Mao J, Hayes R L, Price D D, Coghill R C, Lu J, Mayer D J
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Brain Res. 1992 Jul 3;584(1-2):18-27. doi: 10.1016/0006-8993(92)90873-8.
In a rat model of painful peripheral mononeuropathy, this study examined the effects of post-injury treatment with a monosialoganglioside, GM1, on abnormal nociceptive behaviors and spinal cord neural activity resulting from loose ligation of the rat common sciatic nerve (chronic constrictive injury, CCI). Thermal hyperalgesia and spontaneous pain behaviors of CCI rats were assessed by measuring foot-withdrawal latencies to radiant heat and by rating spontaneous hind paw guarding positions, respectively. Neural activity within different regions of the spinal cord was inferred in both CCI and sham-operated rats by employing the [14C]-2-deoxyglucose (2-DG) autoradiographic technique to measure spinal cord glucose metabolism. Intraperitoneal (i.p.) GM1 treatment (10 mg/kg) initiated 1 h or 24 h after injury and once daily for the first 9 post-injury days reduced thermal hyperalgesia of the hind paw ipsilateral to nerve ligation and lowered spontaneous pain behavior rating scores in CCI rats. Sciatic nerve ligation reliably increased basal 2-DG metabolic activity of CCI rats in all four sampled regions (laminae I-IV, V-VI, VII, VIII-IX) of spinal cord lumbar segments (L2-L5) both ipsilateral and contralateral to nerve ligation 10 days after injury. Consistent with the drug's effects on spontaneous pain behaviors, 10 daily GM1 treatments (10 mg/kg, i.p.) initiated 1 h after nerve ligation reduced spinal cord 2-DG metabolic activity in laminae V-VI and VII ipsilateral to nerve ligation and in all four sampled regions contralateral to nerve ligation. This attenuation of the increased spinal cord glucose utilization that occurs in the absence of overt peripheral stimulation may reflect an influence of GM1 on increased neural activity contributing to spontaneous pain. Since gangliosides are thought to protect neurons from excitotoxic effects of excitatory amino acids, these results suggest that ganglioside treatment may result in attenuation of excitatory neurotoxicity that may occur following peripheral nerve injury. Thus, ganglioside treatment could provide a new approach to the clinical management of neuropathic pain syndromes following peripheral nerve injury.
在疼痛性周围单神经病大鼠模型中，本研究检测了损伤后用单唾液酸神经节苷脂GM1治疗对大鼠坐骨神经松结扎（慢性压迫性损伤，CCI）所致异常伤害性反应行为和脊髓神经活动的影响。分别通过测量对辐射热的缩足潜伏期和对自发后足保护姿势进行评分，评估CCI大鼠的热痛觉过敏和自发疼痛行为。采用[14C]-2-脱氧葡萄糖（2-DG）放射自显影技术测量脊髓葡萄糖代谢，推断CCI大鼠和假手术大鼠脊髓不同区域的神经活动。损伤后1小时或24小时开始腹腔注射（i.p.）GM1（10mg/kg），并在损伤后的前9天每天注射一次，可减轻神经结扎同侧后足的热痛觉过敏，并降低CCI大鼠的自发疼痛行为评分。坐骨神经结扎可靠地增加了损伤后10天神经结扎同侧和对侧脊髓腰段（L2-L5）所有四个采样区域（I-IV层、V-VI层、VII层、VIII-IX层）CCI大鼠的基础2-DG代谢活性。与药物对自发疼痛行为的影响一致，神经结扎后1小时开始连续10天腹腔注射GM1（10mg/kg），可降低神经结扎同侧V-VI层和VII层以及神经结扎对侧所有四个采样区域的脊髓2-DG代谢活性。在无明显外周刺激情况下发生的脊髓葡萄糖利用增加的这种减弱，可能反映了GM1对导致自发疼痛的神经活动增加的影响。由于神经节苷脂被认为可保护神经元免受兴奋性氨基酸的兴奋毒性作用，这些结果表明神经节苷脂治疗可能会减轻外周神经损伤后可能发生的兴奋性神经毒性。因此神经节苷脂治疗可为外周神经损伤后神经性疼痛综合征的临床管理提供一种新方法。
