Department of Physiology & Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N4N1, Canada.
Neurosci Lett. 2011 Aug 1;500(1):72-6. doi: 10.1016/j.neulet.2011.06.004. Epub 2011 Jun 13.
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.
大麻素经典地通过 CB₁ 和 CB₂ 受体来调节伤害感受；然而，最近的发现表明，一些大麻素结合到非典型受体上。这样的受体之一是 GPR55，它被异常的大麻二酚类似物 O-1602 激活。本研究调查了合成 GPR55 激动剂 O-1602 是否可以改变急性关节炎症大鼠模型中的关节疼痛。通过向膝关节内注射 2%的高岭土和 2%的角叉菜胶，在雄性 Wistar 大鼠中诱导急性（24 小时）炎症性关节疼痛。对关节炎传入神经进行机械旋转，以响应的方式进行单个单位的细胞外记录。外周给予 O-1602 可显著降低伤害性 C 纤维的运动诱发放电，并且这种作用被 GPR55 受体拮抗剂 O-1918 阻断。CB₁ 和 CB₂ 拮抗剂（分别为 AM281 和 AM630）的共同给药对 O-1602 的反应没有影响。本研究清楚地表明，非典型大麻素受体参与关节疼痛，这些新的靶点可能有利于治疗炎症性疼痛。
