Caring Medical - Where the world comes for ProlotherapyChronic ankle sprain and instability treatment

Ross Hauser, MD  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
David N. Woznica, MD | Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois
Katherine L. Worsnick, MPAS, PA-C  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
Danielle R. Steilen-Matias, MMS, PA-C | Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois

In this article we will discuss chronic ankle sprain treatment, the problems of diagnosing ankle sprains and long-term problems of ankle instability. We will discuss non-surgical options as well as surgical options for the treatment.

Highlights of this article:

  • Ankle instability caused by injured ligaments.
  • Ankle taping and bracing are not long-term options.
  • Surgical discussion.
  • Prolotherapy injection treatments, are they effective for non-surgical repair?

In our clinics we usually do not see patients who have just “twisted” an ankle. We usually see patients who have twisted their ankle many times and with each twist their ankle gets weaker and weaker and more unstable. When we see these patients, they usually walk in, sometimes barely, with chronic ankle pain, and a clear problem with maintaining a normal gait or walk. Many of these patients also have a great urgency to get back to a sport or job as quickly as possible, and they have an impatience with treatments they have tried and continually be recommended to that have not been effective.

Many times a patient will report that they had suffered numerous ankle sprains and did not seek medical attention because “the treatment is always the same and usually it is ineffective.”

Ankle Ligament InstabilityDiagnosis, treatment, and prevention of future ankle sprains can be tricky. Leading sports medicine researchers routinely write on the problem of helping patients with chronic ankle sprains. They have been writing about this problem with greater frequency for a long time.

In 2005, a study in the British journal of sports medicine (1) discussed the long term outcomes of inversion ankle injuries. (The most common type of ankle sprain is the “rolled” or “twisted” ankle, inversion injury, turning the ankle inward, injuring or tearing the ligaments on the lateral (outer) side of the ankle, usually the anterior talofibular and the tibiofibular ligaments.)

This 2005  study was cited by seven 2018 published studies to validate findings on the problems of identifying and treating ankle sprains and preventing these ankle sprains from becoming long-term problems.

Of those seven 2018 studies, one was a report on chronic ankle sprains prepared on elite college football players entering the National Football League.

That study from doctors at Tulane University School of Medicine,  Steadman Philippon Research Institute,  Drexel University College of Medicine, Harvard Medical School and the New England Patriots, found that prior ankle injuries were present in more than 50% of elite college football players attending the NFL Combine (pre-draft player workouts). The purpose of the study which was published in the Orthopaedic journal of sports medicine,(2) was to try to determine ways to prevent recurring ankle sprains.

Back to the 2005 study, the researchers addressed the same problem NFL teams were trying to avoid in 2018:

“Most patients who sustained an inversion ankle injury at sport and who were subsequently referred to a sports medicine clinic had persistent symptoms for at least two years after their injury.”

  • These two studies, separated by 13 years should give you an understanding as to why, your chronic ankle problem is just that, a chronic problem.

Fear and frustration in college age athletes going through rehabilitation

A study published in the Journal of sport rehabilitation (3) from American researchers at Still University and Old Dominion University wrote:

“Collegiate athletes with any history of ankle sprain exhibited elevated levels of fear compared to healthy controls. These findings suggest that ankle sprains in general may elevate injury-related fear but those with a history of recurrent sprains appear to be more vulnerable. Accordingly, fear should be addressed during rehabilitation.”

Rehabilitation focuses on balance and strength training. There is no question these exercises can help. Yet, chronic ankle instability remains a critical problem. For balance and strength training to be most effective the therapy must rely on resistance to build muscle. Muscle relies on strong tendons to hold itself to the bone. If the tendons are weak, the resistance is lower.  Muscles also rely on ligaments to hold the bones together so the tendons are in a maximum position to help the muscles get maximum resistance. If the ligaments and tendons, which are not addressed in physical therapy or any conservative treatments which we will discuss next, the physical therapy will not be a long lasting solution to chronic ankle sprain. In the section below on Prolotherapy we will address the problems of ligaments and tendons.

Is Fear and frustration cured with an ankle brace, an ankle sleeve, or a roll of tape?

A team of physical therapists in Spain have published a study (April 2018) in the journal Disability and rehabilitation. (4They wanted to report on their findings surrounding the immediate and prolonged (one week) effects of elastic bandage on balance control in subjects with chronic ankle instability.

  • Twenty-eight individuals: 14 were randomly assigned to the elastic bandage group (7 men, 7 women) and 14 were assigned to the non-standardized tape (typical white adhesive tape) group (9 men, 5 women).
  • This study did not observe differences between elastic bandage group and non-standardized tape group during the follow-up in the majority of measurements.
    • Elastic bandage of the ankle joint has no advantage as compared to the non-standardised tape.
    • The effects of the bandages could be due to a greater subjective sense of security. It is important to be prudent with the use of bandage, since a greater sense of safety could also bring with it a greater risk of injury.
    • The application of the bandage on subjects with chronic ankle instability should be prolonged and used alongside other physiotherapy treatments.

Caring Medical comment:

  • Short-term, ankle bandages and tape are to be used with caution.
  • A Long-term recommendation to keep the tape and bandage on because there is little else that can be offered is not a long-term solution.
  • In our opinion external structural support needs to be replaced by a rebuilding the internal structures of the ankle with simple Prolotherapy injections. We will cover this below.

“the treatment is always the same and usually it is ineffective.”

Sometimes when we ask a patient, how many times they have sprained their ankle, they will report that they really do not know. The patients will be able to review with us their medical history for ankle sprains as simply:

  • Scenario 1: Most times I did not go “get it checked out.” They (the ankle sprains) happen all the time. I know what to do for it.”
    • Usually the typical conservative care route is then followed:
      • Rest, get off the ankle as best you can
      • Immobilize, get the ankle taped up, braced up, put into a soft cast if necessary
      • Ice, lots of ice to get the swelling down
      • Anti-inflammatory medications

The patients will usually be able to describe  numerous occasions where they enacted their own self-care using any combination of these treatment protocols.

  • Scenario 2: I go to the doctor or emergency room or walk in immediate care center when the ankle sprain is really bad.
    • Here an examination of the ankle to rule out Grade three complete rupture of ankle ligament and possible ankle dislocation should be performed. In a severe ankle injury, peroneal tendon subluxation, the popping out of the two tendons on the outer side of the ankle should be discussed. Some of these patients were later recommended to surgery which we will discuss below.

Doctors are not sure if ankle sprains ever really heal – a “new sprain’ is probably just an old sprain that never healed

In the British Journal of Sports Medicine researchers say that a new ankle injury is not always a new or  acute one, but one that can be identified as an old, chronic injury with an increase in symptoms.(5)

Learning point:

  • A “new” ankle sprain may be an old ankle injury that went undetected and never healed.

The researchers of this study pointed out a scenario that we have seen frequently and many of the readers of this article can identify with:

  • An athlete/patient comes into a care center with an acute ankle injury.
    • In the medical history at the examination it comes out that the patient had a previous ankle injury but did not seek medical attention for it.
    • The patient reports that before this “acute” injury that caused them to seek medical help this time, they did have ankle pain.

The problem of treatment:

  • Since this is a “first time,” to the doctor injury, this is a “new injury,” despite the patient telling of a previous injury.
    • Doctors then would go to “first time,” treatment protocols that would not be as effective for a 2nd or 3rd or 4th ankle sprain event. The REST, ICE, anti-inflammatory treatments.
    • Further, if this was a 2nd or 3rd or 4th ankle sprain event, and the patient reported no pain between these injuries and his/her appearance in the doctors office that day, this would again be treated as a “new injury,” the REST, ICE, anti-inflammatory treatments would be first recommended.

The researchers suggested to doctors that these “new injuries,” should not be treated as new injuries but rather as gradual wear and tear overuse injuries. An old injury that never really healed and appropriate treatment should be explored for a chronic injury.

In our experience, this is a major reason why patients tell us “the treatment is always the same and usually ineffective.” Later in this article we will document our own research suggesting the treatment of patients with wear and tear and overuse ankle sprain injuries.

An ankle that never heals is forever unstable. This is where the surgical recommendation comes in

In the journal of Orthopaedics & traumatology, surgery & research, (6) Orthopedist researchers say not everyone with chronic ankle instability will need a surgery, however, in the course of providing conservative management of chronic ankle sprains, it is difficult to determine which of those patients will fail the treatment and will eventually need surgery.

  • “Most ankle sprains recover fully with non-operative treatment but 20-30% develop chronic ankle instability. Predicting which patients who sustain an ankle sprain will develop instability is difficult. “

If you are reading this article, it is very likely that you have, for the most part, failed conservative treatment and you are looking for answers.

Who will need the surgery and who will not? This may be determined by the level of the ankle instability.

Ankle instability may not show up after the first acute ankle sprain and there is no consensus on how to tell if a patient will have instability in the future, this much is the consensus in the medical community. But what is the progression from ankle sprain to ankle instability, can this be documented to offer some idea?

This was addressed by an Irish research team writing in the American Journal of Sports Medicine (7who among other findings found that patients who could not properly jump or land 2 weeks after their first lateral ankle sprain were high risk candidates for chronic ankle instability.

Unfortunately, literature examining chronic ankle instability is often conflicting and confusing to patients. The Irish researchers were able to identify jumping and landing ability and non-reported ankle pain up to 6 months as being high risk factors for ankle instability, but they were not the only factors.

University researchers in Australia also tackled this problem of identifying the risk factors for ankle instability. In June of 2016 the Australian team published their intent to examine the problems of ankle instability in the medical journal Systematic reviews (8) and correlate available research into a clearer understanding of key factors.. This was what they said:

  • “Ankle sprains are a significant clinical problem. Researchers have identified a multitude of factors contributing to the presence of recurrent ankle sprains including deficits in balance, postural control, kinematics, muscle activity, strength, range of motion, ligament laxity and bone/joint characteristics.

Unfortunately, the literature examining the presence of these factors in chronic ankle instability is conflicting.

  • As a result, researchers have attempted to integrate this evidence using systematic reviews to reach conclusions; however, readers are now faced with an increasing number of systematic review findings that are also conflicting. The overall aim of this review is to critically appraise the methodological quality of previous systematic reviews and pool this evidence to identify contributing factors to chronic ankle instability.”

In 2017, at the completion of their review, the researchers published their findings in the journal Sports medicine.(9)

  • Remarkably, only 17% of primary studies measured a clearly defined chronic ankle instability population.
    • COMMENT: In other words, research on chronic ankle instability in nearly 5 out of 6 studies, never clearly defined if the patients in the study actually had chronic ankle instability and to what levels.
  • “Evidence from previous systematic reviews does not accurately reflect the chronic ankle instability population. For treatment of non-specific ankle instability, clinicians should focus on dynamic balance, reaction time and strength deficits; however, these findings may not be translated to the chronic ankle instability population.”
    • COMMENT: In other words, you may not be getting the treatment you need for ligament deficiency. The ligaments are the stabilizer, the accelerators, and the strength of bone to bone interactions. Tendons are the stabilizer, the accelerators, and the strength of muscle to bone interactions.
    • In our opinion you need a treatment that strengthens and rebuilds your tendons and ligaments.

With focus on the ankle ligaments, here are the surgical recommendations and the challenges of surgery

In the patients we see, they have at some point considered surgical intervention for their chronic ankle instability because they are basically done with treatments that are not effective. The reason they have not jumped right to surgery is because of its risks and possibility that it will not help. But clearly, surgery does address ligament and tendon problems. These problems can also be addressed in a non-surgical manner as w will discuss below.

Whenever we discuss surgery, it is important to bring in a surgical opinion.

In the Journal of orthopaedic surgery and research, June 2018 (10) a team of Chinese medical university orthopedic surgeons presented their findings to the medical community:

  • “There is limited evidence to support any one surgical technique over another surgical technique for chronic lateral ankle instability, but based on the evidence, we could still get some conclusions:
    • (1) There are limitations to the use of dynamic tenodesis, which obtained poor clinical satisfaction and more subsequent sprains.
      • The goal of ankle tenodesis is to provide stability to the ankle my moving a weakened tendon to another place on the bone. The cost of this procedure is that you now have a much more limited range of motion in your ankle. This surgery fallen out of favor. s a side note, The American Orthopaedic Foot & Ankle Society website tells physicans “Tenodesis stabilization restricts laxity and pathologic motion but ignores the underlying ligamentous pathology causing the instability.” Simply you cannot treat the tendons without addressing the problem of the ankle ligaments.
    • (2) Non-anatomic reconstruction (the use of allograft (donated tendon) autograft (your tendon) or tenodesis to replicate the motion and stability abnormally increased inversion stiffness at the subtalar level as compare with anatomic repairment (Surgical repair of the ligaments)
    • (3) Multiple types of modified Brostrom procedures could acquire good clinical results.
      • modified Brostrom procedures are a group of surgical procedures that seeks to stabilize the ankle by repairing the anterior talofibular ligament. The main stabilizer ligament of the outer ankle. Brostrom procedure and its variants are the most popular surgery for ankle instability. But as stated above, there is limited evidence to support any one surgical technique over another surgical technique for chronic lateral ankle instability.

Surgery can work for some people. One of the appeals of the arthroscopic Brostrom procedure is that it is an “outpatient,” or same day surgery.  But as many have learned, same day surgery can mean months of rehabilitation. Typical rehabilitation of this procedure can include:

  • Immobilization for weeks or months
  • The problem of managing swelling with anti-inflammatory medications
  • Sleeping with a splint for weeks on end.
  • Months of therapy and treatment

Same day surgery simply means a smaller incision, the rehab remains the same.

Chronic ankle instability – is more than treating one ligament it is treating the whole ankle joint

In this section of our article we will present non-surgical options and the research behind them in repairing ligaments and tendon damage that may be occurring in the whole ankle. Surgery can be a successful remedy for some patients. However surgery can be limited in what it can fix at a single surgery and surgery, despite “claims of minimally invasive,” still requires a long rehabilitation afterwards. Ankle ligament reconstructive surgery is no different.

In the Journal of physical therapy science(11Doctors at South Korea’s Sport Science Institute, Incheon National University looked at male soccer players and found the complexity of the problem needed to be solved by addressing the entire ankle joint and not simply a ligament tear or chronic ligament weakness.

Here are their findings:

  • Over 70% of patients who experience ankle sprains report additional symptoms resembling chronic ankle instability, such as re-injury or ankle function abnormalities.
  • Chronic ankle instability has been connected to  reduced muscle strength and proprioception (ankle joint function as a whole) which interferes with postural control.
  • It is presumed that chronic ankle instability is caused by complex functional deterioration. It is not a simple solution.
  • Correcting ankle structure and muscle strengthening exercises are important for the rehabilitation of ankle instability. (In other words the ankle needs to be repaired and strengthened – the obvious goal of anyone suffering with chronic ankle instability).

A study from Dutch doctors publishing in the International journal of sports medicine (12looked at 98 patients with chronic, persistent ankle sprains. The problem of a single ligament causing ankle sprains and instability has now become a problem of total ankle joint destruction in these patients.

  • MRI revealed signs of developing ankle osteoarthritis (cartilage loss and osteophytes (bone spurs)),
  • Bone marrow edema is seen in the talocrural joint where the tibia, fibula and talus meet (TCJ) in 40% of the patients and in the talonavicular joint (TNJ) in 49% of the patients.

Chronic ankle sprains rapidly moves towards ankle instability and degenerative ankle disease. At this point the surgical options go from ligament reconstruction to the possibility of ankle fusion.

As a side note, one curious symptom and one that should clearly point to chronic ankle instability and should be explored in patients with chronic knee instability and hip instability is Dynamic balance problems related to the ankle.

In two studies from University College Dublin, patients who suffered from an acute ankle sprain were followed and tested for problems of balance. Not only were their injured ankles tested but also the same side knees and hips. At 6 months follow up (13) and one-year follow (14)  up after a single ankle sprain event, patients showed reduced balance that created stress on the entire limb side, hip, knee, and ankle included.

Ankle Instability and Prolotherapy

This section will deal with the question, How do WE treat chronic ankle sprains and instability?

Caring Medical’s first line of treatment for chronic ankle pain and ankle instability is Prolotherapy. In treating with Regenerative Injection Techniques (RIT), i.e., Prolotherapy, a comprehensive approach must be taken. This means treating the whole ankle, not just a single injection at a single site in the joint, as some physicians attempt to do. The comprehensive problem of ankle instability requires a comprehensive treatment. Here’s what current research reveals about ankle instability and injury and how a doctor should consider treatment:

Writing in the medical journal Practical Pain Management, we reported on 19 patients surveyed following Prolotherapy ankle treatments. These patients said they had less pain, stiffness, crepitating, depressed and anxious thoughts, medication usage, as well as improved range of motion, walking ability, sleep and exercise ability.

Of these 19 patients:

  • Patients reported an average of 3.3 years (40 months) of pain and on average saw more than three doctors before receiving Prolotherapy.
  • The average patient was taking at least one pain medication.
    • Sixty-three percent (12) stated that the consensus of their medical doctor(s) was that there were no other treatment options for their chronic pain.
  • Eleven percent (2) stated that the only other treatment option for their chronic ankle pain was surgery.

Prolotherapy effects

  • Patients received an average of 4.4 Prolotherapy treatments per ankle.
  • The average time of follow-up after their last Prolotherapy session was 21 months.
  • Patients were asked to rate their pain and stiffness levels on a scale of 1 to 10 on a visual analog scale (VAS) with 1 being no pain/stiffness and 10 being severe crippling pain/stiffness.
    • The 19 ankles had an average starting pain level of 7.9 and stiffness of 5.4.
    • Ending pain and stiffness levels were 1.6 and 1.5 respectively
    • Ninety-five percent reported a starting pain level of 6 or greater, while none had a starting pain level of four or less.
    • After Prolotherapy none had a pain level of 6 or greater, and 90% of patients reported at least a 50% reduction in pain.
    • One-hundred percent of patients stated their pain and stiffness was better after Prolotherapy.
    • Over 78% reported that pain and stiffness since their last session had not returned.

In regard to quality of life issues prior to receiving Prolotherapy:

  • 74% noted problems with walking, but only 37% experienced compromised walking after.
  • In regard to exercise ability before Prolotherapy, only 47% could exercise longer than 30 minutes, but after Prolotherapy this increased to 90%.
  • To a simple yes or no question, “Has Prolotherapy changed your life for the better,” all of the patients treated answered “yes.” This question was included in many of our studies, because when it comes down to the point of any medical treatment, we feel this is the point. It’s not “Is my x-ray better?” but rather, how has your life changed for the better.(15)

Good Ankle Prolotherapy Candidate

For significant deterioration, we may recommend to patients a more aggressive approach incorporating Platelet Rich Plasma and bone marrow aspirate stem cell treatments.

In the medical journal Clinical Medicine Insights Arthritis and Musculoskeletal Disorders, Caring Medical published our findings on seven patients receiving a combined bone marrow aspirate stem cell treatments. Patient case 1 represented an ankle case.

A 59-year-old female patient come into our office with right ankle pain following a lateral sprain. The patient reported she could barely walk without severe ankle pain.

The patient had unsuccessful treatment with cortisone injections and was being recommended to ankle fusion based on X-ray and MRI finding that suggested osteoarthritis, avascular necrosis of the talus, and synovitis. Please see our published research on bone marrow aspirate injections into the talus and case history of regenerative repair.

The patient received four bone marrow/dextrose treatments over a period of eight months.

  • At second treatment, the patient reported the ability to stand for long periods and walk for half a mile without pain.
  • At third treatment, she reported improved range of motion, less frequent pain, and ability to take two mile walks on hilly, uneven ground, although steep climbs still induced pain.

PRP Ankle Injection Research on high ankle sprain

A less common but well known ankle injury is the “high ankle sprain.” This is damage to the ligaments  that connect the shin bones tibia to the fibula. Because of the high impact stress at the tibia and fibula junction, the syndesmosis joint, the high ankle sprain is difficulty to heal. In recent research doctors examined the success of platelet-rich plasma (PRP) into the injured antero-inferior tibio-fibular ligaments (AITFL) in athletes on return to play (RTP). They further studied the issues of ankle instability and stability before and after the PRP ankle injections.

Sixteen elite athletes with AITFL tears were randomized to a treatment group receiving injections of PRP or to a control group. All patients followed an identical rehabilitation protocol and RTP criteria. Patients were prospectively evaluated for clinical ability to return to full activity and residual pain.

Here are the results:

  • Early diagnosis and treatment lead to shorter Return to Play
  • Significantly less residual pain upon return to activity was found in the PRP group;

CONCLUSIONS:
Athletes suffering from high ankle sprains benefit from ultrasound-guided PRP injections with a shorter RTP, re-stabilization of the syndesmosis joint and less long-term residual pain.(14)

Questions about chronic ankle sprain treatment options? Get help and inflammation from Caring Medical

Prolotherapy Specialists Chronic ankle sprain and instability treatment

References
1
Anandacoomarasamy A, Barnsley L. Long term outcomes of inversion ankle injuries. British journal of sports medicine. 2005 Mar 1;39(3):e14-. [Google Scholar]
2 Mulcahey MK, Bernhardson AS, Murphy CP, Chang A, Zajac T, Sanchez G, Sanchez A, Whalen JM, Price MD, Clanton TO, Provencher MT. The Epidemiology of Ankle Injuries Identified at the National Football League Combine, 2009-2015. Orthopaedic journal of sports medicine. 2018 Jul 17;6(7):2325967118786227. [Google Scholar]
3 Houston MN, Hoch JM, Hoch MC. 40 Collegiate athletes with ankle sprain history exhibit increased fear-avoidance beliefs. [Google Scholar]
4 Alguacil-Diego IM, de-la-Torre-Domingo C, López-Román A, Miangolarra-Page JC, Molina-Rueda F. Effect of elastic bandage on postural control in subjects with chronic ankle instability: a randomised clinical trial. Disability and rehabilitation. 2017 Jan 16:1-0. [Google Scholar]
Shrier I, Clarsen B, Verhagen E, Gordon K, Mellette J. Improving the accuracy of sports medicine surveillance: when is a subsequent event a new injury? Br J Sports Med. 2016 Jun 28. [Google Scholar]
Guillo S, Bauer T, Lee JW, Takao M, Kong SW, Stone JW, Mangone PG, Molloy A, Perera A, Pearce CJ, Michels F. Consensus in chronic ankle instability: aetiology, assessment, surgical indications and place for arthroscopy. Orthopaedics & traumatology: surgery & research. 2013 Dec 1;99(8):S411-9.  [Google Scholar]
7 Doherty C, Bleakley C, Hertel J, Caulfield B, Ryan J, Delahunt E. Recovery From a First-Time Lateral Ankle Sprain and the Predictors of Chronic Ankle Instability: A Prospective Cohort Analysis. Am J Sports Med. 2016 Feb 24. [Google Scholar]
8 Thompson C, Schabrun S, Romero R, Bialocerkowski A, Marshall P. Factors contributing to chronic ankle instability: a protocol for a systematic review of systematic reviews. Systematic reviews. 2016 Jun 7;5(1):94. [Google Scholar]
9 Thompson C, Schabrun S, Romero R, Bialocerkowski A, van Dieen J, Marshall P. Factors Contributing to Chronic Ankle Instability: A Systematic Review and Meta-Analysis of Systematic Reviews. Sports Medicine. 2017 Sep 8:1-7. [Google Scholar]
10 Cao Y, Hong Y, Xu Y, Zhu Y, Xu X. Surgical management of chronic lateral ankle instability: a meta-analysis. Journal of orthopaedic surgery and research. 2018 Dec;13(1):159. [Google Scholar]
11 Kim K, Jeon K. Development of an efficient rehabilitation exercise program for functional recovery in chronic ankle instability. Journal of Physical Therapy Science. 2016;28(5):1443-1447. [Google Scholar]
12 van Ochten JM, de Vries AD, van Putte N, Oei EH, Bindels PJ, Bierma-Zeinstra SM, van Middelkoop M. Association between Patient History and Physical Examination and Osteoarthritis after Ankle Sprain. International journal of sports medicine. 2017 Jul 24. [Google Scholar]
13 Doherty C, Bleakley C, Hertel J, Caulfield B, Ryan J, Delahunt E. Dynamic Balance Deficits 6 Months Following First-Time Acute Lateral Ankle Sprain: A Laboratory Analysis. J Orthop Sports Phys Ther. 2015 Aug;45(8):626-33. [Google Scholar]
14 Doherty C, Bleakley C, Hertel J, Caulfield B, Ryan J, Delahunt E. Dynamic balance deficits in individuals with chronic ankle instability compared to ankle sprain copers 1 year after a first-time lateral ankle sprain injury. Knee Surg Sports Traumatol Arthrosc. 2016 Apr;24(4):1086-95. [Google Scholar]
15 Hauser RA, Hauser, MA, Cukla J. Dextrose Prolotherapy Injections for Chronic Ankle Pain Practical PAIN MANAGEMENT, January/February 2010 p 70-76. [Google Scholar]
16 Laver L, Carmont MR, McConkey MO, Palmanovich E, Yaacobi E, Mann G, Nyska M, Kots E, Mei-Dan O. Plasma rich in growth factors (PRGF) as a treatment for high ankle sprain in elite athletes: a randomized control trial. Knee Surg Sports Traumatol Arthrosc. 2015 Nov;23(11):3383-92. [Google Scholar]

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