Bridges D, Ahmad K, Rice A S
Pain Research, Imperial College School of Medicine, Chelsea and Westminster Hospital Campus, London, SW10 9NH.
Br J Pharmacol. 2001 Jun;133(4):586-94. doi: 10.1038/sj.bjp.0704110.
The analgesic properties of the synthetic cannabinoid WIN55,212-2 were investigated in a model of neuropathic pain. In male Wistar rats, bilateral hind limb withdrawal thresholds to cold, mechanical and noxious thermal stimuli were measured. Following this, unilateral L5 spinal nerve ligation was performed. Seven days later, sensory thresholds were reassessed and the development of allodynia to cold and mechanical stimuli and hyperalgesia to a noxious thermal stimulus confirmed. The effect of WIN55,212-2 (0.1 - 5.0 mg kg(-1), i.p.) on the signs of neuropathy was then determined; there was a dose related reversal of all three signs of painful neuropathy at doses which did not generally alter sensory thresholds in the contralateral unligated limb. This effect was prevented by co-administration of the CB(1) receptor antagonist SR141716a, but not by co-administration of the CB(2) receptor antagonist SR144528, suggesting this action of WIN55,212-2 is mediated via the CB(1) receptor. Administration of SR141716a alone had no affect on the observed allodynia and hyperalgesia, which does not support the concept of an endogenous analgesic tone. These data indicate that cannabinoids may have therapeutic potential in neuropathic pain, and that this effect is mediated through the CB(1) receptor.
在神经性疼痛模型中研究了合成大麻素WIN55,212-2的镇痛特性。在雄性Wistar大鼠中，测量双侧后肢对冷、机械和有害热刺激的退缩阈值。在此之后，进行单侧L5脊神经结扎。7天后，重新评估感觉阈值，并确认对冷和机械刺激的异常性疼痛以及对有害热刺激的痛觉过敏的发展。然后确定WIN55,212-2（0.1 - 5.0 mg kg(-1)，腹腔注射）对神经病变体征的影响；在通常不会改变对侧未结扎肢体感觉阈值的剂量下，疼痛性神经病变的所有三种体征都出现了剂量相关的逆转。这种作用被CB(1)受体拮抗剂SR141716a的共同给药所阻断，但未被CB(2)受体拮抗剂SR144528的共同给药所阻断，这表明WIN55,212-2的这种作用是通过CB(1)受体介导的。单独给予SR141716a对观察到的异常性疼痛和痛觉过敏没有影响，这不支持内源性镇痛张力的概念。这些数据表明大麻素在神经性疼痛中可能具有治疗潜力，并且这种作用是通过CB(1)受体介导的。
