Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids

Acta Neuropsychiatr. 2016 Dec;28(6):321-326. doi: 10.1017/neu.2016.16.

Abstract

Background: For centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common.

Objective: The goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2. Material and methods Scratching behaviour was induced by intradermal injection of serotonin (50 µg/50 µl/mouse) to Balb/c mice. The neurotoxins 5,7-dihydroxytryptamine (5,7-DHT, 50 μg/mouse) and 6-hydroxydopamine (6-OHDA, 20 μg/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. WIN 55,212-2 (1, 3, 10 mg/kg, i.p.) dose-dependently attenuated serotonin-induced scratches. Neurotoxic destruction of neither the serotonergic nor the noradrenergic systems by 5,7-DHT and 6-OHDA, respectively, had any effect on the antipruritic action of WIN 55,212-2.

Conclusion: Our findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.

Keywords: 212-2; WIN 55; cannabinoid system; descending inhibition; pruritus.

MeSH terms

  • 5,7-Dihydroxytryptamine / administration & dosage
  • Animals
  • Antipruritics / administration & dosage*
  • Benzoxazines / administration & dosage*
  • Cannabinoid Receptor Agonists / administration & dosage*
  • Dose-Response Relationship, Drug
  • Mice
  • Mice, Inbred BALB C
  • Morpholines / administration & dosage*
  • Naphthalenes / administration & dosage*
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Norepinephrine / physiology*
  • Oxidopamine / administration & dosage
  • Pruritus / chemically induced
  • Pruritus / physiopathology*
  • Serotonin / administration & dosage
  • Serotonin / physiology*
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology

Substances

  • Antipruritics
  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Morpholines
  • Naphthalenes
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Win 55212-2
  • Oxidopamine
  • Norepinephrine