Synergistic effect between intrathecal non-NMDA antagonist and gabapentin on allodynia induced by spinal nerve ligation in rats

Background: Glutamate and non-N-methyl-D-aspartate (NMDA) receptors have be en implicated in the development of neuroplasticity in the spinal cord in n europathic pain. The spinal cord has been identified as one of the sites of the analgesic action of gabapentin. In the current study, the authors dete rmined the antiallodynic effect of intrathecal 6-cyano-7-nitroquinoxaline-2 ,3-dione (CNQX) in a rat model of neuropathic pain. Also tested was a hypot hesis that Intrathecal injection of CNQX and gabapentin produces a synergis tic effect on allodynia in neuropathic rats. Methods: Allodynia was produced in rats by ligation of the left L5 and L6 s pinal nerves. Allodynia was determined by application of von Frey filaments to the left hind paw. Through an implanted intrathecal catheter, 10-100 mu g gabapentin or 0.5-8 mu g CNQX disodium (a water-soluble formulation of C NQX) was injected in conscious rats. Isobolographic analysis was performed comparing the interaction of intrathecal gabapentin and CNQX using the ED50 dose ratio of 15:1. Results: Intrathecal treatment with gabapentin or CNQX produced a dose-depe ndent increase in the withdrawal threshold to mechanical stimulation. The E D50 for gabapentin and CNQX was 45.9 +/- 4.65 and 3.4 +/- 0.22 mu g, respec tively. Intrathecal injection of a combination of CNQX and gabapentin produ ced a strong synergistic antiallodynic effect in neuropathic rats. Conclusions: This study shows that intrathecal administration of CNQX exhib its an antiallodynic effect in this rat model of neuropathic pain. Furtherm ore, CNQX and gabapentin, when combined intrathecally, produce a potent syn ergistic antiallodynic effect on neuropathic pain in spinal nerve-ligated r ats.