Non-operative method in the treatment of Achilles tendinosis and effect of NSAIDs in the healing of tendon:
Achilles tendon is the strongest tendon in the human body. Despite its strength, it is prone to injuries. Injury can happen to this tendon due to a sudden increase in the intensity of the activity, or due to overuse of the tendon. According to the Bone & Joint Journal, the terms tendinosis, tendonitis and tendinopathy have been used interchangeably for overlapping clinical and imaging abnormalities (Mitchell et al, 2009). In addition, the lesion should not be called tendonitis due to lack of histopathologically identifiable inflammatory, and the term tendinosis should be used to describe thickened tendon with abnormal signal when imaged by ultrasound or MRI. However, inflammation of tissue surrounding the tendon is observed in the case of paratenonitis. According to Li & Hua (2016), the disorders in the tendon are response to the failure of healing, which follows these three progressive stages: reactive tendinopathy, tendon disrepair, and degenerative tendinopathy. In addition, inflammatory response was also absent in these three stages. (Li & Hua, 2016, p. 1). In this paper, tendinopathy will be used to describe intratendinous disorders, which describes damaged or degenerating tendon. The current trend in the treatment of Achilles tendinopathy is to rest the injured tendon, stretch it, and use NSAID. NSAID is prescribed to reduce swelling, pain, and improve the healing process of the condition. Instead, NSAID can affect the repair process of the injured tendon and elongate the healing time. NSAIDs work by inhibiting the production of prostaglandins, and prostaglandins are involved in pain but also in the creation of collagen. So, the use of anti-inflammatory slows down the healing process (Tsai et. al, 2005). On the other hand, the use of eccentric exercise, to strengthen the tendon can induce the healing process of the tendon. Understanding that tendinopathy may not have inflammation of the tendon and the effect of NSAID can be crucial in managing the way a treatment is provided to the patient, and how we expect the condition to progress for Achilles tendinopathy.
Achilles tendon connects the plantaris, gastrocnemius, and soleus to the calcaneus bone. It connects the muscles of the calf to the heel. When we contract muscles, all the force goes through the tendon, at the point where it connects to the bone. So, the tendon must be strong, and it is elastic because it can store energy for running or jumping. It is made of different bundles and contains type-1 collagen fibers. Tendons can withstand a lot of repetitive loads, but if the tendon is strained for a long time or with load beyond its capacity, then it can get microtears. The degeneration of collagen fiber in response to chronic overuse is called tendinosis. The body can heal the microtears but if it is repeatedly strained, and the rate of degradation exceeds that of regeneration then, this could lead to the formation of scar tissue due to disrepair, and cause degradation of the tendon. The failure to heal tendon and formation of scar tissue which are not aligned like other collagen fiber results in weaker Achilles tendon. This can cause a tear or rupture in the tendon, which repeats the cycle of healing process, scar tissue, and further degradation of the tendon. There is also stiffness in Achilles tendon proximal to calcaneus bone, which is aggravated when walking after prolonged rest due to contraction and tightening of the tendon, and physical activity can strain the tendon and damage it. So, Achilles tendinosis can be characterized as a failure to heal the tendon, with formation of scar tissue, and continuous degradation of the tendon.
The structure and composition of tendons allow for their unique mechanical behavior. Just like concrete, the tendon can handle more stress than strain. Tendons also have viscoelastic properties, and their mechanical behavior is dependent on the rate of mechanical strain. So, the tendon is more deformable at low strain and allows it to absorb more mechanical energy. However, at high strain, it becomes stiff and less deformable, which helps in transmitting large muscular loads to the bone. But when the load exceeds its capacity, the tendon cannot transfer the energy by elongating furthermore, which leads to microtear and, has a chance to rupture the tendon. On the other hand, because of the viscoelastic nature of the tendon, the damage is further added when unloading, because the tendon tends to stay elongated more compared to the elongation it had from load of the same weight, which increases the time under strain of the tendon, resulting in additional injury, even when the load is removed (Thomas, 2018).
NSAIDs are prescribed to control the symptoms of Achilles tendinopathy, which can reduce the feeling of pain in patients. However, NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (Cox-1 and Cox-2), and these enzymes are involved in the synthesis of prostaglandins, which can promote inflammation (Ricciotti & FitzGerald, 2011). High levels of prostaglandins are produced at the site of injury. It also induces sensitivity to pain by lowering the pain threshold of nociceptors. Tendons are mostly made of strong type I collagen, which are aligned parallel to each other (Mostaco-Guidolin et al, 2017). When the tendon is damaged, type III collagen are formed at the site of injury. Unlike type I collagen, which are able to stretch considerably without breaking, type III collagen are very narrow and are more branching than parallel in orientation and, it forms the reticular fiber which supports the early synthesized extracellular matrix during wound healing and scar tissue. These scar tissues are formed as a part of the healing process, and as repair continues, the majority of type III collagen are replaced by the stronger type I collagen. Since NSAIDs inhibit the production of prostaglandin, it causes decreased pain sensitivity and increases the likelihood of damaging the newly formed immature scar tissues made of type III collagen, which are weak, by straining due to physical activity. During the maturation phase, the collagen shrinks and solidifies, and if the scar tissue does not heal properly then the collagen could be misaligned, which could cause the collagen fiber to not align in parallel orientation, making the tissue weaker and difficult to repair due to inactive status of the collagen (Cantu & Steffe, 2013).
In addition, NSAIDs are shown to be not effective in athletes with Achilles tendinopathy. They are only remedy for short term and treat the symptoms (pain) but it is not shown to help in the healing process of the injured tendon, and instead can further delay the process of healing due to repeated cycle of damaging the tendon. Astrom & Westin (2009) found no effect of piroxicam (NSAID) on Achilles tendinopathy. They conducted a double-blind randomized study, consisting of 70 adults with painful Achilles tendinopathy. The treatment group (35 people) were given piroxicam in the dosage of 40mg/day for 2 days, followed by 20mg/day for the following 2 days. They gave treatment in such order for 28 days with a period of increasing dosage followed by decreasing the dosage. The placebo group (35 people) were given placebo for 28 days. No other analgesics were used by the participants. Evaluation of muscle strength, swelling, pain, and residual symptoms were taken on 3, 7, 14, and 28 days of the experiment. They found that there were no differences seen between the two groups, and the overall results were similar. In the case of insertional Achilles tendinopathy there is also damage due to shearing forces. Shearing forces differ from high tensile loads mentioned above because there is not that large storage and release of energy but rather repetitive motion like kicking in swimming, where there is both dorsiflexion and plantarflexion of the foot. When there is continuous friction between the bone and tendon, it can cause inflammation of the bursa, which acts as a cushion between the tendon and the bone (Thomas, 2018). Patients with painful Achilles tendon are commonly diagnosed as retro-calcaneal bursitis, and paratenonitis. In both the placebo group, the swelling and pain went down to a lower level than the experimental group, even without the use of NSAID. This experiment shows that there may not be actual inflammation involved in Achilles tendon lesion, and NSAID may only provide temporary symptomatic relief, but it does not help in treating the condition in Achilles tendinopathy.
According to Marsola’s et. al (2003), use of NSAID does not prevent collagen degradation, nor does it help with the healing process of the tendon. They conducted an experiment on a rat. In their study, they assessed inflammation, mechanical property of Achilles tendon, and inflammatory cell accumulation. The tendon was surgically separated and allowed to heal with the use of NSAIDs. They observed that NSAID neither presented tissue damage nor help with the healing process. In this experiment, they believed that prostaglandin synthesis must have happened in paratenon, following tissue injury to explain the presence of leukocyte.
According to Su & Connor (2013), “In culture, NSAID treatment has repeatedly shown to inhibit proliferation and migration of tendon cells but increases collagen synthesis”. We know that after a tendon injury type III collagen are formed initially which are weaker that the type I collagen. In addition, when collagen type III, which are branched, mature, undergo normal healing process, they are replaced by type I collagen. Tsai et. al. (2005) showed that ibuprofen can inhibit the migration of tendon cells. They conducted an experiment with 20 Sprague Dawley rats. They obtained tendon cells from these rats; each tendon was cut into small pieces (1.5-2.0 mm3) and placed them in nutrient agar plate. Ibuprofen were added at the dosage of 0mg/ml, 0.1mg/ml, 0.2mg/ml, and 0.4mg/ml. The plate was stored at 37-degree Celsius in a humidified atmosphere. Initially tendon outgrowth was observed for control, 0.05mg/ml, and 0.1 mg/ml of ibuprofen. But the tendon outgrowth was not observed in 0.2mg/ml and 0.4mg/ml until the second and fourth day respectively. This demonstrates the effect of ibuprofen in delaying the outgrowth of tendon cells. Hence, the use of NSAID drugs inhibit the movement of tenocytes (tendon cells), and makes it difficult to repair the tendon, delays the healing, and reduces tendon strength, which results in progressive degeneration of Achilles tendon.
Therefore, early identification and treatment are necessary because there is a continuous degradation of the tendon in Achilles tendonitis, which can make the symptoms worse. Eccentric exercise has shown to improve the stiffness in Achilles tendon (Morrissey et. al, 2010). This study showed that eccentric training decreased tendon stiffness in individuals with Achilles Tendinopathy. Eccentric exercises help strengthen the tendon after the injury in a safe manner. Understanding that NSAID can treat the temporary symptom of this condition, but does not treat the condition itself, and knowing its impact on how it delays healing can help people make educated decisions themselves.
References:
Tendon Biomechanics. (2018, August 30). Physiopedia, . Retrieved from https://www.physio-pedia.com/index.php?title=Tendon_Biomechanics&oldid=197336.
Tendon Load and Capacity. (2019, September 20). Physiopedia, . Retrieved from https://www.physio-pedia.com/index.php?title=Tendon_Load_and_Capacity&oldid=223307.
Li, Hong-Yun., & Ying-Hui, Hua. (2016) Achilles Tendinopathy: Current Concepts about the Basic Science and Clinical Treatments. BioMed Research International, vol. 2016, 2016, p. 1. doi:10.1155/2016/6492597
Ricciotti, E., & FitzGerald, G. A. (2011). Prostaglandins and inflammation. Arteriosclerosis, thrombosis, and vascular biology, 31(5), 986–1000. doi:10.1161/ATVBAHA.110.207449
Mostaco-Guidolin, Leila., Rosin, Nicole L., & Hackett, Tillie-Louise. (2017) Imaging Collagen in Scar Tissue: Developments in Second Harmonic Generation Microscopy for Biomedical Applications. International Journal of Molecular Sciences, volume 18(8). 1772. https://doi.org/10.3390/ijms18081772
Cantu, Robert., Steffe, Jason A. (2013) Soft Tissue Healing Considerations After Surgery. Rehabilitation for the Postsurgical Orthopedic Patients, Third Edition, Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/scar-tissue
Mats, Åström., & Nils, Westlin. (2009) No effect of piroxicam on Achilles tendinopathy, Acta Orthopaedica Scandinavica, 63(6), 631-634, DOI: 10.1080/17453679209169724
Su, Bailey., & O’Connor, J. Patrick. (2013). NSAID therapy effects on healing of bone, tendon, and the enthesis. Journal of Applied Physiology, 115(6), 892-899. doi.org/10.1152/japplphysiol.00053.2013
Tsai, Wen-Chung, et al. (2005) “Ibuprofen Inhibition of Tendon Cell Migration and down-Regulation of Paxillin Expression.” Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, 24(3), 551–558. doi:10.1002/jor.20069
Marsolais, D., Côté, C., & Frenette, J. (2003). Nonsteroidal anti-inflammatory drug reduces neutrophil and macrophage accumulation but does not improve tendon regeneration. Laboratory Investigation; a Journal of Technical Methods and Pathology, 83(7), 991-999.
Kelly, M., Bucklin, M., Chimenti, R., Olson, R., Richards, M., Buckley, M., … Flemister, A. (2017). Novel Physical Therapy Protocol Results in Increased Compressive Strain and Improved Outcomes in Insertional Achilles Tendinopathy. Foot & Ankle Orthopaedics. https://doi.org/10.1177/2473011417S000238
Morrissey, D., Roskilly, A., Twycross-Lewis, R., Isinkaye, T., Screen, H., Woledge, R., & Bader, D. (2011). The effect of eccentric and concentric calf muscle training on Achilles tendon stiffness. Clinical Rehabilitation, Sage Journals 25(3), 238-247. doi-org.ccny-proxy1.libr.ccny.cuny.edu/10.1177/0269215510382600
Tenjing Sherpa 