The abnormal cannabidiol analogue O-1602 reduces nociception in a rat model of acute arthritis via the putative cannabinoid receptor GPR55.

Abstract

Cannabinoids classically act via CB₁ and CB₂ receptors to modulate nociception; however, recent findings suggest that some cannabinoids bind to atypical receptors. One such receptor is GPR55 which is activated by the abnormal cannabidiol analogue O-1602. This study investigated whether the synthetic GPR55 agonist O-1602 can alter joint nociception in a rat model of acute joint inflammation. Acute (24 h) inflammatory joint pain was induced in male Wistar rats by intra-articular injection of 2% kaolin and 2% carrageenan. Single unit extracellular recordings were made from arthritic joint afferents in response to mechanical rotation of the knee. Peripheral administration of O-1602 significantly reduced movement-evoked firing of nociceptive C fibres and this effect was blocked by the GPR55 receptor antagonist O-1918. Co-administration of the CB₁ and CB₂ antagonists (AM281 and AM630 respectively) had no effect on O-1602 responses. This study clearly shows that atypical cannabinoid receptors are involved in joint nociception and these novel targets may be advantageous for the treatment of inflammatory pain.

• Authors: Niklas Schuelert, Jason J McDougall
• Journal: Neuroscience letters (Neurosci Lett) Vol. 500 Issue 1 Pg. 72-6 (Aug 01 2011) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 21683763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• Receptors, G-Protein-Coupled
• Cannabidiol
• Kaolin
• O-1602 compound
• Carrageenan

Topics

• Action Potentials
• Acute Disease
• Afferent Pathways
• Animals
• Arthritis (chemically induced, drug therapy, physiopathology)
• Cannabidiol (analogs & derivatives, pharmacology)
• Carrageenan
• Hindlimb
• Joints (drug effects, physiopathology)
• Kaolin
• Male
• Movement
• Nerve Fibers, Unmyelinated (drug effects, physiology)
• Nociception (drug effects)
• Rats
• Rats, Wistar
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors)
• Receptor, Cannabinoid, CB2 (antagonists & inhibitors)
• Receptors, G-Protein-Coupled (agonists, antagonists & inhibitors, physiology)