Electroacupuncture Inhibited the Spinal Glial Activation in Neuropathic Pain via Glucagon-like Peptide-1/Glucagon-like Peptide-1 Receptor Signaling

Abstract

Background: The enhancement of glucagon-like peptide 1 (GLP-1)/GLP-1 receptor (GLP-1R) may be considered a novel therapeutic idea for neuropathic pain. Electroacupuncture (EA) has been widely used as an ideal nonpharmacological treatment for neuropathic pain, but the underlying mechanisms remain largely unknown. Therefore, we aim to explore whether repetitive EA stimulation could activate the spinal GLP-1/GLP-1R signaling in neuropathic pain. Materials and Methods: Paw withdrawal threshold and thermal withdrawal latency analyses were used to evaluate the effects of 2HZ/1 mA EA on pain-related behaviors of rats with spared nerve injury (SNI). Expressional levels of protein molecules in spinal dorsal horn were detected by Western blot and immunofluorescence staining. Results: Application of 2HZ/1 mA of EA at “ST36” and “SP6” effectively and persistently relieved nerve injury-induced pain hypersensitivity. Ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) were highly expressed in the ipsilateral spinal dorsal horn of SNI rats but inhibited by EA. In addition, EA increased the expression levels of GLP-1 and GLP-1R in the ipsilateral spinal dorsal horn. Pharmacological activation of GLP-1R mimicked the analgesic effects of EA on pain hypersensitivity, whereas blocking of GLP-1R reversed these effects. Conclusions: These results revealed that 2HZ/1 mA of EA at “ST36” and “SP6” alleviated nerve injury-induced pain hypersensitivity via mechanisms possibly involving enhancement of GLP-1/GLP-1R signaling, which further suppresses spinal glial activation.