Gabapentin produces antinociceptive effects on the spinal cord with simultaneous activation of descending facilitation in spinal nerve-ligated rats

Gabapentin has been proposed as one of several first-line agents to treat neuropathic pain. Although both spinal and supraspinal neuronal mechanisms participate in the antinociceptive effects of gabapentin, the supraspinal contribution to the effects of gabapentin at the spinal level remains unclear. We evaluated the role of descending modulation in the antinociceptive effects of gabapentin at the spinal level using continuous blockade of descending pathways in spinal nerve-ligated (SNL) rats. Tail flick (TF) latencies following sham operation or SNL operation were measured for 2 weeks. Rats were chronically implanted with both cervical and lumber intrathecal catheters, and a continuous cervical intrathecal infusion of 1% lidocaine was utilized for suppression of descending modulation. TF latencies following intrathecal administration of normal saline or 50 pg gabapentin were measured with/without descending modulation in SNL and sham-operated rats. TF latencies (percentage of the maximum possible effect) were significantly shortened in the 2 weeks following SNL operation. With descending modulation, intrathecal gabapentin did not prolong TF latencies in sham-operated rats, and prolonged TF latency only at the 60-min time point in SNL rats ; 28.9± 17.3% (p< 0.05 compared with baseline). Without descending modulation, intrathecal gabapentin to shamoperated rats slightly prolonged TF latencies at 15 and 30 min compared with the saline group of sham-operated rats, but intrathecal gabapentin to SNL rats resulted in significant prolongation of TF latencies ; 41.6+39.0% (p< 0.01) to 68.2+ 37.4% (p< 0.001). The results of this study indicate that gabapentin causes both apparent antinociception at the spinal level and simultaneous descending facilitation in neuropathic pain conditions.