Systemic ketamine attenuates nociceptive behaviors in a rat model of peripheral neuropathy

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.