Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist

Clin Exp Dermatol. 2018 Jul;43(5):553-558. doi: 10.1111/ced.13398. Epub 2018 Feb 9.

Abstract

Background: Cannabinoids have been used for their analgesic and euphoric effects for millennia, but recently the antipruritic effects of cannabis have been discovered. Considering the similarities between pain and itch sensations, we hypothesized that cannabinoid receptors may play a role in the antipruritic effects of cannabinoids.

Aim: To analyse the role of the spinal cannabinoid receptors, CB1 and CB2, in the antipruritic effects of the cannabinoid agonist WIN 55,212-2.

Methods: Male Balb/c mice weighing 20-30 g were used. Scratching behaviour in the mice was produced by injection of serotonin 5 μg/50 μL intradermally into the nape of the neck. Scratching of the site of injection by the hind paws was video-recorded for 30 min. After testing different doses of WIN 55,212-2 [1, 3 and 10 mg/kg intraperitoneally (IP)], the effects of the CB1 receptor antagonist, AM-251 [1 μg/mouse administered intrathecally (IT)] and the CB2 receptor antagonist AM-630 (4 μg/mouse IT) on the antipruritic effects of WIN 55,212-2 were studied using a rotarod apparatus.

Results: WIN 55,212-2 (1, 3 or 10 mg/kg IP) dose-dependently decreased serotonin-induced scratches. The receptor antagonist CB1 partially reversed the effects of WIN 55,212-2 (P < 0.05); whereas CB2 had no statistically significant effect. WIN 55,212-2 impaired motor function only at the highest dose given (10 mg/kg, P < 0.05).

Conclusions: Our findings support prior researches indicating that cannabinoids exert antipruritic effects. Moreover, our results show that the antipruritic effects of cannabinoids are partially mediated by spinal CB1 receptors.

MeSH terms

  • Animals
  • Benzoxazines / administration & dosage
  • Benzoxazines / therapeutic use*
  • Cannabinoid Receptor Agonists / administration & dosage
  • Cannabinoid Receptor Agonists / therapeutic use*
  • Cannabinoid Receptor Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Morpholines / administration & dosage
  • Morpholines / therapeutic use*
  • Naphthalenes / administration & dosage
  • Naphthalenes / therapeutic use*
  • Piperidines / pharmacology
  • Pruritus / chemically induced
  • Pruritus / drug therapy*
  • Pyrazoles / pharmacology
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB2 / metabolism*
  • Serotonin
  • Spinal Cord / metabolism*

Substances

  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Cannabinoid Receptor Antagonists
  • Indoles
  • Morpholines
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Serotonin
  • AM 251
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • iodopravadoline