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

据报道，不到50%的神经病理性疼痛患者通过药物治疗获得满意的疗效。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起源。我们使用胫骨神经瘤转位（TNT）模型比较了口服吗啡、普瑞巴林、加巴喷丁和度洛沙酮对机械性异常性疼痛和神经瘤疼痛的疗效。在TNT模型中，将胫神经横断，并将胫神经残端移位至后肢的外侧。TNT损伤后，观察到机械性异常性疼痛和神经瘤疼痛。口服吗啡、普瑞巴林、加巴喷丁和度洛沙汀，并检查其抗异常性疼痛和抗神经瘤疼痛作用。吗啡、普瑞巴林、加巴喷丁和度洛沙汀以剂量依赖性方式减弱机械性异常性疼痛的水平。吗啡，而不是普瑞巴林，加巴喷丁和度洛沙汀，减轻神经瘤疼痛。吗啡对神经瘤疼痛的作用不如对机械性异常性疼痛的作用强。在两种药物联合研究（吗啡+普瑞巴林、吗啡+度洛沙坦和普瑞巴林+度洛沙坦）中，所有药物联合对机械性异常性疼痛产生协同作用，但对神经瘤疼痛无协同作用。这些数据表明，吗啡的效力和

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