• Rie Matsuzawa, Tomonori Fujiwara, Kohei Nemoto, Teruyuki Fukushima, Shigeki Yamaguchi, Kimio Akagawa, and Yuuichi Hori.
• Department of Physiology and Biological Information, Dokkyo Medical University, Kitakobayashi 880, Mibu, Tochigi 321-0293, Japan.
• Neurosci. Lett. 2014 Jan 13; 558: 186-91.

AbstractPregabalin is widely used as an analgesic for the treatment of neuropathic pain. In the present experiments using mouse spinal slices, we recorded electrically evoked glutamatergic excitatory postsynaptic currents (eEPSCs) from superficial dorsal horn neurons. Pregabalin reduced the amplitude of eEPSCs, and increased the paired pulse ratio. Pregabalin also inhibited the frequency of spontaneously occurring miniature EPSCs without affecting their amplitude. Partial ligation of the sciatic nerve increased the expression of the calcium channel α2δ-1 subunit, and increased the presynaptic inhibitory action of pregabalin. Intrathecal injection of antisense oligodeoxynucleotide against the α2δ-1 subunit, decreased the expression of α2δ-1 mRNA in the spinal dorsal horn, and decreased pregabalin's action. These results provide further evidence that pregabalin exerts its presynaptic inhibitory action via binding with the α2δ subunit in a state-dependent manner. Furthermore, presynaptic actions of pregabalin were attenuated in knockout mice lacking the protein syntaxin 1A, a component of the synaptic vesicle release machinery, indicating that syntaxin 1A is required for pregabalin to exert its full presynaptic inhibitory action. These observations might suggest that direct and/or indirect interactions with the presynaptic proteins composing the release machinery underlie at least some part of pregabalin's presynaptic actions.Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

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