Platelet-derived Growth Factor Receptor-α Induces Contraction Knots and Inflammatory Pain-like Behavior in a Rat Model of Myofascial Trigger Points

• Published in: Anesthesiology (Philadelphia) Vol. 141; no. 5; pp. 929 - 945
• Main Authors: Liu, Yu, Jin, Feihong, Zhou, Lingwei, Li, Xuan, Li, Xiaoyue, Chen, Qinghe, Yang, Shaozhong, Sun, Jintang, Qi, Feng
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01-11-2024
• Subjects: Animals; Disease Models, Animal; Female; Humans; Inflammation - metabolism; Inflammation - pathology; Janus Kinase 2 - metabolism; Male; Muscle Contraction - physiology; Myofascial Pain Syndromes - metabolism; Myofascial Pain Syndromes - physiopathology; Pain Medicine: Basic Science; Rats; Rats, Sprague-Dawley; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Signal Transduction - physiology; STAT3 Transcription Factor - metabolism
• ISSN: 0003-3022; 1528-1175; 1528-1175
• DOI: 10.1097/ALN.0000000000005167

Myofascial trigger points (MTrPs) are the primary etiological characteristics of chronic myofascial pain syndrome. Receptor tyrosine kinases (RTKs) are associated with signal transduction in the central mechanisms of chronic pain, but the role of RTKs in the peripheral mechanisms of MTrPs remains unclear. The current study aimed to identify RTKs expression in MTrPs and elucidate the molecular mechanisms through which platelet-derived growth factor receptor-α (PDGFR-α) induces contraction knots and inflammatory pain-like behavior in a rat model of myofascial trigger points.
MTrPs tissue samples were obtained from the trapezius muscles of patients with myofascial pain syndrome through needle biopsy, and PDGFR-α activation was analyzed by microarray, enzyme-linked immunosorbent assay, and histological staining. Sprague-Dawley rats (male and female) were used to investigate PDGFR-α signaling, assessing pain-like behaviors with Randall-Selitto and nest-building tests. Muscle fiber and sarcomere morphologies were observed using histology and electron microscopy. The PDGFR-α binding protein was identified by coimmunoprecipitation, liquid chromatograph mass spectrometer, and molecular docking. PDGFR-α-related protein or gene levels, muscle contraction, and inflammatory markers were determined by Western blot and reverse-transcription quantitative polymerase chain reaction.
PDGFR-α phosphorylation levels were elevated in the MTrPs tissues of individuals with trapezius muscle pain and were positively correlated with pain intensity. In rats, PDGFR-α activation caused pain-like behaviors and muscle contraction via the Janus kinase 2/signal transducer and activator of transcription-3 (JAK2/STAT3) pathway. JAK2/STAT3 inhibitors reversed the pain-like behaviors and muscle contraction induced by PDGFR-α activation. Collagen type I α 1 (COL1A1) binds to PDGFR-α and promotes its phosphorylation, which contributed to pain-like behaviors and muscle contraction.
COL1A1-induced phosphorylation of PDGFR-α and the subsequent activation of the JAK2/STAT3 pathway may induce dysfunctional muscle contraction and increased nociception at MTrPs.