Immunohistochemical localization of 5-HT2A receptors in peripheral sensory axons in rat glabrous skin.

Serotonin (5-hydroxytryptamine, 5-HT) is a well known inflammatory mediator and algesic substance. It has been hypothesized that 5-HT can have a direct action on peripheral sensory axons, but there has been no anatomical demonstration of 5-HT receptors on peripheral primary afferent processes. The present study shows that 32% of unmyelinated axons at the dermal-epidermal junction are immunohistochemically stained with antibodies directed against the 5-HT2A receptor providing anatomical evidence that 5-HT can have a direct effect on sensory fibers in the skin. Furthermore, encapsulated nerve endings in Pacinian corpuscles also contain reaction product following immunostaining for 5-HT2A receptors, indicating that large myelinated axons can be activated by endogenous serotonin. These data suggest that peripherally acting 5-HT2A antagonists may be effective in reducing pain of peripheral origin.