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13 Articles in Volume 12, Issue #11
“Doc” Holliday: A Story of Tuberculosis, Pain, and Self-medication in the Wild West
"Doc's" Woman: Doc Holliday's Wife
Activation of Latent Lyme Disease Following Epidural Steroid Injection: Case Challenge
An Overview of Complex Regional Pain Syndrome and its Management
Extracorporeal Shock Wave Therapy: Applications in Tendon-related Injuries
Mission Impossible—Developing a Program to Help Chronic Pain Patients
New Ideas for Helping Difficult Pain Patients
Postoperative Pain Relief After Knee and Hip Replacement: A Review
Using Dynamic MRI to Diagnose Neck Pain: The Importance of Positional Cervical Cord Compression (PC3)
December 2012 Pain Research Updates
Best Practices For High-dose Opioid Prescribing
Does Sulindac Affect Renal Function Less Than Other NSAIDs?
The Bewildering Terminology of Genetic Testing

Extracorporeal Shock Wave Therapy: Applications in Tendon-related Injuries

Part two of a three-part series examines the role of extracorporeal shock wave therapy in the management of difficult to treat tendonosis and enthesopathies.

Most pain clinicians will agree that there is a certain class of musculoskeletal (MSK) disorders that have historically been very challenging to treat and too often result in patients being labeled as non-genuine in their representation of the problem. A seemingly simple diagnosis—such as tendonitis, bursitis, fasciitis, or epicondylitis—can become chronic without warning, eventually leading to disability and significant lost time from work.

This is part two of a three-part series:  read part one.

This is particularly relevant in the field of occupational medicine or work-related injuries, where both indemnity payments and medical bills for diagnosis and treatments add cost to the care scenario. The ultimate goal of return to work is difficult when clinicians are confronted with a recalcitrant condition that demonstrates resistance to our best medical, surgical, and rehabilitation efforts.

Although we have no way of predicting which cases will go on to become chronic, biological evidence is mounting that what starts as an uncomplicated tendon strain, can steadily morph into a much more complex disorder (tendinosis) with time.1 These difficult MSK cases often reveal that the tendon-bone attachment or enthesis is the focal point of pathological changes.

A Growing Problem
Tendon injuries are ubiquitous in our industrialized society. This is partly due to the repetitive nature of many jobs, and partly to a lack of individual fitness, which encompasses a number of factors including gradual age-related deconditioning. It can be argued that as individuals we need to take better care of our human frames including ongoing maintenance in the form of stress, nutrition, and exercise management versus the “fix it only when it breaks” mentality, which arguably defines much of our current tertiary approach to care.

Whether one agrees with this assessment or not, we should still recognize that primary prevention is predicted to be an important policy pillar of our healthcare system in the United States today. When resources are finite, society must find a way to effectively treat patients without as much reliance on expensive pharmacotherapies, invasive procedures (injections), surgeries, postsurgical rehabilitation, etc. It is clear that patients will play a greater role in determining their ultimate health status. Physicians will need to engage patients with alternative strategies for improving health and fitness including guiding, supporting, and directing patients to make better lifestyle choices in nutrition, activity, stress, leisure, and medication management.2 One of the results might be a society with less dependence on medication and medical tests/procedures and greater affinity for regular exercise and improved nutrition status.

The situation is obviously much more complicated than that, but these might be a few of the changes we notice in the next few years as we divert resources to focus on prevention. We are on the cusp of a medical revolution of sorts, with the advent of regenerative medicine becoming the new model for healing and standard for medical care. It is within the context of this powerful new paradigm that we present part two of this three-part series focusing on myotripsy, or shockwave therapy. At the very core of regenerative medicine is signal transduction occurring at the cellular level, also known as mechanotransduction.3

Cellular Signaling in Mechanical Transduction
Cellular intelligence is an evolutionary process and there is evidence to suggest that our cells have evolved through genetic pressure or the preferential selection of advantageous genetic mutations. Cells with a greater ability to produce, recognize, interpret and respond to signals in the environment would be better prepared to survive. The “signaling” aspect in cellular communication is thought to be both a function of chemical messengers or molecules combined with an underlying electro-magnetic energy acting as the driving force to the system.4 Chemical molecules are made available by one cell and specifically combine with receptor mechanisms on another cell’s surface, and so the transduction process begins.

This relatively new conceptual framework in molecular biology research has medical scientists excited because of the enormous implications behind it. Many of the leading diseases that public health professionals are most concerned with today are the result of a breakdown in any one of these three steps:

  • Cell signaling, or the release of an organic or inorganic chemical molecule (protein, peptide, gas, amino acid, nucleotide, or steroid)
  • Signal recognition, usually occurring at the receiving cell surface via specific receptor binding
  • Internal signaling, where molecules convert the original signal into internal behavior5

This is a very simplified multi-step summary of signal transduction. This background information will become an important segue into how myotripsy, or extracorporeal shock wave therapy (ESWT), can effectively interact with damaged tissue.

The extracellular matrix (ECM) forms the fundamental environment through which all cellular activity can take place since it is the conduit from extra- to intracellular activities. Every cell in the body is immersed in and surrounded by an ECM component that allows cell-to-cell communication along with other vital cell functions such as transport, metabolism, and drug interactions. Figure 1 depicts the ECM of the subdermal region, while Figure 2 depicts the ECM of muscle fibers. The ECM is really the basis for the fascial network that surrounds all cells of the body and provides an inter-connectedness that goes well beyond that described by conventional anatomy books. We now know that functional anatomy has so much more relevance in clinical practice and can provide, not only better insights into disease pathophysiology, but also hints at how to prevent and/or rehabilitate it.

Tendon/Ligament Attachment Sites
Insertional irritations are difficult to treat at best, and can be an exercise in frustration for both patient and practitioner at worst. These osteotendinous and/or osteoligamentous junctures represent a morphologically unique area in the anatomy of soft/bony tissue. This interface between soft tissue and bone can be divided into two primary types—fibrous (F) and fibrocartilaginous (FC)— according to the type of tissue present at the attachment site. The FC enthesis, or attachment site, does not have a periosteum and is referred to as a direct attachment.6 In either case, there is a postulated enthesis organ whose function at or near the enthesis serves a common function of stress dissipation. We will not provide a detailed analysis of the enthesis organ but suffice it to say that this structure is of particular importance to clinicians because it helps explain the patterns of injury and the diffuse nature of symptoms.7

Enthesis organs differ slightly from region to region but what many have in common is that the ligament of tendon attaches to a pit or a small bony protuberance next to the enthesis. In either case, there is contact between tendon/ligament and bone immediately next to the enthesis, which dissipates stress away from the enthesis, but often stimulates the development of a sesamoid
and/or periosteal fibrocartilage. Adding to the complexity of the location of these organs, some enthesis organs are shared as seen with popliteus and the lateral collateral ligament of the knee joint.8 The anatomy literature is replete with examples of multi-enthesis or shared organs such as that of extensor carpi radialis brevis merging imperceptibly with the lateral collateral ligament, which then continues to merge with the annular ligament of the radioulnar joint. As a result, considerable load sharing occurs between structures.

It is further postulated that the enthesis organ acts to provide proprioception to the joint as seen in the Achilles insertional complex, which also includes the fat pad that is interposed between the tendon and bone. This strategic positioning of the fat pad is thought to be so as to not only prevent kinking of the tendon and/or to reduce friction between tendon and bone, but since the pad is infiltrated with nerve endings it is speculated to help monitor changes in the angle between bone and tendon during foot movements.9

Another common feature of enthesis sites is that they are avascular, which reflects the fact that these structures are subjected to compression forces. This avascularity is important because of the implications it has for overall healing. It is not known what regulatory mechanisms are involved in determining the vascularity level of insertion sites, including angiogenic and/or anti-angiogenic factors involved. From a clinical standpoint, the avascular nature of enthesis sites makes any treatment difficult to act as a catalyst for healing. Tendons/ligaments also have notoriously slow regeneration rates due to low proliferation rates during in vivo experimentation. In combination then, the tendon/ligament’s poor regenerative potential added to the poor vascularization of the insertion site (enthesis) make for a challenging healing scenario in chronic tendinopathy and/or enthesopathy.

Figure 1. Illustration of the subdermal extracellular matrix interposed between dermal layers.

Figure 2. Illustration of a similar idea as seen in Figure 1. above

Functions of Enthesis in Tendon/Ligament
The two primary functions of enthesis sites are to anchor soft tissue (tendon/ligament) to bone, and secondly to dissipate stress. An exploration of the attachment anatomy of the enthesis organ is a fascinating endeavor and one worth exploring. What becomes very clear almost immediately is that these sites don’t simply attach to one point in a single axis. The attachment sites are characterized by a flaring or fanning at the insertion, thus maximizing the attachment area, making the area more secure for force transmission. The other aspect of attachment is that there is a blending of the attachment sites to other distinct tissues, forming what some have called myofascial slings. This concept is consistent with what Myers described in 2001 as myofascial continuity between muscle groups once thought to be distinct, but in fact, acting in concert to produce mechanically linked lines of force transmission.10

In clinical practice, we see enthesopathy in various formats including rheumatoid arthritis, spondyloarthropathy, calcium pyrophosphate deposition disease, and diffuse idiopathic skeletal hyperostosis. There is some controversy regarding whether enthesopathy is an inflammatory or degenerative condition. Much of the evidence seems to point to the histological findings, which are in abundance and support these conditions as being more degenerative than inflammatory, but it appears both elements coexist in varying degrees. Tendons show thinning, collagen fiber disruption, micro-tearing, and increases in vascularity, granulation tissue, and proteoglycan content in the ECM.11 Other changes such as tenocyte degeneration, lipid accumulation, and calcium deposits have been seen as early as age 15 in tendons of the Achilles, quadriceps, and patella.12

Myotripsy in Chronic Tendinopathy
Myotripsy is the next generation ESWT, and uses low energy levels in comparison to the first-generation devices that utilized a higher energy output and required local anesthesia. We now know that local anesthesia interferes with mechanotransduction and the essential cell signaling process.13 Figure 3 depicts a patient treatment using myotripsy for enthesopathy of the shoulder supraspinatus insertion. The primary mode of action for myotripsy lies in the physical composition of the output wave, which is a radial acoustic pulse or shockwave with mechanical properties. The theoretical construct by which mechanical forces initiate the signaling cascade transforming mechanical into chemical energy is defined by mechanotransduction. There are two primary effects that are desired when using myotripsy to target tissue: stimulation of production of cytokines, growth factors, neurotransmitters, heat shock proteins, and reactive oxygen nitrogen species for new tissue generation; and the gene expression of the cell should be affected at the molecular level.14

On a larger scale, there are changes at the macroscopic level involving tendons undergoing pathological conversion that involve both inflammation and degeneration. The intra-tendinous regions demonstrate focal tendon tissue loss and a concomitant loss of color from glistening white to a darker gray appearance. The texture of the tendon changes and becomes thicker, rougher, and nodular at times. Symptomatic tendon samples have been found to be hypoxic, mucoid, and containing fatty degeneration. These changes were found in 90% of tendons tested.15 Other common histological changes found in painful tendons included calcifications, neovascularization, and a general loss of collagen tissue.15

Figure 3. Treatment of a patient using myotripsy

Myotripsy has shown impressive results in treating these extremely difficult and costly disorders of the enthesis. In a randomized controlled clinical trial, Wang et al studied 50 patients with chronic patellar tendinopathy.16 In the study group, 27 patients (30 knees) were treated with 1,500 pulses of ESWT at 0.18 mJ/mm2 of energy at a single session. The control group (23 patients) was treated with standard physical therapy, exercises, non-steroidal anti-inflammatory drugs, and a knee strap. Outcome measures included a standardized tool to measure function, ultrasonography examination, and self-report pain scores at 1, 3, 6, and 12 months after treatment. At 2- and 3-year follow up, the results clearly favored the treatment group, especially when comparing pathology recurrence rates and US findings suggestive of positive morphological changes in the shockwave group. Satisfactory results were observed in 90% of the study group versus 50% of the control group (P<.001). Recurrence of symptoms occurred in 13% of the study group and 50% of the control group (P=.014). The shockwave-treated tendons showed a reduction in tendon thickness. The authors concluded that the shockwave treatment seemed to be more effective and safer overall than the control group receiving standard care.16

In the treatment of other commonly afflicted areas of the body, including the Achilles tendon of the foot,17 the rotator cuff of the shoulder,18 and the epicondylar region of the elbow,19 similar positive study results have been reported from independent groups studying the effects of shockwave myotripsy on chronic tendinopathic disorders.

Conclusion
The application of shockwave myotripsy in the treatment of enthesopathic and/or tendinopathic lesions is becoming more popular. The preponderance of the research supports a significantly improved clinical outcome when myotripsy is part of the treatment plan. Whether used as a standalone therapy, or integrated into a comprehensive rehabilitation care plan, shockwave therapy is proving to be a valuable addition in the treatment of chronic problems affecting collagen tissue at musculotendinous attachment sites. Within the context of a rapidly emerging paradigm of mechanobiology, clinicians can now better appreciate the role of the collagen-based fascial system that weaves through our musculoskeletal system forming anatomical linkages never before appreciated nor understood. We appear to be on the brink of a true paradigm shift in our understanding of how external forces effect and control cellular behavior. The acoustic energy emitted by shockwaves appears to be effective in assisting tissue regeneration and improving tendon function. More research using shockwaves is undoubtedly forthcoming in areas such as spinal cord research and as a complimentary treatment to such novel applications as stem cell research and platelet rich plasma therapy.

Last updated on: December 20, 2012
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