Gabapentin produces PKA-dependent pre-synaptic inhibition of GABAergic synaptic transmission in LC neurons following partial nerve injury in mice

Journal of Neurochemistry
Keiko TakasuMitsuo Tanabe

Abstract

We have previously demonstrated that gabapentin supraspinally activates the descending noradrenergic system to ameliorate pain hypersensitivity in mice with partial nerve ligation. To clarify the supraspinal mechanism of action of gabapentin, whole-cell patch-clamp recordings were performed on locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury or mice subjected to a sham-operation, and the effects of gabapentin in the modulation of synaptic transmission were studied. Bath application of gabapentin (10, 30 and 100 muM) in a concentration-dependent manner reduced the GABA(A) receptor-mediated inhibitory post-synaptic currents (IPSCs) in slices prepared from partially nerve-ligated mice, whereas glutamate-mediated excitatory post-synaptic currents were hardly affected. By contrast, gabapentin did not reduce IPSCs in slices taken from mice given a sham operation. Although gabapentin altered neither the amplitude nor the frequency of miniature IPSCs, it reduced IPSCs together with an increase in the paired-pulse ratio, suggesting that gabapentin acts on the pre-synaptic GABAergic nerve terminals in the LC. As the protein kinase A (PKA) inhibitor H-89 but not the protein kinase C inhibit...Continue Reading

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Citations

Feb 26, 2013·Archives of Pharmacal Research·Ankesh KukkarAmteshwar Singh Jaggi
Dec 17, 2009·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Mitsuo TanabeHideki Ono
Jul 11, 2014·European Journal of Pharmacology·Chien-Hsing Lee, Horng-Huei Liou
Mar 17, 2009·European Journal of Pharmacology·Mitsuo TanabeHideki Ono
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