Spinal mechanism underlying the antiallodynic effect of gabapentin studied in the mouse spinal nerve ligation model

Shin-ichi Morimoto, Masanori Ito, Satoko Oda, Atsushi Sugiyama, Masaru Kuroda, Satomi Adachi-Akahane
Journal of Pharmacological Sciences 2012, 118 (4): 455-66
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 Ca(2+) channel α(2)/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 Ca(2+)-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 α(2)/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 Ca(2+) channels, through normalization of the protein level of the α(2)/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 α(2)/δ-1 in the downstream of the activation of microglia.

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