Background
Paclitaxel-induced peripheral neuropathy (PIPN) is prevalent among patients receiving paclitaxel chemotherapy, which
Conclusions
These findings suggest EA alleviates PIPN by reducing CCL2/CCR2 mediated-pro-inflammatory macrophage infiltration into sensory ganglia as well as the sciatic nerve. Our study supports EA could be used as a potential non-pharmacological therapy for PIPN.
Methods
A mouse model of PIPN was established by repeated paclitaxel application. Electroacupuncture (EA) was applied at ST36 and BL60 acupoints of model mice. Immunostaining, flow cytometry, behavioral assay, in vivo imaging were utilized for effects determination and mechanism exploration.
Results
EA ameliorated mechanical and cold pain hypersensitivities, reduced sensory neuron damage and improved loss in intra-epidermal nerve fibers (IENFs) in model mice. Macrophages infiltration were detected in DRG and sciatic nerve of model mice, which was reduced by EA. EA affected M1-like pro-inflammatory macrophage infiltration in DRG, whereas it did not affect M2-like macrophages. DRG neurons released chemoattractant CCL2 that recruited macrophages via CCR2 to DRG. EA reduced CCL2 overproduction by DRG neurons and reduced macrophage infiltration. Blocking CCR2 mimicked EA's anti-allodynic effect, whereas exogenously applying recombinant CCL2 reversed the ameliorative effect of EA on macrophage infiltration and abolished EA's anti-allodynia on model mice. EA ameliorated other signs of PIPN, including sensory neuron damage, sciatic nerve morphology impairment and IENFs loss. In mice inoculated with breast cancer cells, EA didn't affect paclitaxel-induced antitumor effect. Conclusions: These findings suggest EA alleviates PIPN by reducing CCL2/CCR2 mediated-pro-inflammatory macrophage infiltration into sensory ganglia as well as the sciatic nerve. Our study supports EA could be used as a potential non-pharmacological therapy for PIPN.