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节和炎症性疼痛样行为。

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

机构信息

Department of Anesthesiology, and Research Center for Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

出版信息

Anesthesiology. 2024 Nov 1;141(5):929-945. doi: 10.1097/ALN.0000000000005167.

DOI:10.1097/ALN.0000000000005167

PMID:39058323

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11463032/

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.

摘要

背景

肌筋膜触发点（MTrPs）是慢性肌筋膜疼痛综合征的主要病因特征。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 的外周机制中的作用尚不清楚。本研究旨在确定 MTrPs 中的 RTKs 表达，并阐明血小板衍生生长因子受体-α（PDGFR-α）在肌筋膜触发点大鼠模型中诱导收缩结和炎症性疼痛样行为的分子机制。

方法

通过针活检从患有肌筋膜疼痛综合征的患者的斜方肌中获取 MTrPs 组织样本，并通过微阵列、酶联免疫吸附试验和组织学染色分析 PDGFR-α 激活。使用 Sprague-Dawley 大鼠（雄性和雌性）研究 PDGFR-α 信号转导，使用 Randall-Selitto 和筑巢试验评估疼痛样行为。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、液相色谱-质谱联用和分子对接鉴定 PDGFR-α 结合蛋白。通过 Western blot 和逆转录定量聚合酶链反应测定 PDGFR-α 相关蛋白或基因水平、肌肉收缩和炎症标志物。

结果

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。在大鼠中，PDGFR-α 激活通过 Janus 激酶 2/信号转导和转录激活因子 3（JAK2/STAT3）通路引起疼痛样行为和肌肉收缩。JAK2/STAT3 抑制剂逆转了 PDGFR-α 激活引起的疼痛样行为和肌肉收缩。胶原 I 型α 1（COL1A1）与 PDGFR-α 结合并促进其磷酸化，导致疼痛样行为和肌肉收缩。