Changes in fibre populations of the rat hairy skin following selective chemodenervation by capsaicin

Perineural application of capsaicin results in a selective and permanent re duction in the sensitivity to noxious chemical and heat stimuli and elimina tion of the neurogenic inflammatory response. The present quantitative immu nohistochemical study has been undertaken to reveal the populations of cuta neous afferent nerves that are affected by perineural capsaicin treatment. Areas of intact and chemodenervated skin were determined with the aid of th e vascular labelling technique. In sections taken from intact skin areas, s taining with antibodies against protein gene product 9.5 revealed a rich ep idermal innervation. Fibres immunoreactive for growth-associated protein 43 were also abundant; nerve fibres immunoreactive for substance P and calcit onin gene-related peptide were less numerous. Somatostatin- and RT97-immuno reactive fibres were seen only in the subepidermal layer. In sections taken from skin areas supplied by the sciatic nerve treated with capsaicin 3 day s previously, the number of epidermal nerve fibres immunoreactive to protei n gene product 9.5, growth-associated protein 43, substance P and calcitoni n gene-related peptide was reduced by 90%, 95%, 97% and 66%, respectively. These changes persisted for at least 42 days. The findings reveal that the majority of epidermal axons are capsaicin-sensitive and comprise a chemical ly heterogeneous population. Reductions in cutaneous fibre populations foll owing perineural capsaicin treatment may result from both the degeneration of sensory axons and the depletion of neuron-specific macromolecules. In ad dition, most cutaneous nociceptive axons may not use the major sensory neur opeptides substance P and calcitonin gene-related peptide as afferent neuro transmitters.