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

IF 9.1 1区医学 Q1 ANESTHESIOLOGY

Anesthesiology Pub Date : 2024-11-01 DOI:10.1097/ALN.0000000000005167

Yu Liu, Feihong Jin, Lingwei Zhou, Xuan Li, Xiaoyue Li, Qinghe Chen, Shaozhong Yang, Jintang Sun, Feng Qi

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Editor’s perspective:

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血小板衍生生长因子受体-α在大鼠肌筋膜触发点模型中诱导收缩结和炎性疼痛样行为。

背景：肌筋膜触发点（MTrPs）是慢性肌筋膜疼痛综合征（MPS）的主要病因特征。受体酪氨酸激酶（RTKs）与慢性疼痛中枢机制中的信号转导有关，但RTKs在MTrPs外周机制中的作用仍不清楚。本研究旨在确定 RTKs 在 MTrPs 中的表达，并阐明血小板衍生生长因子受体-α（PDGFR-α）在大鼠肌筋膜触发点模型中诱导收缩结和炎性疼痛样行为的分子机制：通过针刺活检从 MPS 患者的斜方肌获取 MTrPs 组织样本，并通过芯片、酶联免疫吸附试验（ELISA）和组织学染色分析 PDGFR-α 的激活情况。斯普拉格-道利（SD）大鼠（雄性/雌性）被用来研究 PDGFR-α 信号传导，通过兰德尔-塞利托（Randall-Selitto）和筑巢试验来评估类疼痛行为。使用组织学和电子显微镜观察肌肉纤维和肌节形态。通过共免疫沉淀（Co-IP）、液相色谱质谱（LC-MS）和分子对接鉴定了 PDGFR-α 结合蛋白。通过 Western 印迹和反转录定量聚合酶链反应（RT-qPCR）测定了 PDGFR-α 相关蛋白或基因水平、肌肉收缩和炎症标志物：结果：在斜方肌疼痛患者的 MTrPs 组织中，PDGFR-α 磷酸化水平升高，且与疼痛强度呈正相关。在大鼠体内，PDGFR-α的激活通过破伤风激酶2/信号转导和转录激活因子-3（JAK2/STAT3）途径引起疼痛样行为和肌肉收缩。JAK2/STAT3抑制剂可逆转PDGFR-α活化诱导的类疼痛行为和肌肉收缩。Ⅰ型胶原α1（COL1A1）与PDGFR-α结合并促进其磷酸化，从而导致类疼痛行为和肌肉收缩：结论：COL1A1诱导的PDGFR-α磷酸化和随后的JAK2/STAT3通路激活可能会导致肌肉收缩功能障碍和MTrPs处痛觉增强。

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来源期刊

Anesthesiology 医学-麻醉学

CiteScore

10.40

自引率

5.70%

发文量

542

审稿时长

3-6 weeks

期刊介绍： With its establishment in 1940, Anesthesiology has emerged as a prominent leader in the field of anesthesiology, encompassing perioperative, critical care, and pain medicine. As the esteemed journal of the American Society of Anesthesiologists, Anesthesiology operates independently with full editorial freedom. Its distinguished Editorial Board, comprising renowned professionals from across the globe, drives the advancement of the specialty by presenting innovative research through immediate open access to select articles and granting free access to all published articles after a six-month period. Furthermore, Anesthesiology actively promotes groundbreaking studies through an influential press release program. The journal's unwavering commitment lies in the dissemination of exemplary work that enhances clinical practice and revolutionizes the practice of medicine within our discipline.