Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Finland.
Eur J Pain. 2011 Aug;15(7):732-40. doi: 10.1016/j.ejpain.2010.12.001. Epub 2011 Jan 8.
Neuropathic pain is caused by damage or malfunctioning of the nervous system. It is fairly common and more resistant to treatment than other types of pain. Since nitecapone, an inhibitor of catechol-O-methyl-transferase (COMT), has decreased neuropathic symptoms in diabetic rats, we studied its effects in another model of neuropathic pain, the spinal nerve ligation (SNL) model. Spinal nerves L5-6 were ligated in male Wistar rats under anaesthesia to produce the SNL model of neuropathic pain. Nitecapone (30 mg/kg, i.p.) or vehicle was administered once daily starting either 1h before or 2 days after surgery and continued for 14-19 days. Threshold for mechanical allodynia was measured with the digital von Frey test and responses to cold stimuli with the acetone test, before surgery and every other day after it 1h before drug administration. Mechanical and cold allodynia developed in all study groups. Both nitecapone treatments significantly reduced mechanical allodynia and withdrawal thresholds were 80-95% higher compared with the control group. In the acetone test, both nitecapone groups also showed less signs of cold allodynia than the control groups. In nitecapone-naïve animals a single dose of nitecapone also reduced mechanical allodynia on the 14th day after the surgery. Nitecapone reduced the symptoms of neuropathic pain after the SNL, which is in line with the earlier study. Our results suggest that nitecapone and other COMT inhibitors should be studied further in the treatment of neuropathic pain.
神经病理性疼痛是由神经系统损伤或功能障碍引起的。它相当常见,比其他类型的疼痛更难治疗。由于儿茶酚-O-甲基转移酶 (COMT) 的抑制剂尼卡朋可降低糖尿病大鼠的神经病理性症状,我们研究了它在另一种神经病理性疼痛模型,即脊神经结扎 (SNL) 模型中的作用。雄性 Wistar 大鼠在麻醉下结扎 L5-6 脊神经,以产生神经病理性疼痛的 SNL 模型。尼卡朋(30mg/kg,ip)或载体在手术前 1 小时或手术后 2 天开始每天给药一次,持续 14-19 天。使用数字 von Frey 测试测量机械性痛觉过敏的阈值,使用丙酮测试测量对冷刺激的反应,在手术前和给药前 1 小时的每两天进行一次。所有研究组均出现机械性和冷性痛觉过敏。两种尼卡朋治疗均显著降低机械性痛觉过敏,与对照组相比,退缩阈值提高了 80-95%。在丙酮测试中,与对照组相比,尼卡朋治疗组也表现出较少的冷性痛觉过敏迹象。在尼卡朋-naïve 动物中,单次给予尼卡朋也可在手术后第 14 天降低机械性痛觉过敏。尼卡朋降低了 SNL 后的神经病理性疼痛症状,这与早期研究一致。我们的结果表明,尼卡朋和其他 COMT 抑制剂应进一步研究用于治疗神经病理性疼痛。