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

Abstract

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.

Magnolin Inhibits Paclitaxel-Induced Cold Allodynia and ERK1/2 Activation in Mice

“…ERK1 and ERK2 (ERK1/2) belong to an evolutionarily conserved group of serine/threonine protein kinases, and they play important roles in the change of the nervous system in various diseases. Previous studies have reported that phosphorylation of ERK (pERK) is increased in the sensory nervous system in neuropathic pain conditions, resulting in the manifestation of allodynia and hyperalgesia symptoms [ 5 , 6 , 7 , 8 , 9 ]. It has been also reported that inhibiting the ERK is effective in relieving pain in animal models of this neuropathic pain, suggesting the ERK could be an important therapeutic target for the treatment of neuropathic pain [ 10 ].…”

Dexmedetomidine inhibits abnormal muscle hypertrophy of myofascial trigger points via TNF-α/ NF-κB signaling pathway in rats

“…In our previous studies, we used disposable biopsy instrument (SuperCore™, Argon Medical Devices, Inc.) for MTrPs muscle tissue and performed morphological observations. Hematoxylin and eosin (HE) staining revealed abnormal hypertrophy of skeletal muscle fiber at the MTrPs( Zhang et al, 2020b ; Jin et al, 2020 ; Jin et al, 2020 ; Zhu et al, 2020 ). The muscle fibers in the MTrPs showed annular or elliptical muscle fibers of different sizes in cross-sectional views ( Jin et al, 2020 ).…”

“…Many previous studies proved that the histological hallmark of MTrPs is the abnormal hypertrophy of local skeletal muscle ( Huang et al, 2015 ; Zhang et al, 2020b ; Jin et al, 2020 ; Zhu et al, 2020 ). However, whether MEF2C is involved in MTrPs remain unknown.…”