Anandamide has been characterized as both an
endocannabinoid and endovanilloid. Consistent with its actions as an endovanilloid, previous studies have demonstrated that
anandamide can excite primary sensory neurons in vitro via transient receptor potential vanilloid type one (TRPV1) receptors. In the present study, we sought to determine if
anandamide excited cutaneous C nociceptors in vivo and if this excitation correlated with nocifensive behaviors. Using teased-fiber electrophysiological methods in the rat, C nociceptors isolated from the tibial nerve with receptive fields (RFs) on the plantar surface of the hindpaw were studied. Injection of
anandamide into the RF dose-dependently excited nociceptors at doses of 10 and 100 microg. The
TRPV1 receptor antagonists,
capsazepine or
SB 366791, were applied to the RF to determine if excitation by
anandamide was mediated through TRPV1 receptors. Intraplantar injection of either
capsazepine (10 microg) or
SB 366791 (3 microg) attenuated the excitation produced by 100 microg
anandamide. We also determined whether excitation of C nociceptors by
anandamide was associated with nocifensive behaviors. Intraplantar injection of 100 microg
anandamide produced nocifensive behaviors that were attenuated by pre-treatment with either
capsazepine or
SB 366791. Furthermore, we determined if intraplantar injection of
anandamide altered withdrawal responses to radiant heat. Neither intraplantar injection of
anandamide nor vehicle produced antinociception or
hyperalgesia to radiant heat. Our results indicate that
anandamide excited cutaneous C nociceptors and produced nocifensive behaviors via activation of TRPV1 receptors.