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

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.

► The abnormal cannabidiol analogue O-1602 reduced noxious mechanosensitivity in acutely inflamed rat knee joints.
► This effects was restricted to nociceptive C-fibres but not A-δ fibres.
► O-1602-induced anti-nociception was not blocked by the classic CB1 receptor antagonist AM281 nor the classic CB2 receptor antagonist AM630.
► The GPR55 antagonist O-1918 was able to inhibit O-1602 effects.