Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn

We investigated the effects of gabapentin (GBP) on glutamatergic synaptic t ransmission in the dorsal horn of the rat spinal cord. Patch clamp whole ce ll recordings were made from superficial and deep dorsal horn neurons of ra t spinal cord slices. In the majority of neurons in the superficial lamina, GBP decreased the amplitudes of evoked excitatory postsynaptic currents (e voked EPSCs) mediated by either non-NMDA or NMDA receptors. In contrast, ne urons in the deep lamina showed variable effects, with a lower incidence of decrease in amplitude of evoked EPSCs and a subset of neurons showing an i ncrease in amplitude of evoked NMDA receptor-mediated EPSCs. No enhancement of evoked non-NMDA receptor-mediated EPSCs was observed in either lamina. To determine whether the observed effects of GBP are presynaptic and/or pos tsynaptic, spontaneous miniature excitatory postsynaptic currents (mEPSCs) were studied. Tn neurons that showed a decrease in its frequency of mEPSCs by GBP, no change in the amplitude or shape accompanied the effect. On the other hand, in neurons that showed an increase in the frequency of NMDA rec eptor-mediated mEPSCs, the effect accompanied an increase in amplitude. The se results suggest that GBP presynaptically inhibits glutamatergic synaptic transmission predominantly in the superficial lamina, while postsynaptical ly enhancing NMDA receptor-mediated transmission in some neurons of the dee p lamina. The antinociceptive effects of GBP may involve the inhibition of the release of excitatory amino acids from presynaptic terminals. (C) 2000 International Association for the Study of Pain. Published by Elsevier Scie nce B.V. All rights reserved.