Novel expression of vanilloid receptor 1 on capsaicin-insensitive fibers accounts for the analgesic effect of capsaicin creamin neuropathic pain

摘要

Here,we investiated the mechanism of the antihyperalgesic effect of capsaicin cream in the nerve injury-induced neuropathic pain model in mice.In naive mice,application of capsaicin cream onto footpad caused no significant changes in the thermal latency in contrast to the severe thermal hyperalgesia induced by a capsaicin ointment.on the other hand,application of the cream 3 h before test concentration dependently reversed both thermal and mechanical hyperalgesia observed after partialsciatic nerve injury in mice.In algogenic-induced nociceptive flexion (ANF) test,application of 0.1% capsaicin creaminnaive mice blockd intraplantar 9i.pl.) nociceptin-and ATP-induced responses were unaffected.After nerve injury PGI_2 agonsit-induced flexion responses were hypersensitized,and capsaicin cream concentration dependently blocked these hyperalgesic responses.Intraplantar injection of capsaicin solution in ANF test also produced protent flexion responses in anive mice that were lost after neonatal capsaicin-induced flexion rsponses,suggesting novel expression of capsaicin receptors due to injury.The PGI-2 agonist-induced responses were also hypersensitized in such injured mice.Capsaicin receptors due to injury.The PGI_2 agonist-induced resposnes were also hypersensitizedinsuch injured mice.Capsaicin cream completely reversed both i.pl.capsaicin-or i.pl.PGI-2 agonist-induced hyperalgesia in neonatal capsaicin-treated in-jured mice.Finally,novel expression of VR1 receptors on neonatal capsaicin-insensitive neurons after nerve injury was confirmed by immunohistochemistry.The newly expressed VR1 recepther,our results suggest that novel expression of capsaicin receptors in neuropathic condition contributes to the analgesic effects of the capsaicin cream.