Molecular Pain · Published 2026-05-13 · DOI 10.1177/17448069261453185
Carl PC Chen, Areerat Suputtitada
Background: Musculoskeletal disorders are increasingly recognized as conditions involving extracellular matrix dysregulation, characterized by fibrosis, calcification, fascial adhesions, and altered nociceptor signaling. These features highlight the role of mechanobiology in pain generation and modulation. Ultrasound-guided hydrodissection has emerged as an intervention capable of perturbing the extracellular microenvironment, with potential downstream effects on nociceptive pathways. Methods: A structured literature search was conducted across PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library (January 2000–March 2026) to identify clinical and mechanistic studies investigating ultrasound-guided hydrodissection, mechanical needling, and sterile water injection. Eligible studies were synthesized qualitatively. Results: Thirty studies were included, encompassing randomized trials, observational studies, and mechanistic investigations across multiple pain conditions. Evidence suggests that mechanical and osmotic perturbation of the extracellular matrix may disrupt fibrotic architecture, facilitate fascial plane separation, and modify the local biochemical microenvironment. Hypotonic sterile water has been associated with activation of mechanosensitive and osmosensitive ion channels, including TRPV1, PIEZO1/2, and ASIC, leading to calcium influx–mediated modulation of neuronal excitability. These processes may contribute to peripheral and central nociceptive modulation through integrated mechanobiological and microvascular mechanisms. Conclusions: Ultrasound-guided mechanical needling with sterile water hydrodissection represents a mechanobiological approach to modulating nociceptive signaling through extracellular matrix perturbation and ion channel activation. This framework provides a translational basis for targeting structural and microenvironmental contributors to pain.
Abstract from DOAJ. Public domain (CC0 1.0).
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Chen, C., Suputtitada, A. (2026). Mechanical needling and sterile water hydrodissection modulate nociception via extracellular matrix perturbation and ion channels. Molecular Pain. https://doi.org/10.1177/17448069261453185