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

[BACKGROUND] Switching 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.

[RESULTS] The 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.

[CONCLUSIONS] Our 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.