Inhibition of the AMPK/PGC-1α/Mfn2 Axis is Associated with Mitochondria-ER Dysfunction and Ultrastructural Remodeling in a Rat Model of Myofascial Trigger Points.

Background: Myofascial trigger points (MTrPs) represent the primary pathological basis of myofascial pain syndrome (MPS). However, the exact cellular and molecular mechanisms underlying MTrPs formation and maintenance remain largely unknown, especially regarding mitochondrial function, endoplasmic reticulum (ER) homeostasis, and energy metabolism regulation. Methods: A rat model of MTrPs was established by blunt striking combined with eccentric exercise. ATPase histochemistry, immunofluorescence staining, transmission electron microscopy (TEM), Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to investigate muscle fiber type conversion, ultrastructural changes, and the expression levels of key molecules involved in mitochondrial energy metabolism. Results: Muscle fibers in the MTrPs model exhibited a phenotypic switch from type I to type II fibers. Ultrastructurally, the MTrPs region showed abnormalities, including swollen and vacuolar mitochondria with matrix rarefaction, dilated ER cisternae, and significantly increased mitochondria-ER contacts (MERCs). The AMPK/PGC-1α/Mfn2 signaling axis and MEF2 were significantly downregulated at both mRNA and protein levels. Conclusion: Mitochondrial-ER dysfunction, energy metabolism disturbance, and muscle ultrastructural remodeling are associated with the pathophysiology of MTrPs, and these alterations may be linked to the downregulation of the AMPK/PGC-1α/Mfn2 pathway. These findings provide support for the "energy crisis" hypothesis of MTrPs from both molecular and ultrastructural perspectives, and identify potential therapeutic targets for MPS.