Eicosapentaenoic acid reduces fibromyalgia pain by inhibiting the microglia/astrocyte and toll-like receptor 4 pathway in the mouse brain

The role of eicosapentaenoic acid (EPA) in fibromyalgia (FM) pain are limited. FM, defined as pain that persists for several months, is an increasing medical challenge with significant implications for patients, the economy, and society. A FM pain mouse model was performed using intermittent cold stress (ICS). Mechanical (2.07 ± 0.12 g) and thermal (4.55 ± 0.36 s) hyperalgesia was initiated after ICS induction in the FM pain mouse model. Results showed that the detrimental effects of ICS were relieved via the oral administration of EPA (100 mg/kg/day, 3.52 ± 0.12 g and 7.11 ± 0.37 s). The overexpression of the microglia, astrocyte, and toll-like receptor 4 signaling pathways was found in the nociceptive ascending pathway of FM mice, including the thalamus, somatosensory cortex, anterior cingulate cortex, and medial prefrontal cortex, which is associated with FM initiation. These phenomena could be further attenuated by EPA administration. EPA intake can be beneficial for FM management. • Oral administration of EPA relieved mice fibromyalgia pain. • Microglia/astrocyte and TLR4 pathways were greatly increased in thalamus, SSC, ACC, and mPFC of fibromyalgia mice. • EPA attenuated microglia/astrocyte and TLR4 signaling pathways.