Electroacupuncture Regulates Macrophage Polarization to Alleviate the Neuropathic Pain Induced by Spared Nerve Injury

The current therapeutic strategies for neuropathic pain have limited efficacy. The activation of macrophages and pro-inflammatory responses following peripheral nerve injury can effectively prevent the progression of neuropathic pain. Macrophage polarization to the M2 or M1 (respectively anti- and pro- inflammatory) phenotypes frequently occurs during neuroinflammation. Electroacupuncture (EA) therapy has been shown to exert anti-inflammatory functions in several pain models, and has thus been applied to alleviate neuropathic pain. Therefore, the present study aimed to determine whether EA could reduce neuroinflammation and induce analgesia by regulating macrophage polarization.

Forty-five male rats were used to create a spared nerve injury (SNI) model of peripheral nerve injury. Subsequently, EA was applied to the ipsilateral huantiao (GB30) and yanglingquan (GB34), and the von Frey assay was conducted to monitor the effect of EA on the paw withdrawal threshold. Immunofluorescence analyses were further performed to detect the effects of EA on interleukin-1β (IL-1β) expression and peripheral macrophage polarization.

EA attenuated pain behavior (P=0.002) and decreased inflammatory cytokines derived from macrophages (P=0.002 in the sciatic nerve; P=0.002 in the dorsal root ganglion, DRG) but not in Schwann (P>0.05) or mast (P>0.05) cells in SNI rats. In addition, EA increased M2 macrophage polarization (P<0.0001 in the sciatic nerve; P=0.001 in the DRG) and decreased M1 macrophage expression (P=0.036 in the sciatic nerve; P=0.022 in the DRG).

These data revealed that EA exerted analgesia by adjusting the polarization of macrophages and inhibiting the IL-1β expressing in macrophages in SNI rats.