Influence of capsaicin cream in rats with peripheral neuropathy

We investigated the effect of topical application of capsaicin cream on wit hdrawal latency in the hind foot of rat in response to radiant heat in an e xperimental model of neuropathic pain. A neuropathic state was induced by l oose ligation of the sciatic nerve with chromic gut suture. A marked therma l hyperalgesia was observed in response to heat stimulus applied to the ope rated side from 3 days through 2 weeks, followed by a gradual return to the control level by 35 days after surgery. Capsaicin cream applied to both th e bilateral hind instep and sole once a day for a continuous period of 2 we eks or 4 weeks alleviated thermal hyperalgesia in a dose-dependent manner A remarkable effect was observed 2 weeks after the start of the application and this effect proved to be reversible. On the other hand, in sham-operate d animals when capsaicin cream was applied once daily from day 7 after the sham operation, from 1 day through 3 weeks following capsaicin application, withdrawal latency of the sham-operated paws of the capsaicin-treated grou p was significantly increased as compared to that of the vehicle cream-trea ted group. The effects of antagonists of glutamate receptor and tachykinin receptors were investigated 7 days post surgery. Pretreatment with MK-801 ( 0.5 mg kg(-1), i.p.), but not with CNQX (0.5 mg kg(-1), i.p.), reversed the thermal hyperalgesia following nerve injury. Neither of RP67580 (1-10 mg k g(-1), i.p.) nor SR48968 (1-10 mg kg(-1), i.p.) had any effect on the withd rawal latency in the injured and noninjured hind paw. These results suggest that although the manifestation of effectiveness may be delayed by changes in networks of neurotransmitters related to the nociceptive pathways follo wing nerve injury, longer-term repetitive application of capsaicin cream ha s a significant therapeutic effect on subjects with painful peripheral neur opathy. (C) 2001 Academic Press.