Electroacupuncture alleviates Parkinson's disease-related pain by inhibiting microglial NLRP3-ASC inflammasome in the amygdala.

Abstract

This study aimed to investigate the role of microglia and NOD-like receptor protein 3 (NLRP3) inflammasome-mediated neuroimmune pathways in the analgesic effects of electroacupuncture (EA) in a mouse model of Parkinson's disease (PD). Male C57BL/6 mice (8 weeks old) were randomly assigned to the control, PD model, and PD + EA groups. PD was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), while control mice received saline. EA was administered to the motor cortex once daily for five consecutive days in the PD + EA group, whereas PD model mice were restrained without receiving EA stimulation. Behavioral assessments were performed to evaluate motor function and nociceptive sensitivity. Immunohistochemistry, immunofluorescence, and western blot analyses were used to quantify tyrosine hydroxylase (TH), ionized calcium-binding adapter molecule 1 (Iba-1), NLRP3 inflammasome components, and inflammatory cytokines in key brain regions. Compared with control mice, PD model mice showed reduced motor performance and heightened nociceptive sensitivity, accompanied by a decrease in TH-positive neurons and an increase in Iba-1-positive microglia in both the substantia nigra and amygdala. EA significantly improved motor performance and increased pain thresholds. Moreover, EA preserved TH-positive neurons, suppressed microglial activation, and downregulated the expression of NLRP3, ASC, caspase-1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the amygdala. These findings suggest that EA alleviates PD-related pain, possibly by modulating microglial activation and NLRP3 inflammasome signaling in the amygdala, thereby reducing neuroinflammation.