Funded by Deanship of Scientific Research
Amount: 10000 JD
NE 19550 (olvanil) is a non-pungent synthetic analogue of capsaicin, the natural pungent ingredient of capsicum which activates the transient receptor potential of vanilloid type-1 (TRPV1) channel and was developed as a potential analgesic compound. Olvanil has potent anti-hyperalgesic effects in several experimental models of chronic pain. Here we report the inhibitory effects of olvanil on nociceptive processing using cultured dorsal root ganglion (DRG) neurons and compare the effects of capsaicin and olvanil on thermal nociceptive processing in vivo, potential contributions of the cannabinoid CB1 receptor is also investigated.
Both olvanil (100 nM) and capsaicin (100 nM) produced a significant increase in intracellular calcium concentrations [Ca2+]i in cultured DRG neurons. Olvanil was able to desensitise TRPV1 responses to further capsaicin exposure more effectively than capsaicin. Intraplantar injection of capsaicin (0.1, 0.3 and 1 µg) produced a robust TRPV1-dependant thermal hyperalgesia in rats, in a manner, whilst olvanil (0.1, 0.3 and 1 µg) did not produce hyperalgesia, emphasizing its lack of pungency. The highest dose of olvanil significantly reduced the hyperalgesic effects of capsaicin in vivo. Intraplantar injection of the selective cannabinoid CB1 receptor antagonist rimonabant (1 µg) did not alter capsaicin-induced thermal hyperalgesia nor on the desensitizing properties of olvanil, suggesting a lack of involvement of CB1 receptors.