In vivo biological response to extracorporeal shockwave therapy in human tendinopathy

Abstract

Extracorporeal shock wave therapy (ESWT) is a noninvasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session of ESWT was administered to the mid-portion of the Achilles tendon in thirteen healthy individuals (aged 25.7 ± 7.0 years) and patellar or Achilles tendon of six patients with tendinopathies (aged 39.0 ± 14.9 years). Dialysate samples from the surrounding peri-tendon were collected before and immediately after ESWT. Interleukins (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, vascular endothelial growth factor and interferon-γ were quantified using a cytometric bead array while gelatinase activity (MMP-2 and -9) was examined using zymography. There were no statistical differences between the biological tissue response to ESWT in healthy and pathological tendons. IL-1β, IL-2, IL-6 and IL-8 were the cytokines predominantly detected in the tendon dialysate. IL-1β and IL-2 did not change significantly with ESWT. IL-6 and IL-8 concentrations were elevated immediately after ESWT and remained significantly elevated for four hours post-ESWT (p < 0.001). Proforms of MMP-2 and -9 also increased after ESWT (p < 0.003), whereas there were no significant changes in active MMP forms. In addition, the biological response to ESWT treatment could be differentiated between possible responders and non-responders based on a minimum 5-fold increase in any inflammatory marker or MMP from pre-to post-ESWT. Our findings provide novel evidence of the biological mechanisms underpinning ESWT in humans in vivo. They suggest that the mechanical stimulus provided by ESWT might aid tendon remodelling in tendinopathy by promoting the inflammatory and catabolic processes that are associated with removing damaged matrix constituents. The non-response of some individuals may help to explain why ESWT does not improve symptoms in all patients and provides a potential focus for future research.

Utility of Ultrasonography in Assessing the Effectiveness of Extracorporeal Shock Wave Therapy in Insertional Achilles Tendinopathy

“…In animal and in vivo experiments, some studies have reported that ESWT stimulated the ingrowth of neovascularization at the tendon-bone junction and promoted the inflammatory and catabolic processes [15, 16]. Others have demonstrated that ESWT significantly decreased the nonmyelinated sensory fibers and increased tenocyte proliferation, collagen synthesis, glycosaminoglycan (GAG) content, protein synthesis, and transforming growth factor- (TFG-) β 1 [17–19].…”

Radial extracorporeal shockwave therapy for the treatment of finger tenosynovitis (trigger digit)

“…However, the specific biological mechanisms by which it induces therapeutic effects on pathological tendon tissue are not completely elucidated. Evidence from a recent study of human tendons suggested that the mechanical stimulus of ESWT aids tendon remodeling by promoting inflammatory and catabolic processes that are associated with the removal of damaged matrix constituents 42. In vitro studies have further suggested that ESWT increases tendon healing through the stimulation of cell proliferation and motility, neovascularization, and expression of critical differentiation genes 43.…”

Achilles Tendinopathy: Current Concepts about the Basic Science and Clinical Treatments

“…How ESWT works is still poorly understood, but it is known to cause selective dysfunction of sensory unmyelinated nerve fibers, alteration in the dorsal root ganglia, and cavitation in interstitial and extracellular disruption, which could promote the healing response [74]. Recently, an in vivo study found that mechanical stimulus provided by ESWT might aid the initiation of tendon regeneration in tendinopathy by promoting proinflammatory and catabolic processes that are associated with removing damaged matrix constituents [75]. In recent research, series randomized placebo-controlled trials have confirmed the high evidence of efficacy of ESWT in chronic Achilles tendinopathy [74].…”