Yezierski Robert P, Green Megan, Murphy Karen, Vierck Charles J
Department of Orthodontics and the Comprehensive Center for Pain Research, University of Florida, Gainesville, Florida, USA.
Behav Pharmacol. 2013 Oct;24(7):598-609. doi: 10.1097/FBP.0b013e3283656d9b.
Neuropathic pain challenges healthcare professionals and researchers to develop new strategies of treatment and experimental models to better understand the pathophysiology of this condition. In the present study, the efficacy of gabapentin on thermal sensitivity following spinal nerve ligation and spinal cord compression was evaluated. The method of behavioral assessment was a well-validated cortically dependent operant escape task. Spinal nerve ligation produced peripheral neuropathic pain whereas spinal cord compression, achieved with an expanding polymer placed extradurally, produced a condition of central neuropathic pain. Changes in thermal sensitivity were also observed in animals undergoing nerve ligation surgery without nerve injury. Gabapentin (50 and 100 mg/kg) significantly reduced thermal sensitivity to 10 and 44.5 °C in surgically naive animals as well as those undergoing spinal nerve ligation and spinal cord compression. In conclusion, an operant method of behavioral assessment was used to show that spinal nerve ligation and spinal cord compression produced increases in sensitivity to noxious cold and heat stimuli. A decrease in thermal sensitivity was observed following administration of gabapentin. The results achieved with these methods are consistent with the clinical profile of gabapentin in treating conditions of neuropathic pain.
神经性疼痛促使医疗保健专业人员和研究人员开发新的治疗策略和实验模型,以更好地理解这种疾病的病理生理学。在本研究中,评估了加巴喷丁对脊髓神经结扎和脊髓压迫后热敏感性的疗效。行为评估方法是一种经过充分验证的皮质依赖性操作性逃避任务。脊髓神经结扎产生周围神经性疼痛,而通过硬膜外放置的膨胀聚合物实现的脊髓压迫则产生中枢神经性疼痛。在未发生神经损伤的神经结扎手术动物中也观察到了热敏感性的变化。加巴喷丁(50和100mg/kg)在未经手术的动物以及接受脊髓神经结扎和脊髓压迫的动物中,均显著降低了对10和44.5°C的热敏感性。总之,采用操作性行为评估方法表明,脊髓神经结扎和脊髓压迫会导致对有害冷刺激和热刺激的敏感性增加。给予加巴喷丁后观察到热敏感性降低。这些方法所取得的结果与加巴喷丁治疗神经性疼痛疾病的临床情况一致。