Fig. 8.1
Tendon structure (need to make our own illustration)
There is often a poor correlation between clinical symptoms of tendonopathies and objective evidence of tissue disruption. It is thought that a tendon’s relatively avascular nature limits its capacity for healing. The tensile load imposed on tendons, especially in gliding zones around bony prominences, may induce transient ischemia, creating areas of tissue weakness, loss of cell viability, and even macro-structure disruption (rupture), due to poor perfusion [5]. Histological appearance of a normal tendon differs from a tendon with overuse-type tendinopathy injury/tendinosis though the exact pathological process has yet to be fully elucidated [6].
Tendinopathy seems to be the response to overuse injury resulting in a pathologic cascade of changes in the normal tendon repair process and creating a pathological cycle of degeneration and attempted failed regeneration. Microscopic examination of tissue from painful tendons reveals variable features, such as collagen disarray and fiber disorganization, increased proteoglycans and water, increased number of cells (myofibroblasts and fibroblasts), more chondroid appearance of tenocytes, and the presence of neovascularization [7]. However, there is an absence of inflammatory cells, indicating an insufficient repair process that leads to tendon degeneration. Macroscopic changes include tendon thickening, loss of mechanical properties, and pain [8, 9]. However, imaging studies (i.e., ultrasound, magnetic resonance imaging) reveal that these changes can exist in non-painful tendons and may be an incidental finding. Therefore, tendinopathy must require clinical symptoms and cannot be diagnosed by imaging [10].
Although overuse and overloading are commonly accepted as the cause of tendinopathy, there are a number of other intrinsic and extrinsic factors that may contribute to its development. Intrinsic factors include age, nutrition, vascular perfusion, obesity, adiposity, poor biomechanics, and anatomical variants, which include limb malalignments, bony impingement, leg length discrepancy, joint laxity, muscle weakness/imbalance, systemic disease, and possibly gender [11, 12]. Extrinsic factors include occupation, sport, physical load (repetitive or abnormal/unusual loading), training errors, such as poor technique, fast progression, high intensity, or fatigue, shoes and equipment, environmental conditions, including temperature, and running surface [13].
Common Tendinopathies
The types of overuse injury depend on several factors, including age and activity [14]. For instance, in the pediatric and adolescent population, tendons and ligaments are stronger than the epiphyseal plate, and are thus more prone to injury at the epiphyseal plate rather than the tendon or ligament. When tendon injuries do occur in children, the insertion site of the tendon at the apophyses is more likely injured than the main body of the tendon [15, 16]. In contrast, in the adult population, most tendinopathies refer to intra-tendinous condition. Older patients or adult athletes presenting to musculoskeletal clinics are usually diagnosed with traditional overuse injuries, including rotator cuff injures (18%), Achilles tendon (20%), and medial and lateral epicondylitis, which occur from sport or work-related activities [17]. Common tendinopathies in the upper extremity include rotator cuff tendinopathy, bicipital tendinopathy, and medial and lateral epicondylitis. Common tendinopathies in the lower extremity include hamstring tendinopathy, patellar tendinopathy/jumper’s knee, Achilles tendinopathy, and peroneal tendinopathy [18].
Symptoms
Tendinopathy is the clinical syndrome of tendon pain and dysfunction, usually due to overuse. Symptoms include localized pain with loading, tenderness to palpation, and impaired function. Frequently, tendon pain is characterized by a transient on/off nature consistently linked to loading. Pain is preceded by excessive energy storage and release in the tendon. Therefore, the tendon is rarely painful at rest or during low-load activities. For example, a patient with patellar tendinopathy usually has pain with jumping, but not cycling because of the different demands of the musculotendinous unit. Another characteristic pain pattern of tendinopathy is that the tendon “warms up” and becomes less painful over the course of activity, with variable times of exquisite tendon pain after exercise [19].
Functional Limitations
Chronic tendon pain itself can adversely affect quality of life because of the patient’s inability to participate in exercise, athletic activities, occupation-related activities, or ADLs. However, tendinopathy is also associated with alterations in biomechanics and may affect motor control, movement variability, and strength due to disuse or guarding. Less variable motor patterns create a system that is less adaptive to changes in the environment and increases the likelihood of injury or re-injury [20].
Treatment
Optimal treatment of tendinopathy is debated, though nonoperative management is still the mainstay. Initial treatment includes avoidance of aggravating factors, relative rest, ice, stretching, and analgesic medications. Broadly, conservative management involves physical therapy including modalities, medications, and injections [21].
Conservative Treatments
Rehabilitation management includes physical therapy and physical modalities. Eccentric strengthening is one of the mainstays in the treatment of tendinopathy and involves the application of load and muscle exertion to a lengthening muscle, thought to stimulate tissue remodeling and normalization of tendon structure. Eccentric exercises should be done under the guidance of a trained physical therapist, as overloading the musculotendinous junction can lead to further injury. A systematic review by Kingma et al. found a mean pain reduction of 60% in patients with chronic Achilles tendinopathy who completed eccentric training compared to 33% in control groups (traditional concentric strengthening programs) [22]. Other studies also showed eccentric training was more effective than traditional concentric training for treating Achilles and patellar tendinopathies [23–26].
Physical modalities include sound-assisted soft tissue massage/friction massage, cryotherapy, low-level laser therapy, ultrasound therapy, ionotophoresis/phonophoresis, and extracorporeal shock-wave therapy [21]. Sound-assisted soft tissue massage (SASTM) , augmented soft tissue mobilization (ASTM) , or friction massage involve the application of friction-directed force onto a tendon or ligament to promote or induce physiological and structural tissue changes. This is thought to occur through local hyperemia, massage analgesia, and reduction of adherent scar tissue [27]. Cryotherapy involves the application of cold (ice bags, ice massages, chemical cold packs, ice water immersion, ice circulating units, and vapocoolant sprays) to the injured area. This helps to reduce inflammation and swelling through vasoconstriction and decreased blood flow, as well as pain reduction through the gate control theory and by temporarily inhibiting effects to the neuromuscular system [28]. Although cryotherapy is beneficial in acute injuries, its efficacy in chronic injuries has not been as well studied [29]. Cryotherapy should be avoided in patients with cold hypersensitivity, cold intolerance, and Raynaud disease [30].
Low-level laser therapy (LLLT) uses light energy to induce ATP production, enhance cell function, increase protein synthesis, and to reduce inflammation, increase collagen synthesis, and angiogenesis. Laser sources are used at powers too low to cause measurable temperature increases, but should still not be used over cancerous areas, eyes, open wounds, pregnancy, or the epiphysis [31].
Therapeutic ultrasound is used for its nonthermal tissue healing effects and thermal effects. Low-frequency intensity ultrasound causes movement of fluids along cell membranes and formation of gas-filled bubbles, which is thought to promote tissue repair. At higher intensity, ultrasound also increases tissue temperature, reduces muscle spasm, and reduces pain. Contraindications include use over ischemic areas, deep vein thrombosis, anesthetic areas, actively infected areas, and over certain body parts such as the eyes, heart, skull, genitals, the trunk or abdomen in a pregnant woman, and over stress factors or osteoporotic areas [32].
Phonophoresis and iontophoresis use ultrasound energy and electrical pulse waves, respectively, to diffuse medication through the skin into affected areas. Commonly used medications are corticosteroids, lidocaine, salicylates, and acetic acid. Contraindications are similar to those of therapeutic ultrasound [33].
Extracorporeal shock-wave therapy (ESWT) delivers a single-impulse acoustic wave through an electromagnetic, electrohydraulic, or piezoelectric source [34]. The peak pressure of a shock wave is approximately 1000 times of an ultrasound wave. The mechanism of ESWT is not well understood. Some postulate that it stimulates production of angiogenic markers and neovascularization, while reducing calcitonin gene relayed peptide expression in dorsal root ganglions to induce tissue repair and regeneration [35].
Currently, the literature regarding the efficacy of the aforementioned physical modalities shows conflicting results and little evidence to support their use in treating tendinopathy, with the exception of ultrasound for calcific tendonitis and ESWT in calcific tendinopathy of the rotator cuff [21]. In addition, bracing/splinting is also a widely used treatment option [18].
Medication-based therapy usually includes NSAIDs, which work by inhibiting the cyclooxygenase (COX) pathway and by reducing the inflammatory response to injury [36]. Although few studies show that NSAIDS may be effective in relieving tendon pain in the short term (7–14 days), they may in fact be detrimental to the healing process by inhibiting the inflammatory response and thus normal tendon repair [21]. Pain control through NSAID use may also allow patients to ignore early symptoms, leading to further tendon damage and preventing definitive healing [37]. Furthermore, the side effects of NSAIDs are not insignificant in regard to the renal system, cardiovascular system, asthma exacerbation, and gastrointestinal bleeding, and should be used with caution in older patients with medical comorbidities. Thus, a short course of NSAIDs may be reasonable in acute tendon pain associated with inflammation (tendinitis/tenosynovitis) and perhaps early in a tendon overuse injury, but not in chronic treatment of tendinosis [7, 21, 35, 38].
Nitric oxide therapy may also be used in treating tendinopathy [39]. Nitric oxide (NO) is a soluble gas thought to be responsible for cell signaling and is synthesized by NO synthetase enzymes, which are up-regulated in tendon injury [40]. NO is postulated to enhance tendon collagen synthesis and tendon healing [41]. As such, research is ongoing regarding the efficacy of exogenous NO in the form of glyceryl trinitrate patches in treating tendinopathy, both for tendon healing, force, and pain. Three randomized, controlled, double-blind clinical studies by Paoloni and colleagues looked at whether transcutaneous administration of NO (glyceryl trinitrate patches) would enhance tendon healing in humans for treatment of lateral epicondylitis, Achilles tendinopathy, and rotator cuff tendinopathy. Treatment groups showed an improvement in pain, an increase in power, and an improvement function compared to controls [42–44]. The improvement persisted even at 3 years [45]. In 2010, Gambito et al. performed a meta-analysis on seven randomized clinical trials looking at the effects of topical nitroglycerin for tendinopathy treatment and found that it provides short-term pain relief and enhanced tendon forces in the chronic phase [46]. For now, topical glyceryl trinitrate for treatment of tendinopathy is still considered off-label by the Food and Drug Administration (FDA) and larger multicenter trials would be useful in validating this treatment modality.
Injection-based treatment includes injecting corticosteroid, platelet-rich plasma, whole autologous blood, prolotherapy, stem cells, and skin-derived tenocyte-like cells. Corticosteroid injections have remained the first-line approach to treating tendon pain through their anti-inflammatory effects [2, 47]. However, as tendinopathies frequently do not display an inflammatory state, it is not surprising that studies now show though corticosteroid injections help with pain initially [48]; they offer no intermediate or long-term benefit [3, 49–52].
A study by Newcomer et al. showed that there were no significant differences between corticosteroid injections and rehabilitation for lateral epicondylitis and that all patients had equal improvement in pain scores at 6 months [53]. A systematic review by Coombes et al. found that corticosteroids helped only with initial pain reduction in lateral epicondylitis and in rotator cuff pain [47]. Alvarez et al. found that a subacromial injection of betamethasone was no more effective than anesthetic alone in chronic rotator cuff tendinosis with regard to range of motion, quality of life, or impingement signs [48]. A systematic review by van Ark et al. found that corticosteroid injections had worse relapse pain rates when compared with physical therapy and other injection therapies at 6 months and beyond [54].
Although corticosteroids are still used as the first-line treatment of tendinopathy, they are not without risks or complications, and given the evidence in literature at this time, it seems that corticosteroid injections remain a good treatment for short-term symptoms, but may not be very helpful for long-term management.
Platelet-rich plasma (PRP) is a concentrate of platelets obtained from patient’s own blood that is centrifuged down to its various components. The PRP layer is then drawn off and re-injected into the site of injury to promote healing and regeneration by the action of growth factors and increased collagen expression, which leads to tendon cell proliferation and healing [55, 56].
So far, studies comparing the efficacy of PRP to various other treatments are still inconclusive. DeVos et al. showed that PRP injections did not improve pain or functional outcome in chronic Achilles tendinopathy compared to saline injection at 24 weeks or 1 year, nor did they change tendon structure or neovascularization based on ultrasound [57–59]. A systematic review by Paloloni et al. of human clinical trials did not find evidence that PRP injections were superior to other injections in treating tendon or ligament injuries [60]. However, a systematic review of in vivo studies by Taylor et al. showed some improvement, as well as studies by Peerbooms et al., which showed improvement in lateral epicondylitis pain compared to steroid. Gaweda et al. found improved pain and ultrasound parameters in Achilles tendinopathy [55, 61, 62]. However, Filardo et al. found no significant improvement in patients treated with PRP and physical therapy compared to physical therapy alone [63].
Similar to PRP, whole autologous blood injections are also thought to be rich in growth factors for cell proliferation and collagen regeneration [64, 65]. Although promising as a treatment option, more controlled research must first be done to determine efficacy and side effects [66–70]. Prolotherapy involves injecting proliferating agents (dextrose, phenol-glycerin-glucose, or sodium morrhuate) at painful tendon sites to induce an inflammatory response and lead to healing through tendon hypertrophy [71]. Again, given limited data, prolotherapy’s true efficacy is not yet known [72–76]. Skin-derived tenocyte-like cells is a novel approach that has only been explored in clinical pilot studies. Connell et al. injected autologous skin-derived tenocyte-like cells in patients with refractory lateral epicondylitis under ultrasound guidance and found that patients reported symptom improvement at 6 weeks, 3 months, and 6 months. Furthermore, ultrasound showed statistically significant changes in the number of tears, new vessels, and tendon thickness [77]. With the exception of corticosteroid injections, more studies are needed to determine the efficacy and side effects of the aforementioned injection therapies. Other procedures in the treatment of tendinopathy include injection of sclerosing medications, such as polidocanol injections, which destroy neovasculature to provide pain relief, and future therapies involving stem cell technology in tendon grafting and repair [7].