus caudalis and the caudal regions of the nucleus interpolaris. Peripheral distribution of fibres, presumably axon terminals, was observed in the dermis of the scalp subjacent to the epidermis. Rarely, fibres penetrated the lower layers of the epidermis. Nerve fibres were seen in the media and adventitia at the origin of the major cerebral vessels, the middle meningeal, muscular and scalp arteries. Nerve fibres were not observed elsewhere in muscle, in the leptomeninges or dura mater, except in and immediately adjacent to the venous sinuses. The distribution of substance P-containing neurones correlates closely with clinical studies which document the blood vessels and skin as the major pain sensitive structures of the scalp and cranium. This is evidence in man that substance P is involved in nociceptive pathways.