Viable exogenous mitochondria modulate neurochemical and behavioral features of fibromyalgia in a reserpine-induced fibromyalgia model

Abstract

Fibromyalgia Syndrome (FMS) is a chronic disorder marked by widespread pain, fatigue, and cognitive dysfunction, often associated with mitochondrial dysfunction and oxidative stress. Despite existing treatments, none address the underlying mitochondrial defects. This study investigates the potential of viable exogenous mitochondria, isolated from H9C2 (2-1) myocardial cells, as a preclinical therapeutic and regenerative intervention for FMS in a reserpine-induced fibromyalgia rat model. Three doses (0.15, 0.5, and 1.5 mg/kg) of mitochondria were prepared and characterized using electron microscopy, dynamic light scattering, and flow cytometry for their integrity and viability. The different doses were intravenously administered in reserpine-induced FM female rats to determine the optimal therapeutic dosage. Key findings demonstrated dose-dependent effects on FM-related markers such as nociceptive response latency, blood serum assays, oxidative stress biomarkers, and neurotransmitter levels. A biodistribution study revealed preferential accumulation of mitochondria in affected tissues, such as the brain and soleus muscle, suggesting targeted delivery and potential regenerative effects. These findings provide preliminary preclinical evidence supporting mitochondrial transplantation as a novel and effective regenerative therapy for addressing mitochondrial dysfunction in fibromyalgia, suggesting a promising direction for future research on interventions targeting chronic pain and metabolic dysfunction.