Extracorporeal shock wave therapy
Extracorporeal shock wave therapy (ESWT) is a well investigated and widely used treatment modality for a number of musculoskeletal disorders. A limitation of ESWT is its potential painfulness at higher, clinically relevant energy flux density (EFD), which may limit its applicability and, thus, effectiveness. Various studies in the literature demonstrated that neither application of a higher number of extracorporeal shock waves with lower EFD nor use of local anesthesia may solve this problem. Based on the results of several other studies in the literature it is hypothesized here that in patients suffering from musculoskeletal disorders that can be treated with ESWT, pretreatment with a pulsed, high power laser with a wavelength of 904 or 905 nanometers (hereafter: “laser pretreatment”) does not only allow to apply higher EFDs in subsequent ESWT but actually results in faster and/or better treatment outcome than
ESWT without laser pretreatment. Accordingly, it is hypothesized here that combining ESWT with laser pretreatment leads to synergistic effects and, thus, is superior to either treatment modality alone. Confirming this hypothesis in preclinical and clinical research may raise significance and increase the use of ESWT in physical and rehabilitation medicine, with immediate benefit for patients.
Significance of extracorporeal shock wave therapy
Extracorporeal shock wave therapy (ESWT) is a well investigated and widely used non-pharmacological, non-surgical treatment modality for a number of musculoskeletal disorders including rotator cuff pathology with or without calcification, tennis elbow, knee osteoarthritis, Achilles tendinopathy, plantar fasciopathy, myofascial trigger points and fracture nonunions. The Physiotherapy Evidence Database PEDro (with over 48.000 randomized controlled trials (RCTs), systematic reviews and clinical practice guidelines currently the largest independent database in the field of physical and rehabilitation medicine) has listed more than 150 RCTs on ESWT since its inception until today. For certain conditions, RCTs on ESWT are the predominant type of RCT listed in PEDro and/or obtained the highest PEDro quality scores among all investigated treatment modalities.
A typical treatment protocol of ESWT comprises three treatment sessions at 1-week intervals, with 2000 extracorporeal shock waves (ESWs) per treatment session applied at a certain energy flux density (EFD) (explained in the next paragraph).
Basic physical principles of extracorporeal shock wave
Extracorporeal shock waves are single acoustic impulses with an initial high positive peak pressure (P+) between 10 and 100 Megapascal (MPa) reached in less than one microsecond (µs) (note that 10 MPa (100 Bar) is the pressure in a water depth of 1009 meters, and 100 MPa (1000 Bar) is the pressure in a water depth of 10.187 meters). The positive pressure is followed by a low tensile pressure (with negative peak pressure (P-) up to -20 MPa ) lasting for a few µs . For all that is known, both the positive (associated with stress) and negative (associated with cavitation) components of ESWs are responsible for therapeutic bioeffects . The life cycle of an extracorporeal shock wave is approximately 5-20 µs.
A key characteristic of ESWs is their energy flux density (EFD), which is calculated as the integral of pressure over time. The EDF related to the positive pressure is EFD+, the EFD related to the negative pressure is EFD-, and the total EFD is the sum of EFD+ and EFD- Radial ESWs differ from focused ESWs in the penetration depth into the tissue, a number of physical characteristics and the technology for generating them. Radial ESWs are not real shock waves in the strict physical sense. Focused ESWs may or may not be real shock waves in the strict physical sense, depending on their pressure characteristics and the way they are generated. Compared to measurements performed in water, penetration of focused ESWs through biological tissue was demonstrated to cause a reduction in both P+ and P- as well as an increased rise time (i.e., the time between 10% of P+ and 90% of P+). In consequence, one should keep in mind that those focused ESWs that are real shock waves in the strict physical sense when measured in water may lose this characteristic in biological tissue. On the other hand, the rise time of the applied ESWs is possibly rather insignificant for the effectiveness of ESWT.
Mode of action of extracorporeal shock waves on musculoskeletal tissue
The release of substance P (one of the body’s neurotransmitter of pain and heat), calcitonin gene-related peptide and other inflammation mediators from afferent nerve fibers is generally referred to as neurogenic inflammation. The latter was demonstrated being involved in the pathogenesis of tendinopathies such as tennis elbow and Achilles tendinopathy. A key working mechanism of ESWs on musculoskeletal tissue is overstimulation of substance P nerve fibers, which depletes presynaptic substance P. As a result, the nerves are apparently unable to report pain for an extended period of time, which leads to reduction in sensation of pain and blockade of neurogenic inflammation.
Furthermore, ESWs can lead in the treated tissue to a stronger expression of growth factors such as bone morphogenetic proteins (BMPs), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) as well as to activation of cells that are involved in tissue regeneration.
Current limitations of extracorporeal shock wave therapy
Several studies (RCTs, meta-analyses and a recent systematic review) demonstrated superiority of ESWT performed at higher EFD compared with ESWT performed at lower EFD. Unfortunately, due to its action on substance P nerve fibers ESWT may become very painful at higher, clinically relevant EFD, which may limit its applicability and, thus, effectiveness.
A key study on focused extracorporeal shock wave therapy (fESWT) for chronic calcifying tendonitis of the shoulder demonstrated that two treatment sessions with 6000 focused ESWs each with EFD+ = 0.08 mJ/mm2 resulted in worse clinical outcome than two treatment sessions with 1500 focused ESWs each with EFD+ = 0.32 mJ/mm2 (in both cases the cumulative EFD+ was 0.96 J/mm2). In line with these results, a very recent study on radial extracorporeal shock wave therapy (rESWT) for knee osteoarthritis demonstrated that four treatment sessions with 4000 radial ESWs each with EFD+ = 0.12 mJ/mm2 resulted in worse clinical outcome than four treatment sessions with 2000 radial ESWs each with EFD+ = 0.24 mJ/mm2 (in both cases the cumulative EFD+ was 1.92 J/mm2). Accordingly, applying a higher number of ESWs with lower EFD does not solve the problem that ESWT may become very painful at higher EFD, potentially limiting its applicability and, thus, effectiveness.
In several recent studies this problem was circumvented by applying the individual, maximum EFD a patient could tolerate [35-37]. However, this may result in increased interindividual differences in the amount of shock wave energy applied in the same study, with potential impact on interindividual differences in treatment success.
Other authors have approached this problem by applying ESWT with local anesthesia. However, it turned out that local anesthesia may block the action of ESWs on substance P nerve fibers, and repetitive ESWT without local anesthesia was demonstrated being more effective than repetitive ESWT with local anesthesia in the treatment of chronic plantar fasciopathy. In summary, the problem that the desire for higher EFDs in ESWT is opposed by the painfulness of the treatment has remained unsolved.