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

Abstract

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 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.

Effects of Adjuvant Analgesics on Cerebral Ischemia-Induced Mechanical Allodynia

“…[36][37][38][39] Furthermore, gabapentin (10 and 30 mg/kg) dose-dependently decreased cold hypersensitivity, with a statistically significant difference observed at 30 mg/kg. 14) In clinical study, it was found that gabapentin is considered as a first line therapy or as add-on therapy for suppressing the pain behavior in CPSP patients.…”

Persistent Hyperalgesia in the Cisplatin-Treated Mouse as Defined by Threshold Measures, the Conditioned Place Preference Paradigm, and Changes in Dorsal Root Ganglia Activated Transcription Factor 3

“…30,31 Gabapentin acts by binding to the alpha2delta subunit of the calcium channel. This drug has efficacy in allodynia, which occurs after nerve injury 32 or chronic inflammation. 16,33 Ketorolac and etanercept have been shown to have effects in models of inflammatory hyperalgesia.…”

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice

“…4D: non-targeting siRNA-vehicle, n = 3; non-targeting siRNA-gabapentin 30 lg, n = 3; non-targeting siRNA-gabapentin 100 lg, n = 3; Cx43 siRNA-vehicle, n = 4; Cx43 siRNA-gabapentin 30 lg, n = 4; Cx43 siRNA-gabapentin 100 lg, n = 4; total number of mice = 21). Intrathecal doses of these drugs were determined based on previous studies (Akiyama et al, 2014;Chen et al, 2014;Morimoto et al, 2012;Tan-No et al, 2000;Tian et al, 2011).…”