BACKGROUND

Myofascial trigger points (MTrPs) are a primary cause of myofascial pain syndrome. Current studies suggest that MTrPs consist of persistent sarcomere contraction and an inflammatory microenvironment. IL-17 has been implicated in the progression of inflammation. However, its expression of IL-17 in MTrPs and the underlying mechanisms remain unclear.

PURPOSE

This study aimed to characterise IL-17 signalling and elucidate the associated molecular mechanisms in the context of MTrPs, and evaluate the therapeutic effects of isoliquiritigenin (ISL) on MTrPs.

METHODS

We examined IL-17A signalling expression using immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blot analysis in MTrPs rat. Haematoxylin and eosin staining and transmission electron microscopy were used to assess muscle fibre and sarcomere morphology. The Randall-Selitto test was employed to evaluate pain-like behaviours in rats. Dihydroethidium staining, JC-1 assay, and ATP quantification were used to assess inflammation-associated mitochondrial function in vitro and in vivo. Additionally, molecular docking, cellular thermal shift, and drug affinity responsive target stability assays were conducted to examine the interaction between ISL and the IL-17 receptor subunit A (IL-17RA) protein.

RESULTS

IL-17A and IL-17RA were significantly expressed in rats with MTrPs. These rats exhibited elevated oxidative stress level and reduced ATP production. Studies on IL-17A stimulated myotubes and gastrocnemius muscle indicated that IL-17RA signalling contributes to inflammation, abnormal sarcomere contraction and mitochondrial dysfunction in MTrPs. Lentivirus-mediated IL-17RA knockdown in the rats further confirmed these findings. Inhibition of the mitogen-activated protein kinase p38 and subsequent rescue experiments highlighted the critical role of IL-17RA/Act1/p38 signalling. Notably, molecular docking and validation experiments revealed that ISL binds to and inhibits IL-17RA, thereby disrupting IL-17RA/Act1/p38 signalling, and ultimately suppressing the maintenance of MTrPs.

CONCLUSION

This study demonstrates that ISL ameliorates sarcomere contraction and inflammatory responses by inhibiting the IL-17RA/Act1/p38 signalling pathway in rats with MTrPs, highlighting its potential as a novel therapeutic strategy for myofascial pain syndrome (MPS).