Neurotoxic action of capsaicin on spinal substance P neurons

The effects of capsaicin injections into neonatal rats on the ultrastructure of the neonatal dorsal horn and on some biochemical and behavioral parameters in the adult were examined. Electron microscopic observations revealed degeneration and glial engulfment of boutons and umyelinated axons in the dorsal horn 2 and 6 h after neonatal subcutaneous capsaicin injections. Capsaicin treatment had no effect on the activities of glutamic acid decarboxylase and choline acetyltransferase in the dorsal horn. Results of substance P measurements in the CNS showed no effect of capsaicin administration on striatal, hypothalamic or nigral substance P content, whereas substance P levels in the dorsal horn of the spinal cord were reduced by half. The density of [3H]naloxone binding sites in the dorsal horn was significantly reduced, while the affinity was not affected. Capsaicin-treated animals showed significantly increased latencies to respond to a noxious thermal stimulus in both tail-flick and hot-plate tests. The results are discussed in relation to the current concepts of the involvement of substance P and opiate systems in nociception and the potential use of neonatal capsaicin as a selective neurotoxin for the elucidation of the spinal mechanisms of pain.