Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn

Abstract

We investigated the effects of gabapentin (GBP) on glutamatergic synaptic transmission in the dorsal horn of the rat spinal cord. Patch clamp whole cell recordings were made from superficial and deep dorsal horn neurons of rat spinal cord slices. In the majority of neurons in the superficial lamina, GBP decreased the amplitudes of evoked excitatory postsynaptic currents (evoked EPSCs) mediated by either non-NMDA or NMDA receptors. In contrast, neurons 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 increase 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 postsynaptic, spontaneous miniature excitatory postsynaptic currents (mEPSCs) were studied. In 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 receptor-mediated mEPSCs, the effect accompanied an increase in amplitude. These results suggest that GBP presynaptically inhibits glutamatergic synaptic transmission predominantly in the superficial lamina, while postsynaptically enhancing NMDA receptor-mediated transmission in some neurons of the deep lamina. The antinociceptive effects of GBP may involve the inhibition of the release of excitatory amino acids from presynaptic terminals.

Gabapentin reduces preoperative anxiety and pain catastrophizing in highly anxious patients prior to major surgery: a blinded randomized placebo-controlled trial

“…47 On the other hand, in healthy volunteers and studies involving patients with epilepsy, GABA levels were increased after oral ingestion of gabapentin. 48,49 Furthermore, gabapentin was found to inhibit both the excitatory synaptic transmission in vitro 50 and the neuronal response to noxious electrical and mechanical stimulation in vivo mediated by a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 51 and decrease glutamate levels in the rat brain. 52 The above human and rodent data suggest possible mechanisms underlying both the anxiolytic and sedative properties observed in this study.…”

Spinal Gabapentin and Antinociception: Mechanisms of Action

“…Although the antinociceptive mechanisms of spinal gabapentin remain unclear, several hypotheses have been suggested. It has been reported that gabapentin decreases glutamate concentrations and inhibits the release of glutamate and glutamatergic synaptic transmission presynatically (15)(16)(17). Glutamate acts on the NMDA receptor and non-NMDA receptor and shows the excitatory effect (18,19).…”

Advances in the therapy of cancer pain: from novel experimental models to evidence-based treatments

“…It is likely that the drug possesses a generic analgesic and antihyperalgesic effect by modifying channels involved in nociception (86,96) and neurotransmitter release (133). Confirmation from clinical studies, have shown that gabapentin is effective against pain in cancer patients, as well (134)(135)(136)(137)(138)(139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149).…”