MolecularMechanismsUnderlyingthePain-RelievingEffectsofExtracorporealShockWaveTherapy:AFocusonFasciaNociceptors

Myofascial pain syndrome (MPS) is one of the most common and disabling musculoskeletal conditions, affecting a large proportion of patients with chronic pain. It is characterized by the presence of hyperirritable nodules called myofascial trigger points (MTrPs) within skeletal muscle fibers or muscle fascia. Despite the prevalence of MPS, many conventional treatments—including dry needling, ultrasound, stretching, massage, and taping—show limited effectiveness, with pain often persisting or worsening over time. In recent years, extracorporeal shock wave therapy (ESWT) has emerged as a promising non-invasive alternative for managing various musculoskeletal disorders, including MPS.

While ESWT was originally developed in the 1980s for urinary stone treatment (lithotripsy), its applications have expanded dramatically to include bone and soft-tissue pathologies. A particularly intriguing aspect of ESWT is its ability to produce long-lasting pain relief, sometimes persisting for months to years after just a couple of treatment sessions. However, the precise molecular mechanisms behind this analgesic effect remain poorly understood. This review addresses the critical need to understand how ESWT alleviates pain, with special attention to the role of fascial sensory innervation and nociceptors, which are increasingly recognized as major contributors to musculoskeletal pain generation.

The authors conducted a comprehensive narrative review of existing literature to explore the molecular mechanisms underlying ESWT-induced pain relief, with a specific focus on fascia nociceptors. They examined multiple lines of evidence including: (1) the technical and biological characteristics of ESWT, including differences between focused (fESWT) and radial (rESWT) shock wave delivery systems; (2) the anatomy and sensory innervation of the human fascial system, particularly the deep fascia; (3) clinical studies demonstrating ESWT efficacy in various musculoskeletal conditions; (4) in vivo animal studies investigating nerve fiber changes following shock wave application; and (5) proposed molecular mechanisms including neuropeptide modulation, selective nerve fiber degeneration, and alterations in pain neurotransmission. The review synthesizes findings from histological studies, electrophysiological investigations, immunohistochemical analyses, and randomized controlled trials to build a mechanistic understanding of ESWT analgesia.

The review identified several key mechanisms by which ESWT may produce pain relief. First, multiple animal studies demonstrated that ESWT causes selective degeneration of small sensory unmyelinated nerve fibers (C-fibers). One study in rabbits found a "substantial reduction of unmyelinated nerve fibers" within the femoral nerve six weeks after ESWT application. Second, ESWT reduces pain-related neuropeptides, particularly substance P (SP) and calcitonin gene-related peptide (CGRP).

Animal studies showed decreased SP release from periosteum, reduced CGRP-immunoreactive sensory nerve fibers, and diminished percentages of CGRP-positive dorsal root ganglion neurons following shock wave treatment. Third, repetitive ESWT application appears to amplify denervation effects and prolong analgesia. One study found that a second shock wave application accentuated inflammatory changes that prevented local reinnervation. Fourth, clinical studies in humans demonstrated significant pain reduction across multiple conditions: in chronic plantar fasciitis, VAS scores decreased from 77 points to 19 points at 6 months; in myofascial pain syndrome of the upper trapezius, pressure pain threshold increased from 40.4 N to 61.2 N; and in myofascial trigger points, 95% of patients showed significant VAS score decrease from 3.6 to 1.7 after 3 months.

The review also highlighted that fascial tissue contains a greater density of sensory nerve fibers with nociceptive capability compared to adjacent muscle tissue—specifically, CGRP-positive fibers in the thoracolumbar fascia of mice showed density three times higher than in back muscles. Pathological alterations in fascia, including inflammation and changes in hyaluronic acid, can activate fascial nociceptors and sensitize dorsal horn neurons, contributing to chronic pain states.

This review suggests that ESWT's pain-relieving effects in myofascial pain syndrome likely stem from its targeted actions on the rich sensory innervation of fascial tissues. Unlike muscles, fascia contains abundant nociceptive free nerve endings that appear particularly susceptible to shock wave-induced changes. For patients with chronic myofascial pain that has not responded to conventional treatments, ESWT offers a non-invasive alternative with potential for long-lasting benefit. The selective destruction of unmyelinated pain fibers, combined with reduced neuropeptide signaling and prevention of reinnervation, provides a mechanistic rationale for the durable analgesia observed clinically.

For clinicians, this understanding supports the use of ESWT as part of a multimodal approach to MPS management, particularly for patients with fascial-dominant pain presentations. However, the authors note that clear evidence specifically demonstrating ESWT effects on fascial nociceptors is still lacking, and future research should directly investigate these interactions. The dose-dependent nature of ESWT effects and optimal treatment protocols remain to be fully established. Additionally, understanding whether certain subtypes of MPS patients (those with more prominent fascial involvement) respond better to ESWT could help personalize treatment selection.