Tian Jie, Gu Yiwen, Su Diansan, Wu Yichao, Wang Xiangrui
Department of Anesthesiology, Renji Hospital, Medical School of Shanghai Jiaotong University, Shanghai, China.
Eur J Pain. 2009 Feb;13(2):130-7. doi: 10.1016/j.ejpain.2008.03.013. Epub 2008 May 16.
The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.
本研究调查了不同剂量鞘内注射利多卡因对神经病理性疼痛慢性压迫损伤模型中已建立的热痛觉过敏和触觉异常性疼痛的影响,确定了有效药物剂量范围、镇痛效果持续时间以及该治疗对身体和组织的影响。雄性Sprague-Dawley大鼠分为五组,在坐骨神经松结扎7天后接受鞘内注射生理盐水或利多卡因(2、6.5、15和35mg/kg)。结果发现,在鞘内治疗期间,随着利多卡因剂量的增加,呼吸抑制和血流动力学不稳定变得更加严重。接受35mg/kg利多卡因的组中有两只动物出现肺水肿并死亡。行为测试表明,鞘内注射6.5、15和35mg/kg利多卡因可不同程度地逆转热痛觉过敏,且持续2-8天,而2mg/kg利多卡因则无此效果。仅在接受15和35mg/kg利多卡因的大鼠中观察到对触觉异常性疼痛的抑制作用,且这两组的抗异常性疼痛效果相同。对脊髓的组织病理学检查显示,接受2-15mg/kg利多卡因的大鼠有轻度变化。然而,给予35mg/kg利多卡因后病变严重。这些发现表明,鞘内注射利多卡因对已建立的神经病理性疼痛具有延长的治疗作用。除35mg/kg外,在大多数情况下交感神经和副交感神经活动之间的平衡可以得到很好的维持。考虑到有益效果与副作用之间的比例,15mg/kg的剂量适合鞘内注射以缓解神经病理性疼痛。