LOCALIZATION AND ACTIVATION OF SUBSTANCE-P RECEPTORS IN UNMYELINATED AXONS OF RAT GLABROUS SKIN

Immunohistochemical staining for the substance P (neurokinin 1, NK1) r eceptor labels 32% of the unmyelinated axons in the glabrous skin of t he rat hindpaw. This is the first demonstration of substance P (SP) re ceptors associated with the membranes of primary afferent fibers. Inje ction of SP into the subcutaneous tissue of the third hind toe results in behavioral changes interpreted as mechanical hyperalgesia and mech anical allodynia. These nocifensive behaviors can be blocked by the NK 1 antagonist CP99,994-1. The presence of peripheral axons immunolabell ed for NK1 receptors and the demonstration that exogenous peripheral S P causes nocifensive behaviors would seem to indicate that SP can have a direct effect on sensory afferents with activation of these recepto rs resulting in fine afferent firing and thus the pain-related behavio rs. Additionally, the presence of round, clear vesicles in some of the SP receptor-labelled axons suggests the presence of autoreceptors sin ce it is known that many primary sensory afferents contain SP.