Panax ginseng Extract Improves Fibromyalgialike Symptoms in Mice: Involvement of Hippocampal BDNF–CREB Signaling

Background: Fibromyalgia affects 2%–4% of the population with limited treatment options. Panax ginseng C. A. Meyer has been used traditionally for stress-related disorders, but the mechanisms are not well understood. Objectives: To examine the effects of standardized P. ginseng extract on fibromyalgia-like symptoms and molecular pathways in mice. Materials and Methods: C57BL/6J mice underwent combined chronic restraint stress and intermittent cold stress to induce fibromyalgia-like symptoms. Animals received daily oral P. ginseng extract (300 mg/kg) or vehicle for 23 days. We measured mechanical allodynia, thermal hyperalgesia, and depression-like behavior. Serum corticosterone and hippocampal brain-derived neurotrophic factor (BDNF)–CREB signaling were analyzed. Results: The standardized extract contained ginsenosides Re (8.4 mg/g), Rc (6.2 mg/g), Rd (4.1 mg/g), Rb1 (3.7 mg/g), and Rf (1.6 mg/g). Treatment improved mechanical allodynia (paw withdrawal threshold: 2.1 ± 0.3 g to 4.8 ± 0.4 g, p < .001), thermal hyperalgesia (latency: 8.2 ± 0.7 s to 14.6 ± 1.1 s, p < .001), and depression-like behavior (immobility time: 187 ± 15 s to 121 ± 12 s, p < .005). Elevated serum corticosterone was normalized (421 ± 38 pg/mL to 298 ± 25 pg/mL, p < .05). Molecular analysis showed restoration of hippocampal BDNF expression and CREB phosphorylation (both p < .001). Conclusion: Standardized P. ginseng extract improves fibromyalgia-like symptoms in mice, potentially mediated by modulation of hippocampal BDNF–CREB signaling. These results help explain the traditional use of ginseng in stress-related pain conditions.