Ulugol Ahmet, Karadag Hakan C, Ipci Yesim, Tamer Melek, Dokmeci Ismet
Department of Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey.
Neurosci Lett. 2004 Nov 23;371(2-3):167-70. doi: 10.1016/j.neulet.2004.08.061.
The antinociceptive action of cannabinoids in acute and inflammatory pain states have been well-documented. There is also accumulating evidence suggesting that cannabinoids are effective analgesics in chronic pain conditions. WIN 55,212-2, a mixed CB1 and CB2 cannabinoid receptor agonist, has been shown to be effective against hyperalgesia and allodynia in painful peripheral mononeuropathy. Recently, in addition to their spinal and supraspinal antinociceptive action, cannabinoids have also reported to exert local analgesic effects. The aim of this study is to observe the effect of a high affinity cannabinoid, WIN 55,212-2, on tactile allodynia and thermal hyperalgesia in diabetic rats. Diabetes was produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and this procedure resulted in neuropathic pain behaviors in the hindlimbs. Mechanical allodynia was detected by application of von Frey filaments to the plantar surface of the foot, and thermal hyperalgesia was studied using the Hargreaves' method; however, thermal hyperalgesia did not develop in diabetic rats. With its higher doses, both systemic (3 and 10 mg/kg, i.p.) and peripheral (30 microg, i.p.l.) injections of WIN 55,212-2 reduced mechanical allodynia. These results suggest that WIN 55,212-2 has an antiallodynic effect in streptozocin-induced diabetic rats and may be a promising approach in the treatment of diabetic neuropathy.
大麻素在急性和炎性疼痛状态下的抗伤害感受作用已有充分记录。也有越来越多的证据表明,大麻素在慢性疼痛状况下是有效的镇痛药。WIN 55,212-2,一种CB1和CB2大麻素受体混合激动剂,已被证明对疼痛性外周单神经病变中的痛觉过敏和异常性疼痛有效。最近,除了其脊髓和脊髓上的抗伤害感受作用外,大麻素还被报道具有局部镇痛作用。本研究的目的是观察高亲和力大麻素WIN 55,212-2对糖尿病大鼠触觉异常性疼痛和热痛觉过敏的影响。通过注射单剂量链脲佐菌素(50 mg/kg,腹腔注射)诱导糖尿病,该操作导致后肢出现神经病理性疼痛行为。通过将von Frey细丝应用于足底表面检测机械性异常性疼痛,并使用哈格里夫斯方法研究热痛觉过敏;然而,糖尿病大鼠未出现热痛觉过敏。使用较高剂量时,WIN 55,212-2的全身注射(3和10 mg/kg,腹腔注射)和外周注射(30μg,局部腹腔注射)均能减轻机械性异常性疼痛。这些结果表明,WIN 55,212-2对链脲佐菌素诱导的糖尿病大鼠具有抗异常性疼痛作用,可能是治疗糖尿病性神经病变的一种有前景的方法。