Differences in peripheral endocannabinoid modulation of scratching behavior in facial vs. spinally-innervated skin

Jessica Marie Spradley, Auva Davoodi, Leland Bruce Gee, Mirela Iodi Carstens, Earl Carstens

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Cannabinoids suppress nocifensive behaviors in rodents. We presently investigated peripheral endocannabinoid modulation of itch- and pain-related behaviors elicited from facial vs. spinally-innervated skin of rats. Intradermal (id) injection of the pruritogen serotonin (5-HT) elicited significantly more hindlimb scratch bouts, and longer cumulative time scratching, when injected in the rostral back compared to the cheek. Pretreatment of skin with inhibitors of degrading enzymes for the endocannabinoids anandamide (URB597) or 2-arachidonoylglycerol (JZL184) significantly reduced scratching elicited by 5-HT in the rostral back. These effects were prevented by co-treatment with antagonists of the CB1 (AM251) or CB2 receptor (AM630), implicating both receptor subtypes in endocannabinoid suppression of scratching in spinally-innervated skin. Conversely, pretreatment with either enzyme inhibitor, or with AM630 alone, increased the number of scratch bouts elicited by id 5-HT injection in the cheek. Moreover, pretreatment with JZL184 also significantly increased pain-related forelimb wipes directed to the cheek following id injection of the algogen, allyl isothiocyanate (AITC; mustard oil). Thus, peripheral endocannabinoids have opposite effects on itch-related scratching behaviors in trigeminally- vs. spinally-innervated skin. These results suggest that increasing peripheral endocannabinoid levels represents a promising therapeutic approach to treat itch arising from the lower body, but caution that such treatment may not relieve, and may even exacerbate, itch and pain arising from trigeminally-innervated skin of the face or scalp.

Original languageEnglish (US)
Pages (from-to)743-749
Number of pages7
Issue number4
StatePublished - Sep 2012


  • C-fiber
  • Cannabinoid receptor
  • CB
  • CB
  • Endocannabinoid
  • G-protein-coupled receptor
  • Itch
  • Scratch
  • Serotonin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology


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