Botulinum toxin type A relieve neuropathic pain by suppressing the expression of CXCL13/CXCR5 and GAT-1 in chronic constriction injury rats

Abstract

Botulinum toxin type A (BTX-A) was widely used to treat neuropathic pain in clinic. The underlying analgesic mechanism of BTX-A involves in axonal transport. The chemokine (C-X-C motif) ligand 13 (CXCL13) and GABA transporter 1 (GAT-1) played important roles in chronic pain. We established a chronic constriction injury (CCI) model. The pain behaviors of rats were measured by testing paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs). The level of proteins was measured by western blots. In our results, the CCI rats showed decrease of PWTs and PWLs, which were relieved by BTX-A. BTX-A reversed the over-expression of CXCL13 and GAT-1 in spinal cord, DRG, sciatic nerve and plantar in CCI rats and characterized in dose-dependent manner. The inhibition of BTX-A on proteins we examined didn’t show significant trend among time points. The analgesic effect of BTX-A disappeared after the axon transport of sciatic nerve blocked by the colchicine. But the PWTs of the colchicine treated CCI rats were higher than non- colchicine-treated CCI rats. Colchicine decreased the levels of CXCL13 and GAT-1 in CCI rats. What’s more, the proteins we examined peaked at the sciatic nerve in the non-colchicine group, but the phenomenon disappeared in the colchicine group. In conclusion, the BTX-A and colchicine relieve neuropathic pain and suppress the increase of CXCL13 and GAT-1. Colchicine prevents the analgesic effect of BTX-A by blocking axon transport. The axon transport may play roles in the peripheral mechanisms of neuropathic pain.

Spinal Cord Injury Provoked Neuropathic Pain and Spasticity, and Their GABAergic Connection

“…75 A recent study reports that BTX reduces the expression of upregulated CXCL13 and GAT-1 in NP chronic constriction injury (CCI) rat models. 76 Presently, lack of studies, low patient numbers, and lack of standardized optimum dose and delivery are the shortcomings that need sound research for BTX approval in NP post-SCI. 74 Already an approved drug for amyotrophic lateral sclerosis, riluzole reduced below-level cutaneous hypersensitivity in SCI-NP rats by inhibiting the glutamatergic transmission (Table 1).…”

“…Results from a randomized, double-blind placebo-controlled trial suggested that BTX decreased post-SCI pain intensity in patients at weeks 4 and 8 ( Table 2 ) [ 75 ]. A recent study reports that BTX reduces the expression of upregulated CXCL13 and GAT-1 in NP chronic constriction injury (CCI) rat models [ 76 ]. Presently, lack of studies, low patient numbers, and lack of standardized optimum dose and delivery are the shortcomings that need sound research for BTX approval in NP post-SCI [ 74 ].…”