Electroacupuncture Attenuates Fibromyalgia Pain Through Increased PD-1 Expression in Female Mice

Background/Objectives: Fibromyalgia causes chronic long-term pain, with symptoms lasting for months to years. Given the lack of evidence-based methods for diagnosing and assessing fibromyalgia, it ranks among the most difficult chronic pain conditions to treat. Programmed cell death ligand 1 (PD-L1) can inhibit acute and chronic pain transmission by inhibiting neuronal ion channels. Methods: Here, we aimed to explore the analgesic efficacy and mechanism of PD-L1/PD1 in an intermittent cold stress-induced fibromyalgia pain mouse model. Results: Von Frey and Hargreaves tests were performed, showing that the mouse model exhibited mechanical (day 4: 2.08 ± 0.13 g, n = 9) and thermal hyperalgesia (day 4: 3.93 ± 0.45 s, n = 9). Electroacupuncture (EA) or intraventricular PD-L1 injection effectively alleviated the nociceptive response and led to low PD-1 levels in the mouse dorsal root ganglia, spinal cord, thalamus, somatosensory cortex, and cerebellum, as measured through Western blots. In contrast, the pain-related kinase levels increased after fibromyalgia induction; these effects were reversed by EA and PD-L1 via the inhibition of microglia/astrocytes and Toll-like receptor 4. Conclusions: Our results show that EA can treat fibromyalgia pain in mice through effects on the PD-L1/PD1 pathway, indicating its potential as a therapeutic target in fibromyalgia.