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Patients with diabetic peripheral neuropathy experience debilitating pain that significantly affects their quality of life (Abbott et al., 2011), by causing sleeping disorders, anxiety, and depression (Dermanovic Dobrota et al., 2014). The primary clinical manifestation of painful diabetic neuropathy (PDN) is mechanical hypersensitivity, also known as mechanical allodynia (MA) (Callaghan et al., 2012). MA's underlying mechanism remains poorly understood, and so far, based on symptomatic treatment, it has no effective therapy (Moore et al., 2014).

Post-incision pain often occurs after surgery and is emergent to be treated in clinic. It hinders the rehabilitation of patients and easily leads to various types of postoperative complications. Acupuncture-combined anesthesia (ACA) is the combination of traditional acupuncture and modern anesthesia, which means acupuncture is applied at acupoints with general anesthesia. It was testified that ACA strengthened the analgesic effect and reduced the occurrence of postoperative pain, but its mechanism was not clear. Numerous reports have shown that chemokine receptor CX3CR1 is involved in the development and progression of many pathological pains. The present study was aimed to reveal whether ACA played the analgesic roles in the post-incision pain by affecting CX3CR1. A model of toe incision pain was established in C57BL/6J mice. The pain threshold was detected by behavioral test, and the expression of CX3CR1 protein was detected by immunohistochemical method and Western blot. The results showed that the significant mechanical allodynia and thermal hyperalgesia were induced by paw incision in the mice. Mechanical allodynia was significantly suppressed by ACA, but thermal hyperalgesia was not changed. CX3CR1 was mainly expressed in microglia in the spinal cord dorsal horn, and its protein level was significantly increased at 3 d after incision compared with that of naïve C57BL/6J mice. ACA did not affect CX3CR1 protein expression at 3 d after incision in the toe incision model mice. Paw withdrawal threshold was significantly increased at 3 d after incision in CX3CR1 knockout (KO) mice compared with that in the C57BL/6J mice. But the analgesic effect of ACA was disappeared in CX3CR1 KO mice. Accordingly, it was also blocked when neutralizing antibody of CX3CR1 was intrathecally injected (i.t.) 1 h before ACA in the C57BL/6J mice. These results suggest that CX3CR1 in microglia is involved in post-incision pain and analgesia of ACA.