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Prolotherapy (proliferative therapy), also know as sclerotherapy, ligament reconstruction therapy, and fibro-osseous injection therapy, is a recognized orthopedic procedure that stimulates the body’s nature healing processes to strengthen joints weakened by traumatic or over-use injury. Joints when ligaments or tendon attachments are stretched , torn, or fragmented, become hypermobile and painful. Traditional approaches with surgery and anti-inflammatory drugs often fail to stabilized the joint and relieve this pain permanently. Prolotherapy, with its unique ability to directly address the cause of the instability, can repair the weakened sites and produce new fibrous tissues, resulting in permanent stabilization of the joint. Prolotherapy can also be used to treat varicose veins, spider veins, hemorrhoids, other vascular abnormalities and other similar conditions.

Q: How does Prolotherapy work?
A: With a precise injection of a mild irritant solution directly on the site of the torn or stretched ligament or tendon, prolotherapy creates a mild, controlled injury that stimulates the body’s natural healing mechanisms to lay down new tissue on the weakened area. The mild inflammatory response that is created by the injection encourages growth of new ligament or tendon fibers, resulting in a tightening of the weakened structure. Additional treatments repeat this process, allowing a gradual buildup of tissue to restore the original strength to the area. Injection of varicose veins and other similar abnormalities creates a mild inflammatory response causing them to contract so that they become smaller or even vanish.

Q: What is in the solution that is injected?
A: The prolotherapy injections contain anesthetic agents and natural substances which stimulate the healing response. There are numerous substances, and each treating physician tailors the selection of substance according to the patient’s need.

Q: Is the Prolotherapy treatment painful?
A: Any pain involving an injection will vary according to the structure to be treated, the choice of solution, and the skill of the physician administering the injection. The treatment may result in mild swelling and stiffness. The mild discomfort passes fairly rapidly and can be reduced with pain relievers such as Tylenol. Anti-inflammatory drugs, such as aspirin and ibuprofen, should not be used for pain relief because their action suppresses the desired inflammatory process produced by the injection.

Q: Can Prolotherapy help everyone?
A: Each patient must be evaluated thoroughly with patient history, physical exam, X-ray exam, and full laboratory work up before treatment will be administered. With this information, your physician can evaluate your potential success with this therapy. Success depends on factors which include the history of damage to the patient, the patient’s overall health and ability to heal, and any underlying nutritional deficiencies that would impede the healing process.

Q: Who administers Prolotherapy?
A: Physicians who administer this form of therapy are trained by The American Osteopathic Association of Prolotherapy Regenerative Medicine. Postgraduate training is a prerequisite before treating any patient with a medical orthopedic problem, vein problem, or other condition which might benefit from prolotherapy.

Q: What areas of the body can be treated?
A: This form of therapy can be used to treat dislocation of the joints, knee pain, shoulder pain, Temporal Mandibular Joint dysfunction, Carpal Tunnel Syndrome, and disc problems at any level of the spine. The therapy affects only the area treated and does not cause any problem in any other area. Spider veins, abnormal or bulging veins and other similar conditions can be treated on the legs, feet, hands, arms, breast, face, and most other areas.

Q: How often do I need these treatments?
A: The treatments should be administered every one, two, or three weeks, as determined by your treating physician. Vein treatments are usually scheduled four or more weeks apart.

Q: What’s the rate of success in treatment?
A: The anticipated rate of success depends on a number of variables, including the patient’s history and ability to heal, and the type of solution used. In patients with low back pain with hypermobility, 85% to 95% of patienst treated experience remission of pain with this form of therapy. In comparison, the Journal of Bone and Joint Therapy reports on a 52% improvement in patients treated surgically for disc involvement. Varicose veins can usually be 90% to 100% eliminated. Spider veins can usually be improved 70% to 90%.

Tendinosis and Tendinitis

Research: Ibuprofen does not help tendinosis it may make it worse


This research came from the University of Copenhagen and was published in the Journal of Applied Physiology in November 2017.

Highlights of research

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat tendinopathy, but evidence for this treatment is lacking, and little is known regarding the effects of NSAIDs on human tendinopathic tendon.
  • This study investigated the effects of NSAID treatment (ibuprofen) on human tendinopathic tendon, with changes in gene expression (generally: Gene expression is your cells talking to each other or signalling each other that they need to heal something) as the primary outcome, and tendon pain, function, and blood flow as secondary outcomes.
  • Noteworthy of this research: “Nonsteroidal anti-inflammatory drugs are widely used in the treatment of tendinopathy, but little is known of the effects of these drugs on tendon tissue. We find that one week of ibuprofen treatment has no effect on gene expression of collagen and related growth factors in adult human tendinopathic tendon in vivo  . . . suggesting that tendinopathic cells are not responsive to ibuprofen.”

Ibuprofen does not stimulate healing in tendinosis – Ibuprofen may make your tendinopathy worse

In a May 2018 study published in the Journal of musculoskeletal disorders and treatment,  researchers at Rush University Medical Center offered these observations on an achilles injury in laboratory rats:

  • Post-tendon injury analgesia (pain relief) is often achieved with NSAIDs such as Ibuprofen, however there is increasing evidence that NSAID usage may interfere with the healing process.
  • We have examined the effect of oral Ibuprofen, on Achilles tendon healing in rat tendinopathy.
    • The rats received Ibuprofen 3 days after initial injury (acute cellular response phase – this is during the time of inflammation in response to injury) and continued for 22 days
    • or started at 9 days after injury (transition to matrix regeneration phase – this is the time of repair after the initial inflammatory phase) and given for 16 days.
    • Ibuprofen prevented key processes of the inflammatory response to healing. Including the processes of removing dead injured tissue and the process of rebuilding the damaged tendon. The researchers concluded that the use of Ibuprofen for pain relief during inflammatory phases of tendinopathy, might interfere with the normal processes of healing.

A multi-national team of researchers including those from Rutgers University, Virginia College of Osteopathic Medicine, and the University Regensburg Medical Centre in Germany tested the effects of Prolotherapy on tenocytes repair (tendon cells). Published in the journal Clinical orthopaedics and related research, what the team was looking for was how did Prolotherapy injections change the immune system’s response to a difficult to teal tendon injury.

These are the highlights:

  • Prolotherapy injections changed the cellular metabolic activity to a healing, regenerative environment in the tendon cells.
  • Prolotherapy activated RNA expression. The healing phase of soft tissue injury starts spontaneously after the tendon injury. Healing occurs  in three phases: inflammation, proliferation and maturation. RNA expression is the communication changes in genes (remember the gene expression from above)  that coordinates the beginning and ending of these three cycles of healing and injury repair process.
  • Activated Protein secretion – the process of rebuilding.
  • Cell migration. The ability of healing cells to get to the site of an injury, and the denial of damaging inflammatory factors from reaching the same site.

What is Osteoarthritis?


Degenerative joint disease should be considered a “whole” joint disease and not simply the loss of cartilage

Twenty years ago, an article published in Gerontology disagreed with the notion that wear and tear is the origin of osteoarthritis and conducted a literary review to prove that osteoarthritis starts with ligament damage. Reviewing numerous research articles, the authors conclude that subchondral bone (the bone just beneath cartilage) changes precede any cartilage change associated with osteoarthritis.

These bone changes are due to a loss of tension on bone at the ligament/bone insertion. In other words, ligament laxity causes bone changes that in turn cause cartilage change and damage. This idea appears again and again in the literature and this article – ligament laxity causes joint instability and degenerative joint disease.

When discussing knee osteoarthritis, the authors point to the importance of joint stability in the development of osteoarthritis.

“It should be remembered that the knee joint functions as an organ with every tissue contributing to its mechanical stability.  Ligaments, subchondral bone, meniscus and joint capsule all subserve the need for stability. . . the earliest change appears to be at the ligament-bone insertions site.  However, we propose that it is a change in the ligament that leads to an alteration in the tension on the bone at the bone-insertion site which precipitates bone remodeling (injury to subchondral bone) [emphasis added].”

 Taking account of the progression of osteoarthritis, it becomes clear that the ligament integrity or lack of integrity is what needs to be treated to prevent further joint destruction and this applies to all joints:

“The health and integrity of the overlying articular cartilage depends on the mechanical properties of its bony bed.  Ligament injury precedes the subchondral bone changes and these changes occur before articular cartilage degeneration. ‘The proposed reversal of the current concepts of the aetiology of osteoarthritis from cartilage to bone and ligament suggests that research and therapeutic strategies could be effectively redirected.”

That was twenty years ago and still pain management medicine continues to search for drugs, devices and surgical procedures to eliminate the chronic pain associated with osteoarthritis and degenerative joint disease and then fesses up that this is still not a fully understood science.


Research on Prolotherapy


A May 2020 study in the Annals of Family Medicine  made this simple statement at the conclusion of the research findings:

“Intra-articular dextrose prolotherapy injections reduced pain, improved function and quality of life in patients with knee osteoarthritis compared with blinded saline injections. The procedure is straightforward and safe; the adherence and satisfaction were high.”

In this study, the research team assessed their findings in 76 patients with knee osteoarthritis:

  • Patients were tested for pain and function at baseline.
  • The patients were then treated with Prolotherapy or saline at 4, 8, and then 16 weeks.
  • All outcomes were evaluated at baseline and at 16, 26, and 52 weeks.

Three treatments in a 12 week period and positive outcomes at 1 year. Prolotherapy reduced pain and improved function and quality of life. Further, the researchers noted: “Our findings are also consistent with other studies that have tested an intra-articular dextrose Prolotherapy protocol for knee osteoarthritis.” Let’s look at these other studies.

Another study from May 2020 published in The Journal of Alternative and Complementary Medicine made these observations:

  • The study included 66 patients aged 40-70 years with chronic knee pain that was not responding to conservative therapy and diagnosed as grade II or III knee osteoarthritis.
  • The patients were assigned to the dextrose prolotherapy group (22 patients), saline group (22 patients), or control group (22 patients).
  • The intra- and extra-articular dextrose prolotherapy and saline injections were administered at 0, 3, and 6 weeks. The patients were blinded to their injection group status.
  • A home-based exercise program was prescribed for all patients in all three groups.
  • Following pain and functional scoring outcomes, the researchers put their findings together and concluded: “These findings suggest that dextrose prolotherapy is effective at reducing pain and improving the functional status and quality of life in patients with knee osteoarthritis.

In January 2019, David Rabago, MD, of the University of Wisconsin School of Medicine and Public Health, published research on Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis in the Journal of Alternative and Complementary Medicine.

Here are the learning points of that research:

  • Patients received up to six prolotherapy sessions.
  • The primary data desired for analysis: Patient satisfaction with three or more prolotherapy sessions.
  • Secondary: Scoring assessment for improvement in function ability to get out of a chair, increase in walking ability, increase in the ability to climb stairs.
  • Of the patients who participated in the study: “Satisfaction was high.

The study concluded “(suggested) that Prolotherapy in this primary care clinic is feasible and acceptable.” In other words, it is beneficial to patients.

More of Dr. Rabago’s research is cited in this article as well as our own Caring Medical published findings.

Research: significant pain relief after Prolotherapy injections in patients suffering from knee osteoarthritis

In October 2017, a team of researchers from Shahid Beheshti University of Medical Sciences, Tehran, Iran published their findings in the Middle East Journal of Family Medicine  in which they found significant pain relief after Prolotherapy injections in patients suffering from knee osteoarthritis.

Here are the bullet points of the research:

Prolotherapy had a significant effect

  • The purpose of this study was to investigate the effect of dextrose injection on pain control associated with knee osteoarthritis.
  • The findings showed that injection of 15% and 25% of dextrose Prolotherapy had a significant effect on the visual (scoring scales) of pain and function of patients so that during treatment, (scoring scales) scales showed improvement in treatment in these patients.
  • Also, other findings showed that injection of 25% dextrose Prolotherapy compared to 15% had a significant effect on the visual analog scale of pain and function of patients.

The study was a single-blind clinical trial. (The patients did not know they were getting Prolotherapy).

  • 80 knee osteoarthritis patients referred to Taleghani Hospital in Iran.
  • Randomly divided into two groups: 15% dextrose injection and injection of hypertonic dextrose 25%.
  • the group of 25% Dextrose injection experienced more pain relief than the 15% group.
  • However, even a 10% solution, significant results could be achieved.

According to the results, it can be concluded that the mechanism of the effect of Dextrose Prolotherapy is direct effects, osmotic (growth in the number of cells), and inflammatory growth. Dextrose injection with a concentration of less than 10% still directly promotes cell and tissue proliferation without inflammatory reaction and a high concentration of 10% results in an extracellular osmotic gradient at the injection site resulting in loss of intracellular and lyse cellular cells (a breakdown of damaged cells) and the beneficial invasion of growth factors and inflammatory cells that start the wound healing cascade in that particular area.

Research: Prolotherapy treatments for patients with knee osteoarthritis showed significant improvement in scores for pain, function, and range of motion

  • In research from June 2017, doctors publishing in the British Medical Bulletin (7reviewed and evaluated Prolotherapy findings and determined Prolotherapy treatments for patients with knee osteoarthritis showed significant improvement in scores for pain, function, and range of motion, both in the short term and long term. Patient satisfaction was also high in these patients (82%).
  • Citing the previous research from Dr. Fariba Eslamian and Dr. Bahman Amouzandeh, they found that  Prolotherapy treatments in female patients with knee osteoarthritis resulted in significant improvement in pain, function, and range-of-motion scores.
    • In this study, they took 24 female patients with an average age of 58 (the youngest being 46 the oldest 70) and gave them three monthly Prolotherapy injections.
    • At the end of week 24 of the study, the knee range of motion increased, pain severity in rest and activity decreased. Improvements of all parameters were considerable until week 8 and were maintained throughout the study period.
  • In June 2017 research, doctors from the University of Wisconsin School of Medicine and Public Health write: Systematic review, including meta-analysis, and randomized controlled trials suggest that Prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and Prolotherapy was effective in overuse tendinopathy.
  • Doctors from the University of Wisconsin continued on their research into Prolotherapy. They found Prolotherapy resulted in the safe, significant, progressive improvement of knee pain, function and stiffness scores among most participants and continued as such at follow up an average of 2.5 years after initial treatment, this study from 2015.
    • This followed up on a 2013 study that appeared in the Archives of Physical Medicine and Rehabilitation  and suggested “Prolotherapy resulted in safe, substantial improvement in knee osteoarthritis-specific Quality of Life compared with control over 52 weeks. Among prolotherapy participants, but not controls, magnetic resonance imaging-assessed intra-articular cartilage volume change (intra-articular cartilage volume stability) predicted pain severity score change, suggesting that prolotherapy may have a pain-specific disease-modifying effect.”


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