Botulinum toxin type A promotes microglial M2 polarization and suppresses chronic constriction injury-induced neuropathic pain through the P2X7 receptor

Xianwei Gui,Hansen Wang,Wei Wu,Heqing Zheng,Lanxiang Wu,Xuan Wang,Sheng Tian

doi:10.1186/s13578-020-00405-3

Xianwei Gui, Hansen Wang + Show 5 more

Open Access

https://doi.org/10.1186/s13578-020-00405-3

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Abstract

BackgroundSwitching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for neuropathic pain (NP). This study aims to investigate whether botulinum toxin type A (BTX-A) regulates microglial M1/M2 polarization by inhibiting P2X7 expression in a rat model of NP.ResultsThe BTX-A administration elevated pain threshold, induced microglial polarization toward the M2 phenotype, and decreased P2X7 protein level in a rat model of NP induced by chronic compression injury (CCI). Lipopolysaccharide (LPS) was used to activate HAPI rat microglial cells as an in vitro inflammatory model and we demonstrated that BTX-A promoted microglial M2 polarization in LPS-stimulated HAPI microglial cells through suppressing P2X7.ConclusionsOur results indicate that BTX-A promotes microglial M2 polarization and suppresses CCI-induced NP through inhibiting P2X7 receptor. These findings provide new insights into the mechanism of BTX-A in relieving NP.

Highlights

Switching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for neuropathic pain (NP)
BTX‐A elevated pain threshold and promoted microglial polarization toward the M2 phenotype in NP rats Compared with the sham-operated group, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values were significantly decreased in the NP group
MWT and TWL values were notably elevated in both botulinum toxin type A (BTX-A)-10 group and BTX-A-20 group when compared with the NP group, indicating that BTX-A administration elevated rat pain threshold postCCI (Fig. 1a, b)

Summary

Introduction

Switching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for neuropathic pain (NP). Microglia activation and subsequent pro-inflammatory responses play an important role in the development of NP [6]. Microglia can be activated in a polarizing manner into a classical phenotype (pro-inflammatory, M1) or an alternative phenotype (anti-inflammatory, M2). The M2 phenotype is characterized by increased expression of several proteins such as arginase-1 (Arg-1) and mannose receptor (MR/CD206), as well as increased production of antiinflammatory cytokines such as IL-4 and IL-10 [5, 9]. The microglial polarization toward the pro-inflammatory M1 phenotype often occurs during NP. Convincing evidence has indicated that modulation of inflammation by inhibition of M1 polarization can be a strategy for treatment of NP [10,11,12,13]

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