Spinal Mechanism Underlying the Antiallodynic Effect of Gabapentin Studied in the Mouse Spinal Nerve Ligation Model

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  • Morimoto Shin-ichi
    Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan Advanced Medical Research Center, School of Medicine, Faculty of Medicine, Toho University, Japan Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan Advanced Medical Research Center, School of Medicine, Faculty of Medicine, Toho University, Japan
  • Ito Masanori
    Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan Advanced Medical Research Center, School of Medicine, Faculty of Medicine, Toho University, Japan Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan Advanced Medical Research Center, School of Medicine, Faculty of Medicine, Toho University, Japan
  • Oda Satoko
    Department of Anatomy, School of Medicine, Faculty of Medicine, Toho University, Japan Department of Anatomy, School of Medicine, Faculty of Medicine, Toho University, Japan
  • Sugiyama Atsushi
    Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan
  • Kuroda Masaru
    Department of Anatomy, School of Medicine, Faculty of Medicine, Toho University, Japan Department of Anatomy, School of Medicine, Faculty of Medicine, Toho University, Japan
  • Adachi-Akahane Satomi
    Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan Advanced Medical Research Center, School of Medicine, Faculty of Medicine, Toho University, Japan Department of Pharmacology, School of Medicine, Faculty of Medicine, Toho University, Japan Advanced Medical Research Center, School of Medicine, Faculty of Medicine, Toho University, Japan

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Abstract

We studied the antiallodynic effect of gabapentin (GBP) in the mouse model of neuropathic pain, aiming at clarifying the underlying mechanism. The L5 spinal nerve ligation induced tactile allodynia, an increase of CD11b expression, and an increase in the protein expression level of the voltage-dependent Ca2+ channel α2/δ-1 subunit in the spinal dorsal horn on the injured side. The chronic intrathecal administration of GBP (100 μg/body per day) as well as ω-conotoxin MVIIA, an N-type Ca2+-channel blocker, completely suppressed allodynia, but did not attenuate the CD11b expression. The antiallodynic effect of GBP lasted for several days after the termination of the drug, while that of ω-conotoxin MVIIA disappeared immediately after the termination. GBP suppressed the elevation of the protein level of the α2/δ-1 subunit in the spinal dorsal horn, although it did not affect its mRNA level in the L5 DRG. These results suggest that GBP inhibits the development of allodynia by suppressing the up-regulation of N-type Ca2+ channels, through normalization of the protein level of the α2/δ-1 subunit at the primary afferent nerve terminal via the inhibition of its anterograde transport. In addition, we propose that the nerve injury enhances the expression level of α2/δ-1 in the downstream of the activation of microglia.

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