The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain.
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.
Bridges
D
D
Pain Research, Imperial College School of Medicine, Chelsea and Westminster Hospital Campus, London, SW10 9NH.
Ahmad
K
K
Rice
A S
AS
D000700:Analgesics / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D009025:Morpholines / Q000627:therapeutic use*; D009281:Naphthalenes / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant
D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant