Evaluation of scopoletin as a potential therapeutic agent in fibromyalgia: evidence from a reserpine-induced mouse model

Fibromyalgia is a nociplastic pain disorder with musculoskeletal pain. Current treatments are frequently ineffective and produce unwanted side effects. Antinociceptive and neuroprotective activities of scopoletin have not yet been tested in fibromyalgia models. A mouse model of fibromyalgia was created by subcutaneous reserpine (1 mg/kg/d) administration for 3 successive days. Scopoletin treatment was initiated on day 4. Behavioral tests included the tests for mechanical allodynia (von Frey test), thermal hyperalgesia (Hargreaves test), and grip strength, as well as the forced swim test and the open field test. Toxicity was examined with the rotarod test, locomotor activity, catalepsy, body weight, and temperature. Reference drugs were pregabalin and duloxetine. Reserpine-induced significant mechanical allodynia (P < 0.001), thermal hyperalgesia (P < 0.001), muscle weakness (P < 0.001), depressive-like behavior (P < 0.001), and anxiety-like behavior (P < 0.01). Scopoletin (100 mg/kg) significantly reversed mechanical allodynia at 1 h posttreatment (P < 0.001) and improved grip strength (P < 0.01) and thermal latency (P < 0.01). It also reduced immobility in the FST by 37 ± 8% (P < 0.01) and decreased thigmotaxis in the open field test (P < 0.01). Unlike duloxetine, scopoletin significantly attenuated both depressive and anxiety-like behaviors. No significant changes in locomotor coordination, body weight, temperature, or catalepsy were observed (P > 0.05). Scopoletin demonstrated significant antinociceptive, antidepressant, and anxiolytic effects in a reserpine-induced fibromyalgia model.