ObjectiveTo study the analgesic mechanism of gabapentin, an anticonvulsant, during antinociceptive clinical treatment. MethodsWhole-cell voltage-clamp recordings were taken from adult rat spinal cord slices to investigate the effect of gabapentin on primary afferent Aδ-fiber evokedexcitatory postsynaptic currents (EPSCs) to substantia gelatinosa (SG) neurons in normal and inflamed (established by plantar injection of carrageenan) rats. Results Gabapentin (5-20 μmol/L for 5 min) depressed dorsal root Aδ fiber evoked polysynaptic, but not monosynaptic EPSCs to SG experiencing inflammation by about 25ptic or monosynaptic EPSCs in normal rats. Gabapentin failed to block a glutamate receptor subtype, N-methyl-D-aspartate (NMDA), -induced slow excitatory currents on SG neurons.ConclusionsInflammation, at least in part, unmasks the gabapentin depression on nociception transmission in the dorsal h, and this depression is not due to the blockade of postsynaptic NMDA receptor.