Given the common nature of mid-portion Achilles tendinopathy, this author reviews the literature and shares insights on a variety of conservative modalities ranging from eccentric loading exercises and activity modification to prolotherapy injections and shockwave therapy.
Achilles tendinopathy is a common cause of pain and disability in people with an active lifestyle, particularly middle-aged men.1-5 The mid-portion of the Achilles (2 to 6 cm distal to the insertion) is the most commonly affected region.6 It is one of the most common sports overuse injuries, which repetitively load the Achilles tendon.1-3,7
Achilles tendinopathy has a 24 to 52 percent lifetime incidence in former runners and a current prevalence of 6.5 to 18 percent among runners.8,9 Mid-portion Achilles tendinopathy can also affect the sedentary population, suggesting that physical activity may exacerbate symptoms rather than cause them.10,11
This article will focus on Achilles tendinosis, the term employed when ultrasound reveals structural changes in the Achilles tendon, as this is by far the most common form of Achilles tendinopathy.12 Ruptures, peritendinopathy and insertional tendinopathy are outside the scope of this article.
Key Insights On Tendon Pathophysiology
An understanding of tendon pathophysiology is essential when you are considering treatment options. A number of studies in the last 10 years have shown that Achilles tendinopathy is largely a non-inflammatory process.13-19 In 2002, Khan and colleagues alerted all medical practitioners dealing with tendon injuries with the slogan “time to abandon the ‘tendinitis’ myth.”12 The four main events that occur in tendinopathy are cellular activation and increase in cell numbers; increase in ground substance; collagen disarray; and neovascularization.20
In situ intratendinous microdialysis studies have revealed no difference in concentrations of prostaglandin E2 (PGE2) between healthy tendons and tendons with tendinosis (i.e., there is no chemically mediated inflammatory process). Higher concentrations of glutamate (a powerful pain modulator) and lactate are also present in tendons with tendinosis in comparison to normal tendons.13,15,19
Researchers have conducted studies on tendons with tendinosis using gene technology (using complementary DNA (cDNA) arrays and real-time polymerase chain reaction (PCR)).16,21 These studies have found a down-regulation of matrix metalloproteinase-3 (MMP-3) and an up-regulation of type I and type III collagen, MMP-2 (the enzyme involved in degrading processes), the fibronectin receptor involved in healing processes (FNRB) and vascular endothelial growth factor (VEGF). There is also no regulation of genes for a variety of cytokines known to be involved in the inflammatory process.22
Following tendon injury, nitric oxide synthase (NOS) induces nitric oxide (NO) in rats. Research has shown NOS activity to be up-regulated in rat Achilles tendinopathy while tendon healing increases with the addition of more NO.23,24
While there is no chemically mediated inflammatory process, immunohistochemical analyses of tendon biopsies have revealed that there may be some neurogenic inflammation.13,25-27 Biopsies of areas of tendinosis with accompanying neovascularization have shown nerve structures in close proximity to vessels.26 Substance P (the pain neurotransmitter that also increases vascular permeability and vasodilatation) and neurokinin-1 receptor (the endogenous receptor for substance P) were also present in the vascular wall.27 This neural pathway associated with the neovascularization of tendinosis may explain the pain associated with this problem.20
What To Look For In The Examination
Typically, a patient will present with pain in the posterior ankle region. It generally is an insidious onset or it may be related to an increase in training. Classically, patients with Achilles tendinopathy present with post-static dyskinesia.28 Pain may also be present at the beginning of exercise. Pain will usually reduce with exercises although this ability to warm up will decrease with the increasing severity of tendinopathy. Pain will often return in the hours following exercise. There will usually be a visual thickening of the tendon.13
Mid-portion Achilles tendinopathy is usually a straightforward clinical diagnosis. A thorough history and observation of a thickened tendon should point to Achilles tendinopathy. Palpation of the tendon from proximal to distal with the patient lying prone and the ankle at approximately 70 to 90 degrees to the leg will reveal the area of tenderness. A double leg heel raise, single leg heel raise, hopping or running should also reproduce symptoms. One should also perform a thorough biomechanical evaluation including tests of calf flexibility, calf strength and gait analysis.
The VISA-A (Victorian Institute of Sports Assessment–Achilles) questionnaire may be a quantifiable measure of pain, stiffness and disability.29 It has good reliability, validity and stability.29 While it is mainly used for research purposes, the VISA-A is a questionnaire that one can use in the clinical setting to monitor patient progress.
The examiner should always be mindful of differential diagnoses. Significant swelling, crepitus and swelling that does not move with tendon movement are all classic signs of paratendinopathy.28 Other differential diagnoses include posterior ankle impingement, accessory soleus, deep flexor tendinopathy and referred pain.
How Diagnostic Imaging Can Be Beneficial In Ambiguous Cases Of Achilles Tendinopathy
As I mentioned earlier, mid-portion Achilles tendinopathy is usually a straightforward clinical diagnosis so diagnostic imaging is seldom required. However, imaging is useful in less clear-cut cases.
Ultrasound with color Doppler is my preferred imaging modality. Grayscale ultrasound will show fusiform thickening with or without focal hypoechoic areas.30 Color Doppler will often demonstrate neovascularization in the thickened part of the tendon. This usually occurs both inside and outside the ventral part of the tendon. However, in more severe cases, vessels can be visible through the entire thickness of the tendon.30
The disappearance of the neovessels may correlate to improvement in pain.31-33 Detection of neovessels, more so than detection of abnormalities in tendon structure with grayscale ultrasound, is operator dependent. Magnetic resonance imaging (MRI) will demonstrate tendon thickening and increased signal intensity.20,34 Signal intensity on MRI has been correlated with clinical outcome.34
Pertinent Treatment Considerations
Conservative treatment is recommended initially for all patients. Generally, this requires a multifactorial approach including activity modification (complete rest is not often required), strengthening and orthomechanical care (e.g., heel lifts, orthoses, footwear). In my experience, surgery for mid-portion tendinopathy is seldom required. It is now well established that anti-inflammatory agents will have no effect on tendinopathy other than short-term pain relief.
Activity modification and tendon loading are important concepts for both the patient and therapist to grasp. Some tendon loading activities are beneficial. Not enough or too much can be harmful. I will often tell my patients that 4 out of 10 is the “magic number” on a 0 to 10 visual analogue scale (VAS). Any pain below 4 is acceptable. If the pain goes above 4, the activity should stop.
Tendons also require a relatively constant load so look for a sudden change in tendon loading activities in the patient history. Be aware that athletes with a history of tendinopathy who undergo off-season surgery are prone to developing the problem again. A sudden decrease in tendon load associated with the recuperation from surgery in another area will put the tendon(s) at risk. For example, if the athlete is undergoing upper limb surgery, ensure that he or she continues with the Achilles tendinopathy treatment program.
How Patients Can Benefit From Eccentric Loading Exercises
While Curwin and Stanish first identified the importance of eccentric loading exercises in the treatment of tendinopathy, Alfredson and colleagues are credited with scientifically evaluating a 12-week program of eccentric loading exercises for mid-portion Achilles tendinopathy.3,35 //There are some significant aspects of the protocol of Alfredson and co-workers that one should stress to every patient.3
First, the protocol involves no concentric contraction of the affected side. The aim is to achieve a full eccentric range off the edge of a step with full body weight on the affected side. Ensure that patients start in a fully plantarflexed position (on tiptoes) on the affected side with no weight on the unaffected side. Patients should lower their feet down in a controlled manner until the ankle is in a fully dorsiflexed position. As soon as patients get into the fully dorsiflexed position, they return the unaffected foot to the step and remove the affected foot. Then they return to the starting position by concentrically contracting the unaffected side to return to the fully plantarflexed position.
Applying the “no concentric contraction on the affected side” rule can obviously be more difficult when the patient has bilateral pain. In these cases, I will ask patients to do the exercises on a staircase with handrails on both sides. In using this approach, when the ankle gets down into the fully dorsiflexed position, patients can push back up to the starting position using their arms, thus avoiding any concentric calf contraction. If they are unable to find the appropriate location or lack the upper body strength to do this, a compromise must occur. In these cases I will instruct patients to distribute their weight evenly across both feet to push back up concentrically to the starting position.
The second important factor with the eccentric loading exercise protocol is that pain is normal. As mentioned above, pain above 4 out of 10 on the VAS means the patient is loading the tendon too much. Pain below 4 out of 10 is normal and may even encourage tendon healing. The protocol that Alfredson and colleagues published was three sets of 15 repetitions of each exercise (straight and bent knee), twice daily for 12 weeks.3 One may need to adjust this for some patients in the early stages so their pain is below 4 on the visual analogue scale.
I also enforce the “no more pain than 4 out of 10” rule to other activities and exercise. I will usually allow patients to do some walking or running as long as they do not experience pain above 4 out of 10 on the VAS both during and after their exercise (particularly the morning after). One must explicitly state this to the patient: pain above 4 out of 10 will be detrimental while pain below 4 out of 10 will be beneficial. Also ensure the patient knows that the pain may get worse before it gets better. This phenomenon may be related to the damage to the neovessels in the early stages of treatment.
The “4 out of 10 pain rule” also comes into play in the latter part of treatment. When patients are able to complete the eccentric loading exercise program pain-free, encourage them to add weight in a backpack. As a guide, I would normally start with 10 pounds, which will often be enough to return to a level of painful training. Most athletic patients should be able to perform the exercises with 50 pounds in the backpack before they return to full sport. There is no set time to add weight. This is entirely dependent on the progress of the patient.
Here are some other points to advise patients on when giving them eccentric loading exercises.
Knee bent exercises. Ensure the knee is in a bent position (about 120 degrees) throughout the exercise. Patients who have poor thigh strength will tend to straighten the knee as they eccentrically lower the calf. They are also more likely to start with the foot closer to horizontal as opposed to being close to vertical.
Go barefoot where possible. As long as patients can tolerate it, I will encourage them to do the exercises barefoot. Sometimes the tongue of the shoe may compress the anterior ankle, which will stop the ankle from getting into a fully dorsiflexed position.
Speed of the eccentric drop. Ensure patients are lowering the foot with a controlled contraction. It should be smooth, not bouncy or jerky. One complete repetition should take about three seconds.
In a relatively low number of cases (I would estimate 10 to 20 percent) in which a combination of eccentric loading exercises, activity modification and orthomechanical care is unsuccessful, other treatment options are available. These include topical glyceryl trinitrate patches, sclerosing injections, prolotherapy injections, autologous blood or platelet rich plasma injections, and extracorporeal shockwave therapy. These therapies do not replace the aforementioned initial treatment protocol but are normally used as adjuncts.
Can Topical Glyceryl Trinitrate Have An Impact?
Researchers have shown the NOS activity to be upregulated in rat Achilles tendinopathy while tendon healing increases when additional NO is present.23,24 Patients have used glyceryl trinitrate patches in combination with eccentric loading exercises with success. Patients apply one-quarter of the patch (1.25 mg/day) to the affected area daily. Randomized controlled trials have shown improved outcomes over three months, six months and three years in comparison to placebo patches.36,37 At three years, the mean estimated effect size for all outcome measures was small at 0.21 (on a scale of 0 to 1).37
However, another randomized controlled trial showed no benefit of using topical glyceryl trinitrate patches in combination with eccentric loading exercises in comparison to eccentric loading exercises alone.38 Furthermore, histological samples taken during surgery in those who did not improve did not show any difference between the two groups. The main side effect with glyceryl trinitrate patches is headache. These patches are a relatively straightforward adjunct to eccentric loading exercises, which are easy for patients to manage.
What About Sclerosing Injections?
Polidocanol (Asclera™, Merz Aesthetics) is an aliphatic, non-ionized nitrogen-free substance with a sclerosing and anesthetic effect.4 Traditionally used to treat varicose veins, it causes vessel thrombosis by selectively affecting the vascular intima, even when injected outside the vessel.31 Polidocanol may also affect the nerves adjacent to the neovessels.
Both short-term and long-term studies show good results when an experienced radiologist performs the injection under ultrasound and color Doppler guidance.31,39,40 Lind and co-workers advocate a medial approach (to avoid the sural nerve), depositing small amounts of polidocanol (0.1 to 0.2 mL, 1 to 2 mL total) around the neovessels predominantly outside the ventral part of the tendon.31
Patients should rest for one to three days after the injection and only undertake light tendon-loading activities for two weeks.4
How Prolotherapy Injections Work
Prolotherapy is a simpler injection treatment and does not require ultrasound. With prolotherapy, one injects a solution of hypertonic glucose and local anesthetic alongside the painful areas of the tendon with the aim of stimulating inflammation followed by collagen deposition. Prolotherapy also aims to reverse the neovascularization accompanying tendinosis but this effect is still speculative.41
A recent three-arm randomized clinical trial compared prolotherapy injections used alone and in combination with eccentric loading to an eccentric loading only group.41//OK as is?// The combination treatment group had a more rapid response in comparison to the exercise group. While all three treatment groups improved over time, the combination group was statistically and clinically better than the exercise group at 12 months in almost every outcome measure. Patients received a maximum of 12 weekly injections around the tendon using a solution of 20% glucose/ 0.1% lidocaine/ 0.1% ropivacaine (Naropin®, APP Pharmaceuticals). Importantly, patients can maintain normal activities without any rest period post-injection throughout treatment. Prolotherapy, when combined with eccentric loading exercises, provided good value for money in the study.
Two studies also showed favorable outcomes for ultrasound-guided prolotherapy injection for mid-portion Achilles tendinopathy over the short and long-term.42,43 Patients received intratendinous injections of a 25% dextrose-lidocaine solution every six weeks with a median of five treatments needed.
What You Should Know About Autologous Blood Injections And PRP Injections
Autologous blood injections have recently gained popularity. A technician would draw a small amount of autologous blood from the antecubital fossa and inject the blood under ultrasound guidance into the area of maximum tendon pathology.44 This often occurs after dry needling of the tendon and under local anesthesia.45,46 The rationale is that introducing growth factor beta and basic fibroblast growth factors will act as humoral mediators to induce the healing cascade.44
Two cohort studies in patients with tennis elbow and one study on patellar tendinopathy demonstrate improvement in pain but no randomized control studies have been published.44-46 Researchers advised participants in these studies to stop sporting activities to reproduce symptoms for three months.
The recent introduction of platelet-rich plasma (PRP) injections raised hopes for tendinopathy treatment. The thinking was that the injection of higher concentrations of growth factors in comparison to autologous blood would provide increased benefits. A larger amount of blood (about 54 mL) is required and this mixes with citrate to prevent clotting, spins down in a centrifuge for 15 minutes and is buffered to match the pH of tendon tissue.47
However, a recent randomized controlled trial showed that PRP injections in combination with eccentric loading exercises were no better than saline injections and eccentric loading exercises for Achilles tendinopathy.47
What The Research Reveals About Shockwave Therapy
Extracorporeal shockwave therapy (ESWT) is usually categorized as either low-energy (2) or high-energy (> 0.2 mJ/mm2).46 Low energy ESWT such as the EMS Swiss DolorClast (EMS Electro Medical Systems) requires multiple treatments but is well tolerated and does not require anesthesia. High-energy ESWT devices such as the Dornier Epos lithotripter (Dornier MedTech) are more painful (often requiring anesthesia) although less treatments are required.48,49
Shockwave may work by inhibiting pain receptors and causing local cell death, stimulating new tissue formation.48-50 A randomized controlled trial comparing low energy ESWT to eccentric loading exercises and a control group showed that ESWT was comparable to eccentric loading exercises.49 No randomized controlled trials examining high-energy ESWT have been published although a case control study demonstrated that the treatment group had favorable results in comparison to the control group.48
Mid-portion Achilles tendinopathy is common in middle-aged athletes. Patients usually present with activity-related Achilles pain and post-static dyskinesia. A thorough patient history and clinical examination will often negate the need for diagnostic imaging. Achilles tendinopathy is a degenerative process. It is not an inflammatory process. Anti-inflammatory treatments may assist with pain but will not treat the underlying tendinopathy so one should avoid these treatments. Physical therapy including eccentric loading exercises and load modification will be a successful first-line treatment for most patients.
There are many adjunctive treatments that may assist those patients who fail to respond to physical therapy. More clinical trials are required to determine if some patients are better suited to one of these treatments over another. Surgery is seldom required and should be reserved for patients who fail to respond to conservative measures.
Dr. Sweeting is in private practice at Performance Podiatry and Physiotherapy in Queensland, Australia. He is a research fellow in the School of Medicine at the Logan and Gold Coast campuses of Griffith University in Australia and a lecturer the School of Podiatry at Queensland University of Technology.
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49. Rompe JD, Nafe B, Furia JP, et al. Eccentric loading, shock-wave treatment, or a wait-and-see policy for tendinopathy of the main body of tendo Achilles: A randomized controlled trial. Am J Sports Med 2007; 35(3):374-83.
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