title: 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.affiliation: Department of Physiology & Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N4N1, Canada.
authors.forename: Niklas
authors.initials: N
authors.lastname: Schuelert
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
mesh_terms: D000200:Action Potentials; D000208:Acute Disease; D000344:Afferent Pathways; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002185:Cannabidiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002351:Carrageenan; D006614:Hindlimb; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D007616:Kaolin; D008297:Male; D009068:Movement; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D059225:Nociception / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043562:Receptors, G-Protein-Coupled; D002185:Cannabidiol; D007616:Kaolin; C568537:O-1602 compound; D002351:Carrageenan