Hematopoietic cell kinase activation in skeletal myocytes contributes to local inflammation and pain sensitization in myofascial trigger points.

Myofascial trigger points (MTrPs) are key pathological features of myofascial pain syndrome (MPS), and local inflammation is a key driver of their initiation and persistence. Hematopoietic cell kinase (HCK) is critical for the regulation of inflammation; however, its role in MTrPs remains unreported. The study was designed to characterize the expression profile, cellular localization and functional significance of HCK in MTrPs. MTrPs tissues were obtained from the trapezius muscles of patients with MPS via needle biopsy for RNA sequencing and phosphorylation antibody microarray analysis to characterize the gene expression profiles and HCK activation. A rat MTrPs model was employed to explore the role of HCK. The HCK inhibitor A419259 was locally injected into MTrPs to evaluate its analgesic effects. Pain-like behaviors were assessed using the Randall-Selitto and nest-building tests. The effects of the HCK inhibitor on local inflammation were evaluated via RT-qPCR. Differentially expressed mRNAs in human MTrPs were predominantly enriched in the inflammation-related pathways. Phosphorylated HCK concentrations were significantly elevated in both human and rat MTrPs model. Immunolocalization demonstrated that phosphorylated HCK was mainly expressed in the skeletal myocytes rather than in the infiltrating immune cells. Local injection of A419259 markedly inhibited cytokine expressions in MTrPs and ameliorated pain-like behaviors (increased mechanical withdrawal threshold, improved nest-building ability, and reduced anxiety-like behaviors) in MTrPs rat models. HCK activation in skeletal myocytes contributes to local inflammation and peripheral sensitization of MTrPs. HCK is a promising therapeutic target for local injection therapy for MPS.