Background: Olvanil (NE 19550) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient\nof capsicum which activates the transient receptor potential vanilloid type-1 (TRPV1) channel and was developed as\na potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of\nchronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root\nganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in\nvivo; potential contributions of the cannabinoid CB1 receptor to olvanilâ��s anti-hyperalgesic effects were also\ninvestigated.\nMethods: A hot plate analgesia meter was used to evaluate the anti-nociceptive effects of olvanil on capsaicin-induced\nthermal hyperalgesia and the role played by CB1 receptors in mediating these effects. Single cell calcium imaging studies\nof DRG neurons were employed to determine the desensitizing effects of olvanil on capsaicin-evoked calcium responses.\nStatistical analysis used Studentâ��s t test or one way ANOVA followed by Dunnettâ��s post-hoc test as appropriate.\nResults: Both olvanil (100 nM) and capsaicin (100 nM) produced significant increases in intracellular calcium\nconcentrations [Ca2+]i in cultured DRG neurons. Olvanil was able to desensitise TRPV1 responses to further capsaicin\nexposure more effectively than capsaicin. Intraplantar injection of capsaicin (0.1, 0.3 and 1 �¼g) produced a robust TRPV1-\ndependant thermal hyperalgesia in rats, whilst olvanil (0.1, 0.3 and 1 �¼g) produced no hyperalgesia, emphasizing its lack\nof pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar\ninjection of the selective cannabinoid CB1 receptor antagonist rimonabant (1 �¼g) altered neither capsaicin-induced\nthermal hyperalgesia nor the desensitizing properties of olvanil, indicating a lack of involvement of CB1 receptors.\nConclusions: Olvanil is effective in reducing capsaicin-induced thermal hyperalgesia, probably via directly desensitizing\nTRPV1 channels in a CB1 receptor-independent fashion. The results presented clearly support the potential for olvanil in\nthe development of new topical analgesic preparations for treating chronic pain conditions while avoiding the unwanted\nside effects of capsaicin treatments.
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