Excitation of cutaneous C nociceptors by intraplantar administration of anandamide

Carl Potenzieri, Thaddeus S. Brink, Donald A. Simone

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21 Scopus citations


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 μg. 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 μg) or SB 366791 (3 μg) attenuated the excitation produced by 100 μg anandamide. We also determined whether excitation of C nociceptors by anandamide was associated with nocifensive behaviors. Intraplantar injection of 100 μg 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.

Original languageEnglish (US)
Pages (from-to)38-47
Number of pages10
JournalBrain Research
StatePublished - May 1 2009

Bibliographical note

Funding Information:
The authors thank Dr. Virginia S. Seybold for critically reading an early manuscript of this paper. This work was supported by grants from the National Institutes of Health (CA91007 and DA011471 to DAS). CP was supported by training grants from the National Institute on Drug Abuse (5T32-DA007234 and 1F31-DA024541). TB was supported by a training grant from the National Institute of Dental and Craniofacial Research (T32-DE007288).


  • Cannabinoid
  • Nocifensive behavior
  • Primary afferent electrophysiology
  • TRPV1 receptor


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