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

Chronic pain is a prevalent and debilitating non-motor symptom of Parkinson's disease (PD), significantly impairing patient quality of life and often proving refractory to conventional dopaminergic therapies. Emerging evidence highlights the critical role of neuroinflammation, particularly microglial activation and the NLRP3 inflammasome pathway, in both PD pathogenesis and the amplification of pain signals within specific brain regions. Understanding these neuroimmune mechanisms offers new avenues for therapeutic intervention. This study investigates electroacupuncture (EA) as a non-pharmacological approach to modulate this inflammatory cascade and alleviate PD-related pain.

Male C57BL/6 mice, 8 weeks old, were randomly assigned to control, PD model, and PD + EA groups. The Parkinson's disease model was induced via intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Control mice received saline. Electroacupuncture (EA) was administered to the motor cortex once daily for 5 consecutive days in the PD + EA group. Behavioral assessments evaluated 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 the substantia nigra and amygdala.

Compared to control mice, Parkinson's disease model mice exhibited reduced motor performance and heightened nociceptive sensitivity. This was accompanied by a decrease in TH-positive neurons and an increase in Iba-1-positive microglia in both the substantia nigra and amygdala. Electroacupuncture significantly improved motor performance and increased pain thresholds in the PD + EA group. Furthermore, EA preserved TH-positive neurons and suppressed microglial activation. In the amygdala, EA downregulated the expression of key inflammatory markers: NLRP3, ASC, caspase-1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. These findings strongly suggest that EA's analgesic effects are mediated by modulating microglial activation and the NLRP3 inflammasome signaling pathway in the amygdala.

Electroacupuncture significantly improved motor performance and increased pain thresholds in Parkinson's disease mice, while also preserving TH-positive neurons and suppressing microglial activation (Iba-1) and NLRP3 inflammasome components in the amygdala.