Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn.
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.
Shimoyama
Megumi
M
Department of Physiology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi 260-8670, Japan Department of Pain Medicine and Palliative Care, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan Department of Physiology, Dokkyo University School of Medicine, 880 Ooazakitakobayashi, Mibu-cho, Shimotsuga-gun, Tochigi-ken, Japan.
Shimoyama
Naohito
N
Hori
Yuuichi
Y
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D000077206:Gabapentin; D018698:Glutamic Acid / Q000502:physiology*; D066298:In Vitro Techniques; D009475:Neurons, Afferent / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin