Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia

Trends Pharmacol Sci. 2009 Feb;30(2):79-84. doi: 10.1016/ Epub 2008 Dec 11.


Despite the wealth of information on cannabinoid-induced peripheral antihyperalgesic and antinociceptive effects in many pain models, the molecular mechanism(s) for these actions remains unknown. Although metabotropic cannabinoid receptors have important roles in many pharmacological actions of cannabinoids, recent studies have led to the recognition of a family of at least five ionotropic cannabinoid receptors (ICRs). The known ICRs are members of the family of transient receptor potential (TRP) channels and include TRPV1, TRPV2, TRPV4, TRPM8 and TRPA1. Cannabinoid activation of ICRs can result in desensitization of the TRPA1 and TRPV1 channel activities, inhibition of nociceptors and antihyperalgesia and antinociception in certain pain models. Thus, cannabinoids activate both metabotropic and ionotropic mechanisms to produce peripheral analgesic effects. Here, we provide an overview of the pharmacology of TRP channels as ICRs.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cannabinoids / pharmacology*
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology*
  • Nociceptors / physiology
  • Pain / metabolism
  • Pain / physiopathology*
  • Pain Threshold
  • Receptors, Cannabinoid / physiology*
  • Sensory Receptor Cells / physiology
  • Transient Receptor Potential Channels / physiology*


  • Cannabinoids
  • Receptors, Cannabinoid
  • Transient Receptor Potential Channels