Preclinical research for the development of new treatment strategy to improve the outcomes of neuropathic pain management

据报道，只有不到50%的神经性疼痛患者用药物治疗满意。药物对神经性疼痛的低疗效可能是由于处方药物而不考虑疼痛的来源。采用胫骨神经瘤转位（TNT）模型，比较口服吗啡、普瑞巴林、加巴喷丁和度洛西汀治疗机械性异位痛和神经瘤痛的疗效。在TNT模型中，胫骨神经被截断，胫骨神经残端被转置到后肢外侧。TNT损伤后出现机械性异常痛和神经瘤痛。口服吗啡、普瑞巴林、加巴喷丁和度洛西汀，观察其抗异动和抗神经瘤疼痛的效果。吗啡、普瑞巴林、加巴喷丁和度洛西汀以剂量依赖的方式减弱机械异常性痛的水平。吗啡能减轻神经瘤疼痛，而普瑞巴林、加巴喷丁和度洛西汀则不能。吗啡对神经瘤痛的治疗效果低于机械性异常痛。在吗啡+普瑞巴林、吗啡+度洛西汀和普瑞巴林+度洛西汀两种药物联合研究中，所有药物联合对机械性异常性痛均产生协同作用，但对神经瘤痛无协同作用。这一数据表明吗啡的效价和疗效

It has been reported that less than 50% neuropathic pain patients satisfactorily treated with drugs. It is possible that this low efficacy of drugs on neuropathic pain might be due to the prescription of drugs regardless of the origin of pain. We compared the efficacy of orally administered morphine, pregabalin, gabapentin and duloxetine on mechanical allodynia with that on neuroma pain using the tibial neuroma transposition(TNT) model. In the TNT model, the tibial nerve is transected and the tibial nerve stump is transpositioned to the lateral aspect of the hindlimb. After TNT injury, mechanical allodynia and neuroma pain are observed. Morphine, pregabalin, gabapentin and duloxetine were administered orally and were examined the anti-allodynic and anti-neuroma pain effects. Morphine, pregabalin, gabapentin and duloxetine attenuated the level of mechanical allodynia in a dose-dependent manner. Morphine, but not pregabalin, gabapentin and duloxetine, attenuated the neuroma pain. Morphine was less potent in neuroma pain than in mechanical allodynia. In the two drugs combination studies(morphine+pregabalin, morphine+duloxetine and pregabalin+duloxetine), all drug combinations produced a synergistic effect on mechanical allodynia, but not on neuroma pain. This data indicated that the potency of morphine and the efficacy of