Inhibition of Peripheral ERK Signaling Ameliorates Persistent Muscle Pain Around Trigger Points in Rats.

The purpose of this study was to investigate whether the ERK signaling pathway was involved in ameliorating chronic myofascial hyperalgesia from contused gastrocnemius muscle in rats. We established an animal model associated with myofascial pain syndrome and described the mechanism of muscle pain in an animal model. Changes in the mechanical pain threshold were observed 0.5, 1, 2, 3, 4, 5, 8, 12, 18, and 24 h after ERK inhibitor injection around myofascial trigger points (MTrPs) of the gastrocnemius muscle in rats. Morphological changes in gastrocnemius muscle cells were observed by hematoxylin and eosin (H&E) staining. ERK signaling pathway activation was detected through immunohistochemistry and Western blotting. The main morphological characteristics of injured muscle fibers around MTrPs include gathered circular or elliptical shapes of different sizes in the cross-section and continuous inflated and tapering fibers in the longitudinal section. After intramuscular injection of U0126 (ERK inhibitor), the mechanical pain threshold significantly increased. The reduction in mechanical hyperalgesia was accompanied by reduced ERK protein phosphorylation, myosin light chain kinase (MLCK) protein, p-MLC protein expression, and the cross-sectional area of skeletal muscle cells around MTrPs. An ERK inhibitor contributed to the attenuation of mechanical hyperalgesia in the rat myofascial pain model, and the increase in pain threshold may be related to MLCK downregulation and other related contraction-associated proteins by ERK.