The time course and specificity of the changes in the behavioural and dorsal horn cell responses to noxious stimuli following peripheral nerve capsaicin treatment in the rat.

Capsaicin, a neurotoxin which acts specifically on sensory primary afferent C-fibres was applied locally to one sciatic nerve of a group of rats. One to sixteen days following this a series of behavioural and electrophysiological studies were performed. The latency of foot withdrawal of the rats to a controlled thermal noxious stimuli was significantly elevated (200%). The peak increase occurred on day 1 after treatment; the response then fell to a steady but elevated level for up to 16 days. Responses to noxious mechanical stimuli were unaffected by capsaicin treatment. Single unit analysis of the dorsal horn of the spinal cord showed that the number of neurones in deep laminae (4, 5 and 6) responding to a C peripheral volley was normal (60%) for the first 2 days after treatment. On day 3 post treatment, the number of cells with a C input began to fall reaching a maximal decrease on day 7 (25%), where it remained up to day 16. In contrast to this delayed effect on C-evoked responses, the number of cells responding to noxious heating of the skin fell from control levels of 60% down to 20% on day 1 and remained decreased for up to 16 days. The onset of thermal analgesia following local, capsaicin treatment, therefore, closely parallels the time course of the decrease of noxious heat-evoked responses in the dorsal horn. Since at early pretreatment times, the electrically C-evoked activity is normal these effects are likely to be due to action on peripheral C-fibre nociceptors in the skin. At a later stage capsaicin also appears to act on the central terminals of fibres reducing transmission to second order dorsal horn neurones.