Delta 9-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism

J Neurosci. 2002 Jun 1;22(11):4720-7. doi: 10.1523/JNEUROSCI.22-11-04720.2002.

Abstract

Although Delta(9)-tetrahydrocannabinol (THC) produces analgesia, its effects on nociceptive primary afferents are unknown. These neurons participate not only in pain signaling but also in the local response to tissue injury. Here, we show that THC and cannabinol induce a CB(1)/CB(2) cannabinoid receptor-independent release of calcitonin gene-related peptide from capsaicin-sensitive perivascular sensory nerves. Other psychotropic cannabinoids cannot mimic this action. The vanilloid receptor antagonist ruthenium red abolishes the responses to THC and cannabinol. However, the effect of THC on sensory nerves is intact in vanilloid receptor subtype 1 gene knock-out mice. The THC response depends on extracellular calcium but does not involve known voltage-operated calcium channels, glutamate receptors, or protein kinases A and C. These results may indicate the presence of a novel cannabinoid receptor/ion channel in the pain pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects*
  • Afferent Pathways / physiology
  • Animals
  • Biological Assay
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcium / metabolism
  • Cannabinoids / pharmacology
  • Cannabinol / pharmacology*
  • Capsaicin / pharmacology
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology*
  • Female
  • Hepatic Artery / drug effects
  • Hepatic Artery / innervation
  • Hepatic Artery / physiology
  • In Vitro Techniques
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / innervation
  • Mesenteric Arteries / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology
  • Pain
  • Psychotropic Drugs / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB2*
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / deficiency
  • Receptors, Drug / drug effects*
  • Receptors, Drug / metabolism
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Cannabinoids
  • Cnr2 protein, rat
  • Psychotropic Drugs
  • Receptor, Cannabinoid, CB2
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Dronabinol
  • Cannabinol
  • Calcitonin Gene-Related Peptide
  • Capsaicin
  • Calcium