Qian J, Brown S D, Carlton S M
Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-1069, USA.
Brain Res. 1996 Apr 9;715(1-2):51-62. doi: 10.1016/0006-8993(95)01452-7.
The efficacy of ketamine (KET), a non-competitive NMDA receptor-channel blocker, was assessed in relieving nociceptive behaviors in neuropathic rats with tight ligations of the L5 and L6 spinal nerves. The antinociceptive effects of KET were dose- and time-dependent. A systemic injection of 0.01 mg/kg KET transiently (15-30 min) attenuated several nociceptive behaviors, including mechanical allodynia and hyperalgesia, cold allodynia, spontaneous pain, and cold stress-induced pain. Treatment with 1.0 mg/kg KET consistently decreased all nociceptive behaviors for 45-75 min, without noticeable side effects. Higher doses (25 and 50 mg/kg) provided longer lasting relief: however, these doses resulted in transient motor impairment which lasted for 15-30 min post-injection. Systemic KET was most effective in decreasing the behavioral signs of mechanical allodynia and hyperalgesia, followed by cold allodynia, cold stress-induced pain, and spontaneous pain. The present results demonstrate that blockade of NMDA receptors effectively alleviates nociceptive behaviors in a rat model of peripheral neuropathy, substantiating the important role of these receptors in the central sensitization that underlies the maintenance of neuropathic pain. In addition, the ability of KET to reduce significantly a variety of nocifensive behaviors suggests that this clinically safe drug could be used in pain management for neuropathic patients.
非竞争性N-甲基-D-天冬氨酸（NMDA）受体通道阻滞剂氯胺酮（KET）对L5和L6脊神经紧密结扎所致神经性大鼠伤害性反应行为的缓解作用进行了评估。KET的抗伤害感受作用具有剂量和时间依赖性。全身注射0.01mg/kg KET可短暂（15 - 30分钟）减轻多种伤害性反应行为，包括机械性异常性疼痛和痛觉过敏、冷异常性疼痛、自发性疼痛以及冷应激诱导的疼痛。1.0mg/kg KET治疗可使所有伤害性反应行为持续降低45 - 75分钟，且无明显副作用。更高剂量（25和50mg/kg）可提供更持久的缓解：然而，这些剂量会导致短暂的运动功能障碍，注射后持续15 - 30分钟。全身应用KET对减轻机械性异常性疼痛和痛觉过敏的行为学表现最为有效，其次是冷异常性疼痛、冷应激诱导的疼痛和自发性疼痛。目前的结果表明，阻断NMDA受体可有效减轻周围神经病变大鼠模型中的伤害性反应行为，证实了这些受体在构成神经性疼痛维持基础的中枢敏化中的重要作用。此外，KET显著降低多种伤害性反应行为的能力表明，这种临床安全药物可用于神经性疼痛患者的疼痛管理。
