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Prolotherapy is very popular therapy in the field of sports medicine that involves the injection of a dextrose solution (sugar) into the body to help treat a variety of muscle, tendon, ligament and joint pains.  Although controversial with strong anecdotal evidence for its benefits and effectiveness to increase healing rates, reduce pain and the ability to reduce ligament laxity; to date there is still limited clinical evidence to support its use and particularly its long term effects. In this health news article we will briefly review; its


  1. History         

  2. How it Works         

  3. The Application of Prolotherapy

  4. Prolotherapy Solutions

  5. The Post Effects of Prolotherapy

  6. Adverse Effects of Prolotherapy

  7. Advantages and Disadvantages of Prolotherapy

  8. The Science of Prolotherapy

  9. The future role of Prolotherapy

1. Brief History

Research has shown that prolotherapy (originally called sclerotherapy) has been used for approximately over a century. However its modern use came to light in the 1950’s as it is considered to be a scar forming therapy. Since the 1950’s it has become popular in the field of professional sports for the treatment of acute ligament stretch injuries; - where the ligament has experienced a mechanical breakdown leading to laxity but not rupture.


Ankle and knee ligament injuries are often common in the field of sports such as those that participate in pivoting sports that involve running, cutting, hopping and landing such as football, alpine skiing or jumping on twin tip skies (1-6).


An injury of ligament laxity following a stretch injury can be present for a considerable long time or in certain cases may be everlasting leading to joint instability - causing long-term chronic pain and possibly joint degeneration. This may prevent the athlete to return to their chosen sport even after the original injury has healed affecting quality of life (7,8,9,10). Therefore the treatment of prolotherapy that is considered to increase the healing process and limit the ligament laxity can be very attractive both to the injured athlete and health professional to help return the athlete back to play.

2. How it works

Prolotherapy performs as a local irritant to generate an increase inflammatory response to help increase the protein synthesis and collagen formation thereby promoting an increase in cell proliferation. It is also considered to increase the infiltration of leukocytes (white blood cells) and macrophages (debris removers that ingest foreign particles) as well as to promote the platelet-derived growth factor (PGDF) and interleukin 1β IL-1β  (the chemical building blocks) to help advance and improve the ligaments mass, thickness and strength with a tendency toward an increase in cell number, glycosaminoglycan (protein) and water substance (11-15).  


The dosage and the number of Injections is often administered over a period of a few weeks or months depending on the severity of injury and health professional intuition.  The lack of consensus or standardisation and dosage protocols to administer the injections is a major deficiency in prolotherapy. 

3. The Application of Prolotherapy

The application of the irritant solution is administered by injections in and around the joint or muscle.

Syringe for Prolotherapy

4. Prolotherapy solutions

There are a number of solutions considered to stimulate the body’s ability to generate new tissue. However three solutions are often used In prolotherapy      

phenol-glucose-glycerin, D-glucose and sodium morrhuate.


D-glucose - It has been suggested that the safest solution is D-glucose despite conflicting evidence on it effects. Studies have shown an increase in proliferation (16) although other studies have shown cell death (cell apoptosis) (17).

Phenol-glucose-glycerin is considered to generate an increase in the inflammatory response. Although, phenol has also shown to be toxic to certain types of human cells (18) which may also block the peripheral nerves in humans (19).

Sodium Morrhuate - is an extract from cod liver oil and found to be toxic to erythrocytes (red blood cells) (20).


5. The post effects of Prolotherapy

The application of prolotherapy may often be painful depending where the injection is administered. The type of irritant solution and local inflammation may also cause discomfort and pain for up to 24 hours or even up to a week.  Post injection, patients are generally advised to rest and as required take analgesia but not anti-inflammatory medications. During the reactive inflammatory phase patients are also advised to avoid manual therapy. After the inflammation and pain has settled the injury site can be reassessed (e.g. the ligament can be reassessed for laxity and pain). The clinician will then use their intuition and professional judgment to decide whether or not further injections are required or whether the patient can begin rehabilitation.    


6. Adverse effects of Prolotherapy     

Despite the lack of clinical research, to date there has been no significant side effects apart from the post injection (i.e. flare of pain and tenderness of injection site).  However a study found that there may be some rare effects of prolotherapy such as nerve damage and allergic reactions although they were not classed as serious (21).   


Interestingly although only anecdotal, a renowned orthopaedic surgeon that often operates on elite professional athletes has observed athletes during surgery that had previously undergone prolotherapy injections around ligaments.  In some cases the surgeon witnessed that the ligament structure may generally change to a type III (soft fibrous) collagen structure opposed to the normal type 1 fibre (tough fibrous) collagen. Therefore it was hypothesised that prolotherapy may indeed help with the protein synthesis and the formation of collagen but at a type III (soft fibrous) collagen structure. Based on this observation this is not the ideal type of collagen (type III) for stabilising the ligament. Moreover it may well prevent the body’s natural ability to form and lay the type 1 collagen fibres via its own healing mechanisms (22-25).                      


7. Advantages and Disadvantages of Prolotherapy

Advantages - From reviewing the very limited anecdotal evidence available it does suggest it does have an advantage by helping to increase the healing process for acute ligament injuries where the ligament laxity improves quite rapidly. The athlete returns to their chosen sport sooner rather than a few weeks later due to the laxity being reduced or in certain cases completely.  This can be very attractive in elite professional sports but not so much in general sports. 


Disadvantages –  the disadvantages suggest from reviewing the anecdotal evidence that there may not be sufficient evidence or data to support prolotherapy in certain cases of chronic joint or muscle tendon pains.


8. The science of Prolotherapy

The lack of prolotherapy research is evident however much of the research has been performed on animal models. The research indicated signs of ligament thickening following medial collateral ligaments (MCL’s) prolotherapy treatments. However no significant difference was confirmed in strength or decrease in joint laxity (26). A further study showed that prolotherapy did create an increase in the inflammatory response that may potentially assist in cell proliferation. However this was not considerably different from injections of saline solution or general needle stick trauma (26).


A small randomised clinical trial compared intra-articular prolotherapy versus steroid injections to help reduce chronic sacroiliac joint pain.  The study outcome did show promising results that intra-articular prolotherapy helped to reduce chronic sacroiliac joint pain better than steroid injections, but unfortunately due to being a small study this cannot be generalised to the wider population (27).


A similar study also found positive results for the intervention of prolotherapy for treating sacroiliac joint pain but again this cannot be generalised to the wider population as the study was based on individual case studies with no control group (28). A systematic review study for chronic low back pain using prolotherapy as an intervention found contradictory results when used alone (29). However other studies found when prolotherapy was used in combination with other therapeutic interventions such as spinal mobilisations and exercise interventions, demonstrated a significant differences in the reduction of low back pain (30-31).  A systematic review of prolotherapy for musculoskeletal pain found that there was not sufficient data to support the use of prolotherapy for sport related soft tissue injuries and musculoskeletal conditions (32).


9. The future role of Prolotherapy

After briefly reviewing the limited literature available of prolotherapy, potentially it may have a future role in the clinical setting. However this would entirely depend on further research (i.e. high quality randomised controlled trials with non-injection arms) (33). The clinical studies should be specific to musculoskeletal and sport related conditions to help identify the future role and effectiveness of prolotherapy.  The aim of patient education is to confirm effective adherence to advised management and rehabilitation protocols for an effective, safe, accelerated recovery (34).  Therefore patients should be given a genuine account of rehabilitation protocols i.e. informed that the evidence of prolotherapy is still only anecdotal and be informed of any potential side effects (35-37).


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  11. Accessed Wikipedia - Platelet derived growth factors

  12. Accessed Wikipedia - The Interleukin 1 Family


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  16. Accessed Pub Med - An in situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength.


  18. Accessed Pub Med - Morphological and biochemical effects of sodium morrhuate on tendons.


  20. Access Pub Med - Vascular smooth muscle cells exhibit increased growth in response to elevated glucose

  21. Access Pub Med - High glucose and endothelial cell growth: novel effects independent of autocrine TGF-beta 1 and hyperosmolarity.

  22. Access to Pub Med - Phenol toxicity and conjugation in human colonic epithelial cells.

  23. Access to Pub Med - Peripheral nerve block with phenol to treat spasticity in spinal cord injured patients

  24. Access Pub Med - Sodium morrhuate stimulates granulocytes and damages erythrocytes and endothelial cells: probable mechanism of an adverse reaction during sclerotherapy.

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  27. Access HHS Public - Early Inflammatory Response of Knee Ligaments to Prolotherapy in a Rat Model

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  29. Access Pub Med - The use of prolotherapy in the sacroiliac joint.  

  30. Access Pub Med - Prolotherapy injections for chronic low-back pain.

  31. Ongley M, Klein R, Dorman T, et al. A new approach to the treatment of chronic low back pain. Lancet. 1987; 2: 143-146.

  32. Klein R, Eek B, DeLong W, et al. A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. J Spinal Disord. 1993; 6: 23-33.

  33. Access Pub Med - A systematic review of prolotherapy for chronic musculoskeletal pain.

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