Isorhamnetin alleviates fibromyalgia-like pain and mood deficits via monoaminergic, inflammatory, and TRPV1 pathways in mice.

BACKGROUND

Fibromyalgia is a complex chronic pain syndrome frequently associated with mood disturbances. Current treatments are unsatisfactory, and it is important to develop new agents with multi-modal effects.

METHODS

Isorhamnetin was assessed in male Swiss Albino (8–10 weeks old) mice using a reserpine-induced fibromyalgia-like (reserpine 1 mg/kg, s.c., once daily for 3 consecutive days), and evaluated behavioral outcomes and mechanistic biomarkers following oral isorhamnetin (50–150 mg/kg; administered after fibromyalgia induction, with assessments performed over the subsequent hours).

RESULTS

Reserpine administration was characterized by the development of mechanical allodynia, muscle weakness, thermal hyperalgesia, and depressive-like immobility, exhaustive swimming, as well as anxiogenic thigmotaxis. These deficits were dramatically reversed by oral administration of isorhamnetin (50–150 mg/kg) in a dose-dependent manner (mechanical PWT: F(4,25) = 112.3, p < 0.001, η²=0.88; muscle strength: F(2,15) = 36.7, p < 0.001, η²=0.83; FST immobility: F(3,20) = 28.9, p < 0.001, η²=0.81). Isorhamnetin also restored levels of spinal serotonin, norepinephrine, and glutamate, as well as monoamine oxidase (MAO) activity. Moreover, it decreased levels of proinflammatory cytokines (IL-1β, TNF-α) and glial activation markers (Iba1, GFAP), as well as TRPV1 expression in the spinal dorsal horn.

CONCLUSION

These results indicate that isorhamnetin induces multifunctional therapeutic actions normalizing monoaminergic function and reducing excitotoxicity, neuroinflammation, glial activation, and TRPV1 signaling, pointing to it as a candidate for fibromyalgia drug development.