Long-term oral eicosapentaenoic acid administration can ameliorate central fibromyalgia symptoms

Fibromyalgia is difficult to treat and often cause widespread musculoskeletal pain, leading to depression. We used intermittent cold stress to induce chronic pain and depression comorbidity (CPDC) in mice. CPDC mice exhibited chronic mechanical and thermal hyperalgesia, accompanied by depressive symptoms. Metabolomics results showed that eicosapentaenoic acid (EPA) has anti-inflammatory effects. Western blotting results revealed decreased programed cell death protein 1 (PD-1) receptor in the cerebellum of CPDC mice. However, there was significantly increased neuroinflammation due to higher protein levels in astrocyte and microglia, as well as their neurotransmitters high mobility group box 1, S100 calcium binding protein B, and toll-like receptor 4 receptor signaling. EPA administration can prevent CPDC by increasing PD-1 expression and inhibiting inflammation-related pathways. Similar results were also observed in transient receptor potential vanilloid 1 knockout mice. In conclusion, long-term oral EPA administration can prevent CPDC by increasing PD-1 in the cerebellum and inhibiting neuroinflammatory pathways.