Prolotherapy and Treatment Guidelines and Comprehensive review of Prolotherapy research.

Ross Hauser, MD. A comprehensive review of Prolotherapy research.

This article will cover information on Prolotherapy including general questions on Prolotherapy treatments, side effects, research, reviews, and medical studies.

Prolotherapy has been utilized in clinical practices for over 80 years. Standardized and reviewed in clinical application by Dr. George Hackett in the 1950s, prolotherapy has been shown to be an effective treatment in patients who suffer from joint instability due to ligament damage and overuse and related musculoskeletal and osteoarthritis.

Prolotherapy’s popularity as a treatment for chronic pain has intensified over the past two decades among both physicians and patients as clinical and anecdotal observations has proved in many cases its reliance as a non-surgical option for joint and back pain.

The discussion subjects of this article on Prolotherapy reviews and research examinations:

What is Prolotherapy?

Prolotherapy is a nonsurgical regenerative injection technique that introduces small amounts of an irritant solution to the site of painful and degenerated tendon insertions (entheses), joints, ligaments, and in adjacent joint spaces during several treatment sessions to promote growth of normal cells and tissues.

Irritant solutions most often contain dextrose (d-glucose), a natural form of glucose normally found in the body, but may also contain combinations of polidocanol, manganese, zinc, pumice, ozone, glycerin, or phenol.

In severe cases, autologous cellular solutions may also be needed, such as platelet-rich plasma (PRP), bone marrow, or adipose tissue.

For the patient, the goal of Prolotherapy in chronic musculoskeletal pain and instability is the stimulation of body’s natural healing and regenerative processes in the joint that will facilitate the repair and regrowth of connective tissue, ligaments, tendons for tensile strength, and cartilage and other joint stabilizing structures such as labral tissue.

Prolotherapy works by the same process that the human body naturally uses to stimulate the body’s healing system, a process called inflammation. The technique involves the injection of a proliferant (a mild irritant solution) that causes an inflammatory response which “turns on” the healing process. The growth of new ligament and tendon tissue is then stimulated. The ligaments and tendons produced after Prolotherapy appear much the same as normal tissues, except that they are thicker, stronger, and contain fibers of varying thickness, testifying to the new and ongoing creation of tissue. This is documented in the research below.

Learning points

While we treat with H3 Prolotherapy methods we will refer to these treatments simply as Prolotherapy for the remainder of this article.

Is Prolotherapy like cortisone? 

Prolotherapy is a regenerative injection treatment used to treat joint and spine pain by repairing damaged and weakened ligaments and tendons.

Principle findings reveal that dextrose prolotherapy has a clear and positive effect on chronic musculoskeletal pain ranging from 6 months to 1 year.

A December 2020 study in the journal Anesthesia and Pain Medicine (1) made these observations on prolotherapy treatment:

Prolotherapy Treatment Goals

What are the goals of Prolotherapy treatments?

What are in Prolotherapy injections?

The Prolotherapy technique we use at Caring Medical is called Comprehensive Prolotherapy or Hackett-Hemwall-Hauser (H3) Prolotherapy. This type of Prolotherapy incorporates the teaching and techniques of doctors George S. Hackett, MD, and Gustav A. Hemwall, MD, two of the pioneers in the field, as well as developments made in our 3 decades of clinical experience and analysis of results.

The primary ingredient in Prolotherapy injections used at Caring Medical is dextrose. How does dextrose accelerate healing?

This technique involves using the simple and safe base solution dextrose as the primary proliferant, along with an anesthetic (such as procaine or lidocaine), that is given into and around the entire painful/injured area(s). Many injections are given during each treatment, versus just a few injections. Most treatments are provided every 4 to 6 weeks to allow time for the growth of new connective tissues.

In these basic Prolotherapy injection solutions, we also use an alkaline extract of the pitcher plant called Sarapin. Almost all pain issues have some kind of nerve component, which Sarapin helps to relieve. In our experience, Sarapin enhances the healing effects of injection treatments and has an excellent safety profile. It is one of the few materials found in the Physicians’ Desk Reference that has no known side effect. Also in the basic solution, to help ease the pain of the injection procedure, as well as provide pain relief to the area, procaine or lidocaine is added in very small quantities. Often, this helps to ease the pain right away after the procedure, but is used in such a small amount to not cause any adverse effect to the joint repair/wound healing cascade.

With a comprehensive approach, we utilize many different types of Prolotherapy solutions, individualizing each treatment according to the patients’ unique needs. The solutions are changed depending on the individual patient and the amount of inflammatory reaction required to produce sufficient healing and new collagen growth. We also use cellular proliferants such as blood, PRP (platelet rich plasma), bone marrow, and stem cells.

As with other medical procedures, Prolotherapy is a specialty. If you are looking into Prolotherapy, you first want to make sure that the Prolotherapy doctor or Prolotherapist experienced in the Comprehensive Prolotherapy procedure and has successfully treated cases like yours.

PRP and PRP Prolotherapy

A January 2021 study in the journal Anesthesia and pain medicine (2) “found that PRP and dextrose prolotherapy were shown to be effective for treating degenerative conditions and injuries. Both PRP therapy and prolotherapy commonly have regenerative therapeutic properties, but the central mechanisms of prolotherapy and PRP are different.

In prolotherapy, hyperosmolar dextrose triggers an inflammatory response, increases platelet-derived growth factor expression, and upregulates several mitogenic factors that may act as signaling mechanisms in tendon repair. In PRP therapy, it aims to augment the natural healing process of tendon repair and regeneration by delivering high concentrations of growth factors directly to a lesion.”

In other words, Prolotherapy does not act directly as a patch on a tear but rather is initiates a new and natural healing response to injury. PRP does act in a “patch-like” method to repair a tear. It is this understanding of these two treatments which leads us to use both treatments to help the patients.

For more information on these treatments please see our articles:

Video: What type of treatment do I need?

In this video, Danielle R. Steilen-Matias, MMS, PA-C, offers a brief introduction to treatments. Explanatory and summary notes are below:

A major factor in determining which treatment to get is the extent of your injury and whether this is a recent injury or a problem with degenerative joint disease or degenerative arthritis.

What is the evidence for Prolotherapy?

For patients who are looking into Prolotherapy, please understand that this is a specialty procedure with technique and experience being a key component. What we present on our website is based on our experience and research and does not apply to all practitioners or injection therapies.

In July 2016, our doctors at Caring Medical published findings on the effectiveness of Prolotherapy treatments in the medical journal: Clinical Insights: Arthritis and Musculoskeletal Disorders, (3) here are the summary highlights:

Our doctors reviewed 32 studies on dextrose prolotherapy for chronic musculoskeletal pain. The following conclusions are made:

Overall, Prolotherapy has been demonstrated to be efficacious and should be considered as a treatment for pain and dysfunction associated with chronic musculoskeletal conditions, particularly tendinopathies and osteoarthritis.


Prolotherapy for Knee Pain

In this image of a patient being prepped for an receiving Prolotherapy injections into their knee, the dots on the skin represent those areas of the knee that should receive an injection. In this particular patient, there are 50 dots on their knee. Each dot would represent where each injection would be given. This is one comprehensive Prolotherapy treatment to the knee. 

In this image of a patient being prepped for receiving Prolotherapy injections into their knee, the dots on the skin represent those areas of the knee that should receive an injection. In this particular patient, there are 50 dots on their knee. Each dot would represent where each injection would be given. This is one comprehensive Prolotherapy treatment to the knee. 

Published research papers from our doctors at Caring Medical on Knee Disorders

Recent Prolotherapy knee research

Prolotherapy for Knee Osteoarthritis

A June 2022 study in the journal Clinical rehabilitation (70) “assessed the effectiveness, compliance, and safety of dextrose prolotherapy for patients with knee osteoarthritis.” Researchers gathered data from 14 previously published studies with a combined 978 patients. The researchers found: “Compared with placebo injection and noninvasive control therapy, dextrose prolotherapy had favorable effects on pain, global function, and quality of life during the overall follow-up. Dextrose prolotherapy yielded greater reductions in pain score over each follow-up duration than did the placebo. Compared with other invasive therapies, dextrose prolotherapy generally achieved comparable effects on pain and functional outcomes for each follow-up duration.”

Led by researchers at the University of California at Los Angeles (UCLA) and the Department of Biological Sciences, at the University of Southern California (USC) a June 2021 paper in the medical journal Cartilage (4) offered these observations:

“Hypertonic dextrose injections (prolotherapy) for osteoarthritis are reported to (be able to) reduce pain. Cartilage regeneration is hypothesized as a mechanism. This in vitro study identifies a Prolotherapy concentration that stimulates chondrogenic cells to increase metabolic activity and assesses whether this concentration affects collagen deposition and proliferation.”

What the researchers are doing is taking hypertonic dextrose (a concentrate simple sugar, the main ingredient in the Prolotherapy solution) to see if, in a lab setting, they can grow cartilage cells with it. This was their observation.

(Prolotherapy)  “solution appears to be associated with the increased metabolic activity of chondrocytes (reproduction of the cells that make cartilage), increased collagen deposition, and increased chondrocyte proliferation. These results support clinical prolotherapy research suggesting that intra-articular Hypertonic dextrose joint injections reduce knee pain. Further study of Hypertonic dextrose injections and cellular processes is warranted.”

A May 2020 study in the Annals of Family Medicine (5) made this simple statement at the conclusion of the research findings:

Another study from May 2020 published in The Journal of Alternative and Complementary Medicine (6) made these observations:

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. (7) The study concluded:

May increase joint space

A January 2022 study (17) found that knee osteoarthritis patients receiving hypertonic dextrose prolotherapy had improvement of knee pain, stiffness, and function and increasing tendency in the medial minimum joint space width.

Compared to hyaluronic acid

A November 2021 study (18) found: “(Prolotherapy) appears to be an effective intervention to decrease pain and improve function in knee osteoarthritis, with efficacy similar to intra-articular injections with hyaluronic acid in the short-term follow-up.”

Prolotherapy treatment significantly improved total pain and knee function compared with control groups.

An August 2021 study in the journal Aging Clinical and Experimental Research (20) reviewed and analyzed Prolotherapy injections for the treatment of knee osteoarthritis. Their findings were that at an average 23 weeks follow-up, Prolotherapy treatment significantly improved total pain and knee function compared with control groups. There were no severe adverse events related to dextrose injection reported in all the included studies. Prolotherapy is a promising treatment for knee osteoarthritis with a reasonable safety profile.

Dextrose prolotherapy may be considered in knee osteoarthritis

A May 2021 study in the Journal of Clinical Orthopaedics and Trauma (8) wrote: “Prolotherapy in knee osteoarthritis confers potential benefits for pain but the studies are at high risk of bias. Based on two well-designed studies, dextrose Prolotherapy may be considered in knee osteoarthritis (strength of recommendation B). This treatment is safe and may be considered in patients with limited alternative options (strength of recommendation C).”

Basically, Prolotherapy appears to be helpful, it would be better if these researchers had more research to review.

Prolotherapy for knee pain patients not responding to conventional care

A May 2020 study in The Journal of Alternative and Complementary Medicine (27) of 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 were divided into three different groups, 22 patients received dextrose Prolotherapy, 22 patients received saline injections, and 22 patients received were used as a control group.

Prolotherapy injections in and around the knee

Doctors writing in the Journal of Pain Research (54) found that patients who received Prolotherapy with dextrose periarticular injections around the knee joint with patients who received Prolotherapy intra-articular injections. In other words, one group received injections around the knee joint, another group received injections directly into the knee joint.

Prolotherapy rebuilds and protects cartilage in the knees

A December 2021 paper in the journal Cartilage (23) tested the idea that Prolotherapy can reduce knee pain by growing cartilage. This was a laboratory experience to see if a dextrose solution similar to that used in Prolotherapy, could grow cartilage in a laboratory setting. The researchers found: “(Dextrose) appears to be associated with the increased metabolic activity of chondrocytes, increased collagen deposition, and increased chondrocyte proliferation. These results support clinical Prolotherapy research suggesting that intra-articular (dextrose) joint injections reduce knee pain.

A May 2021 paper in the Journal of Rehabilitation Medicine (25) found: “Dextrose Prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection.” Higher urinary C-terminal telopeptides of type II collagen are seen as markers of cartilage breakdown that occurs in early cartilage degradation.

A 2015 study published in the journal Therapeutic Advances in Musculoskeletal Disease (61) described Prolotherapy’s ability to rebuild soft tissue and cartilage. 

Ozone Prolotherapy for knee osteoarthritis 

An August 2021 study (21) in the journal Evidence-Based Complementary and Alternative Medicine compared the effect of hypertonic saline with ozone plus hypertonic saline in improving the symptoms of osteoarthritis in the patients. The results showed that intra-articular prolozone therapy and hypertonic saline injection can lead to improvement of pain and function in patients with knee osteoarthritis at the same status without any significant difference. Note that dextrose was replaced with saline.

A November 2020 study in the journal Anesthesiology and Pain Medicine (22) wrote that “for patients with knee osteoarthritis, Prolotherapy with ozone plus hypertonic dextrose and somatropin was more effective in sedating the pain and improving the stiffness and function of the knee than dextrose and somatropin alone.”

Prolotherapy compared to PRP in the treatment of knee osteoarthritis

Results of the present study suggested a significant decrease in the overall WOMAC score of patients who undergo either PRP therapy or PRL. This positive change in the overall WOMAC score led to an improvement in the quality of life of patients with knee OA shortly after the first injection. PRP injection is more effective than PRL in the treatment of knee OA.

A January 2018 study in the Clinical Interventions in Aging (26) when comparing Prolotherapy to PRP injections “suggested a significant decrease in the overall (pain and disability) score of patients who undergo either PRP therapy or Prolotherapy. This positive change in the overall (pain and disability) score led to an improvement in the quality of life of patients with knee osteoarthritis shortly after the first injection. PRP injection is more effective than Prolotherapy in the treatment of knee osteoarthritis.”

August 2019 in the journal Advances in Rheumatology (28) wrote: “In terms of pain reduction and function improvement, Prolotherapy with hypertonic dextrose was more effective than (injections of) local anesthetics, as effective as (injections of) hyaluronic acid, ozone or (treatment of) radiofrequency and less effective than PRP and erythropoietin (hormone protein that stimulates red blood production), with a beneficial effect in the short, medium and long term. In addition, no side effects or serious adverse reactions were reported in patients treated with hypertonic dextrose. Although hypertonic dextrose Prolotherapy seems to be a promising interventional treatment for knee osteoarthritis, more studies with better methodological quality and low risk of bias are needed to confirm the efficacy and safety of this intervention.”

Prolotherapy for sports-related knee ligament injuries

Prolotherapy for an ACL tear

In 2009, Prolotherapy doctors led by Walter Grote MD published a case history of an 18-year old female patient who returned to sports after a high-grade partial (possibly complete) ACL rupture.

This case report, published in the medical journal International Musculoskeletal Medicine, documented the successful non-surgical repair of an MRI-confirmed high grade or total ACL tear in an 18-year-old female with knee laxity and instability using Prolotherapy and at-home exercise. After treatment, the patient regained full knee function, resumed normal activity, and returned to recreational sport. Post-treatment MRI revealed a healing chronic ACL tear. These findings are notable given that surgical ACL reconstruction is the conventional treatment for ACL tears with such clinical presentation.

As exciting as this sounds, Dr. Grote and colleagues noted that there were too many factors in this ACL healing to confirm it was caused by Prolotherapy treatment alone. They questioned first of all was the MRI of a complete ACL rupture even accurate? (68)

24-year-old soccer player with knee instability

A case study was reported in the American Journal of Physical Medicine & Rehabilitation in April 2020. (67) A 24-yr-old male soccer player with a seven-year history of left posterior knee “looseness” came in for examination. At the time of initial injury, the patient suffered from atraumatic anterior and posterior cruciate ligament sprains. Seven years the patient now described knee pain as a constant, dull ache, a 3 out of ten pain. His biggest complaint however was this feeling of “instability” and looseness where his knee would “buckle” 3-4 times a week.

Physical examination was positive for grade 1 posterior drawer and grade 1 posterior sag signs (signs of a partial tear).  The sonographic evaluation confirmed magnetic resonance imaging findings of posterior cruciate ligament laxity and buckling and a small cystic lesion pressing against the posterior cruciate ligament.  After a trial of physical therapy, the patient received dextrose hyperosmolar (Prolotherapy) solution. This resulted in the resolution of the cyst and the patient’s subjective feeling of looseness and instability was resolved by seven weeks.

In 2003, K. Dean Reeves, MD published his findings of the effect of Prolotherapy on ACL tears in the Alternative Therapies in Health and Medicine (69)

Study Summary:

Prolotherapy for Osgood-Schlatter disease

An October 2021 study in the Archives of Orthopaedic and Trauma Surgery (19) compared Prolotherapy to saline placebo. “After three injections, at the 6-month and 12-month follow-up visits, the (pain and function) scores of the two groups were significantly improved; the dextrose group score was better than the saline group score, and there were significant differences between the two groups.”

Prolotherapy for Chronic Patellar tendinopathy

A November 2020 study in the Journal of Experimental Orthopaedics (49) examined the use of Prolotherapy and Sclerotherapy injections. A note of understanding. At one time Prolotherapy and Sclerotherapy were used as somewhat synonymous terms. They are however not the same treatment. Prolotherapy injections center on the joints with the repair of the tendon, ligaments, and cartilage. Sclerotherapy focuses on the blood vessels and is considered a treatment for varicose veins. The findings: The researchers examined ten previously published papers and found positive results with an increase in functional ability scores and decreases in pain scores in the patients examined. “Among all ten studies, no serious adverse events were reported. Based on this limited set of studies, there seems to be some evidence that Sclerotherapy and Prolotherapy may be effective treatment options to treat pain and to improve function in patients with Chronic Patellar tendinopathy.”

Prolotherapy for Back Pain

Published research papers from our doctors at Caring Medical on low back pain

Lumbar instability as an etiology of low back pain and its treatment by prolotherapy

In December 2021, our peer review paper Lumbar instability as an etiology of low back pain and its treatment by Prolotherapy: A review was published in the Journal of Back and Musculoskeletal Rehabilitation (29) was published. For the full version or abbreviated lay version please see our article Prolotherapy treatments for lumbar instability and low back pain.

The main theme of this article is treating low back pain with Prolotherapy. These are some of the previously published papers we used as source information.

Research:

Research:

Sustained pain reduction has been demonstrated in a prospective consecutive patient series in which the effects of disc space injections of hypertonic dextrose were assessed in patients with chronic advanced degenerative discogenic leg pain, with or without low back pain, including those with moderate to severe disc degeneration. In this 2006 study published in the journal, Pain Medicine patients underwent bi-weekly disc space injections of a solution consisting of 50% dextrose and 0.25% bupivacaine in the affected disc(s). Each patient was injected an average of 3.5 times. Overall, 43.4% of patients achieved sustained improvement as shown by average changes in numeric pain scores of 71% between pretreatment and 18-month measurements. The authors concluded that intradiscal injection of hypertonic dextrose has promise as a treatment for managing the pain of advanced lumbar disc degeneration.

Research:

In a retrospective case series of 21 patients (31) with MRI-confirmed lumbar disc degeneration and refractory low back pain/non-radicular low back pain, 18 (86%) of patients experienced 70% or greater improvements in pain and function at 1-year follow up. Patients underwent 3 Prolotherapy treatment sessions at 1–3 weeks apart, which included injections at the ligamento-periosteal junctions at the origin and insertion of the posterior sacroiliac ligaments, iliolumbar ligaments, facet joint capsules, and supraspinous and interspinous ligaments (all bilaterally). Injections were done under fluoroscopic guidance.

Research:

A small case series of 4 patients (32) with low back pain also proved successful in treating those with disc herniations with Prolotherapy. Patients underwent 3–9 Prolotherapy sessions to the ligaments of the low back (almost all 1 month apart) with all patients experiencing 95–100% pain relief and increase in function, including the ability to return to work.

A June 2021 study in the British Medical Bulletin (36) reviewed the available research on Prolotherapy for low back pain and suggested: “Considering the level of evidence and the quality of the studies assessed . . .Prolotherapy is an effective management modality for chronic low back pain patients in whom conservative therapies failed.”

Research:

Research from the University of Manitoba published in The Journal of Alternative and Complementary Medicine (65)  This study suggests that Prolotherapy using a variety of proliferants can be an effective treatment for low back pain from presumed ligamentous dysfunction for some patients when performed by a skilled practitioner

Sacroiliac joint-mediated pain

Research:

In a study published in the British Journal of Sports Medicine, (57) doctors found positive clinical outcomes for 76% of patients treated with Prolotherapy suffering from sacroiliac joint problems.  In this study, 3 injections at 6-week intervals of a hypertonic dextrose solution were given into the dorsal interosseous ligament of the affected sacroiliac joint of each patient.

A 2010 paper published in The Journal of Alternative and Complementary Medicine (58) compared the pain relief effects of Prolotherapy to corticosteroid injection. At 15 months, 58% of the patients treated with Prolotherapy reported that more than half of their pain was relieved, which was statistically significant compared with only 10% in the corticosteroid group who reported that same level of pain relief. The researchers here concluded: “Intra-articular Prolotherapy provided significant relief of sacroiliac joint pain, and its effects lasted longer than those of steroid injections. Further studies are needed to confirm the safety of the procedure and to validate an appropriate injection protocol.”

In a December 2019 study, (59) doctors made these observations concerning Prolotherapy and Platelet Rich Plasma (PRP) Injections. Platelet Rich Plasma (PRP) Injections are considered a type of Prolotherapy when applied in a similar manner as explained above.

SI joint pain can be generated from extra-articular elements including ligaments and capsules. (The SI joint pain does not necessarily have to come from the joint itself). Prolotherapy involves the injection into the area where repairing and strengthening are thought to be needed. The application of Prolotherapy for SI joint pain consists of making injections in the periarticular and intra-articular areas to treat pain and sacral ligament laxity. Some studies reported the positive clinical outcomes of Prolotherapy for SI joint pain and even a superior effect and longer duration for relief of SI joint pain compared to the injection of a steroid into the joint.

An earlier study in the Journal of Spine Disorders  (60) demonstrated that for patients with chronic low back pain who had failed to respond to previous conservative care Prolotherapy could be an effective treatment. Patients were randomly assigned to receive a double-blind series of 6 injections at weekly intervals of either a xylocaine/proliferant or a xylocaine/saline solution into the posterior sacroiliac and interspinous ligaments, fascia, and joint capsules of the lower back from L4 to the sacrum. Of the 39 patients assigned to the proliferant group, 30 achieved a 50% or greater reduction in both pain and disability scores at 6 months compared with 21 of 40 in the group receiving the saline solution. The proliferant group also achieved greater improvements on the visual analog, pain, and disability scales.

In a 2004 audit of conservative treatments for low back pain, patients who were diagnosed with sacroiliac pain via diagnostic block were treated either by corticosteroid injection to the sacroiliac joint or by Prolotherapy to the sacroiliac ligaments. Long-term improvement was assessed at 6 months, after which 63% of the Prolotherapy group reported a substantial drop in pain severity compared with only 33% in the corticosteroid group.

A December 2021 paper in the Journal of Back and Musculoskeletal Rehabilitation performed Prolotherapy on six hundred fifty-four patients with chronic low back pain and lumbar disc herniation at four to six-week intervals. The results were:

The Visual Analogue Scale (0-10 0 = no pain 10 = severe, unbearable pain) scores decreased from very severe pain of 7.2  to a mild to almost no pain score of 0.9 after 52 weeks of the treatment. Thirty-four patients’ treatments resulted in poor clinical results (5.2%), and 620 of the patients’ pain improved (94.8%).

Conclusion: “Prolotherapy can be regarded as a safe way of providing a meaningful improvement in pain and musculoskeletal function compared to the initial status. The diagnostic injection is an easy way to eliminate patients and may become a favorite treatment modality. 5% dextrose is a more simple and painless solution for Prolotherapy and also has a high success.”

Prolotherapy for patients with long-term and often severe low back pain and disability having failed physical therapy and chiropractic.

In research published in the journal International Musculoskeletal Medicine (66), doctors explored the use of Prolotherapy in patients who had failed to respond to conservative approaches including spinal manipulation and physiotherapy. These patients had longstanding and often severe pain and disability. Utilizing only treatments that included 3 injections over a 3 to 5 week period, they confirmed that 91% of respondents were better or not worse off after 12 months.

An April 2021 review article (9) published in the British Medical Bulletin examined previously reported studies on Prolotherapy patient outcomes in the treatment of chronic low back pain. The researchers combined data from 12 studies. The general conclusion was “Prolotherapy is an effective management modality for chronic low back pain in patients in whom conservative therapies failed.”

Prolotherapy for failed back surgery syndrome

A July 2019 study in the European Spine Journal (10) suggested that “dextrose (Prolotherapy) is one of the regenerative methods that has gained popularity in the treatment of many musculoskeletal problems, and (the researchers)  aimed to present and evaluate the outcomes of 5% dextrose (Prolotherapy) for the treatment of failed back surgery syndrome.”

Study summary:

Results: There was a statistically significant difference between repeated VAS and ODI measurements.

Conclusions: These results may be the first step giving a lead to an undiscovered field. This treatment method should be kept in mind for failed back surgery syndrome patients before giving a decision of revision surgery. ”

Prolotherapy for Shoulder Pain

A November 2020 study in the Journal of Back and Musculoskeletal Rehabilitation (33) accessed the effectiveness of Prolotherapy in shoulder disorders. To do this the researchers evaluated existing studies to see if they could form a consensus on how effective, or not effective Prolotherapy can be.

Here are the summary learning points:

The researchers suggested: “Prolotherapy (appears) to be a safe treatment option with perhaps greater efficacy for shoulder pathology when provided through a series of injections using higher concentrations of dextrose.”

A June 2021 paper (34) found that hypertonic dextrose (Prolotherapy) infiltrations reduced pain in individuals with rotator cuffs in the long term. Hypertonic dextrose infiltrations could be an alternative to non-invasive treatments when no favorable results can be achieved. However, due to the small number of studies included in this meta-analysis, new studies are necessary to clarify the efficacy and safety of this intervention.

Comparing one Prolotherapy treatment vs One Cortisone Injection

A March 2021 study in the journal Advanced Biomedical Research (35) compared the effectiveness of Prolotherapy injections with corticosteroid injection in patients with rotator cuff dysfunction. The researchers concluded: “Both ultrasound-guided dextrose Prolotherapy and cortisone injections are effective in the management of rotator cuff-related shoulder pain in both short-term and long-term with neither being superior to the other. Therefore, Prolotherapy may be a safe alternative therapy instead of corticosteroid injection due to the lack of its side effects.” One item to note is that we typically do not find Prolotherapy to be a one-time treatment. We see its maximum benefit in three to six treatments.

Doctors at Taipei Medical University published a February 2022 study in the Archives of Physical Medicine and Rehabilitation (62) on the effects of Prolotherapy on pain and shoulder disability in patients with chronic supraspinatus tendinosis. The concluded Hypertonic dextrose Prolotherapy injection could provide short-term pain and disability relief in patients with chronic supraspinatus tendinosis. Ultrasound imaging at week 6 revealed changed tendon morphology.

The review of this study revealed familiar findings. Prolotherapy treatment can help BUT prolotherapy treatment will not be as successful if it is one shot one time, the initial success of pain relief and better range of motion and function can be sustained if further treatments are initiated.

Published research papers from our doctors at Caring Medical on Shoulder Disorders


In this video, a general demonstration of Prolotherapy and PRP treatment is given for a patient with repeated shoulder dislocations

Danielle R. Steilen-Matias, MMS, PA-C narrates the video and is the practitioner giving the treatment:


Prolotherapy for Cervical Spine Instability and related symptoms

This section will also provide information on the following symptoms as they relate to neck pain and cervical spine instability

The Horrific Progression of Neck Degeneration with Unresolved Cervical Instability. Cervical instability is a progressive disorder causing a normal lordotic curve to end up as an “S” or “Snake” curve with crippling degeneration.
The Horrific Progression of Neck Degeneration with Unresolved Cervical Instability. Cervical instability is a progressive disorder causing a normal lordotic curve to end up as an “S” or “Snake” curve with crippling degeneration.

Since 1993, Ross Hauser, MD and Marion Hauser, MS, RD have developed Caring Medical into one of the world’s leading clinics for Prolotherapy (including dextrose, PRP, and stem cells) with a commitment to helping the toughest chronic pain cases. ​Today, our work is heavily focused on the cervical spine.

Published research papers from our doctors at Caring Medical on Cervical Spine Instability and related symptoms

Degenerative Disc Disease in the Cervical Spine

Ross Hauser, MD. Cause of occipital neuralgia and migraines as seen on DMX and resolved with Prolotherapy

In this video, Ross Hauser, MD offers a brief introduction to causes of occipital neuralgia and migraines and is treated with the aid of DMX (Digital Motion X-Ray and simple dextrose Prolotherapy cervical spine injections.

Prolotherapy and Whiplash Associated Disorders

A September 2020 study in the journal Regenerative Medicine (44) presented successful treatment of severe, longstanding, treatment-resistant Whiplash-Associated Disorders with Prolotherapy.

Learning points

Patient outcomes and case histories following Prolotherapy injections for whiplash have a decades-long history. George Hackett MD, a pioneer in the treatment of Prolotherapy published findings in 1960 (45) and 1962 (46). In these papers, Dr. Hackett and his colleagues reported treating patients with whiplash injuries and noted more than 85% of patients had cervical ligament injury-related symptoms, including those with headache or whiplash associated disorder These patients upon completion of treatment reported they had minor to no residual pain or related symptoms after Prolotherapy. In a 1963 study published in the medical journal Headache (47) Dr. Hackett was a co-author on this paper led by Daniel Kayfetz DO. In this study, 206 patients were treated with Prolotherapy for their whiplash-related headaches. Outcome results showed that in 79% of patients, prolotherapy completely relieved their headaches.

This is also confirmed in our own published research spearheaded by Danielle R. Steilen-Matias, PA-C. In this research that appeared in The Open Orthopaedics Journalwe showed that conventional treatments for chronic neck pain remain debatable, primarily because most treatments have had limited success because they did not address the cervical ligaments. In our study, we were able to conclude and document Prolotherapy injections to be an effective treatment for chronic neck pain and cervical instability due to whiplash, especially when due to ligament laxity in the cervical joints. (48)

Prolotherapy for hip pain


Published research papers from our doctor at Caring Medical on Hip Disorders

In the Journal of Prolotherapy, we sought to show how Prolotherapy could provide high levels of patient outcome satisfaction while avoiding hip surgery. Here is what we reported:

Patients have contacted an average of 19 months following their last Prolotherapy session and asked questions regarding their levels of pain, physical and psychological symptoms, and activities of daily living, before and after their last Prolotherapy treatment.

Results: In these 94 hips,

The results confirm that Prolotherapy is a treatment that should be highly considered for people suffering from chronic hip pain.

Published research on Prolotherapy:

Dr. Ross Hauser and our team have published a number of research papers, case studies, and scientific editorials in the Journal of Prolotherapy, including articles on Prolotherapy as an alternative to surgery; Prolotherapy for chronic back pain; cartilage regeneration in knees; Stem cell therapy for degenerative joint disease; Prolotherapy as for meniscus tears, and many, many more.

Dysplasia of the hip

A February 2020 study  (56) looked at patients who developed osteoarthritis as a result of developmental dysplasia of the hip, (the socket of the hip joint being too shallow) and treated some patients with Prolotherapy and others with an exercise program.

The study concluded: “Prolotherapy could provide significant improvement for clinical outcomes in developmental dysplasia of the hip and might delay surgery.

Prolotherapy for Medial tibial stress syndrome – shin splints

A study published in the Journal of Foot and Ankle Research (37) examined the effectiveness of Prolotherapy injections in difficult to treat and chronic Medial tibial stress syndrome. In this study sports active people were treated and followed to see how many returned to sports and at what level.

Conclusions: “Ultrasound-guided 15% dextrose Prolotherapy injection has a significant medium-term effect on pain in Medial tibial stress syndrome. This benefit may be maintained long-term; however, more robust trials are required to validate these findings. . . Clinicians should consider the use of ultrasound-guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant Medial tibial stress syndrome.”

More research on possible patient outcomes using Prolotherapy for shin splints can be found here: When you have chronic and painful shin splints and nothing helped

Adductor-related groin pain syndrome

A March 2021 review study (38) looked at research outcomes for the treatment of Adductor-related groin pain. They found that the intervention(s) showing the greater level of strength of evidence, and the greater grade of recommendation are compression clothing therapy, manual therapy and strengthening exercise, and prolotherapy.”

Prolotherapy for TMJ related pain

The research on Prolotherapy for Temporomandibular Joint Pain and Dysfunction


Comprehensive Prolotherapy for TMJ. 

In this section, we will discuss how to turn a degenerative TMJ environment into a healing environment through the use of Comprehensive Prolotherapy.

“Dextrose prolotherapy is one of the most promising approaches in the management of TMD”

A March 2021 study in the Journal of Maxillofacial and Oral Surgery (11) writes: (This) study concluded that Prolotherapy is an effective therapeutic modality that reduces TMJ pain, improves joint stability and range of motion in a majority of patients. It can be a first-line treatment option as it is safe, economical and an easy procedure associated with minimal morbidity.”

In March 2019, publishing in the journal Mayo Clinic Proceedings (12)  doctors from the University of British Columbia, University of Missouri-Kansas City, School of Medicine, the University of Wisconsin School of Medicine and Public Health, and the Chinese University of Hong Kong announced these findings in their study to assess the LONG-TERM effectiveness of dextrose Prolotherapy injections in study participants with temporomandibular dysfunction. Their results: “Intraarticular (Prolotherapy) resulted in clinically important and statistically significant improvement in pain and dysfunction at 12 months compared to lidocaine injection.”

Indian doctors writing in the Journal of Maxillofacial and Oral Surgery (13found positive results utilizing Prolotherapy injections for TMJ in recent research (June 2017). Here is what they said: In their study, the researchers examined 23 patients suffering from either chronic recurrent dislocation or subluxation of the TMJ who were treated with the single-injection technique Prolotherapy with 25 % dextrose into the pericapsular tissues along with auriculotemporal nerve block.

Prolotherapy reports on TMJ disc dislocation

In Prolotherapy research, doctors say that they see appreciable improvements in the number of episodes of dislocation and clicking after Prolotherapy treatment.

Prolotherapy and aspiration (arthrocentesis) provided significant relief for TMJ patients.

Doctors at Ordu University in Turkey published in The Journal of Alternative and Complementary Medicine (15) suggesting that Prolotherapy and aspiration (Arthrocentesis) provided significant relief for TMJ patients.

A December 2020 study in the medical journal Cranio, Journal of Craniomandibular Practice (16) also compared the effectiveness of dextrose Prolotherapy in conjunction with arthrocentesis (fluid draining of the TMJ) and dextrose prolotherapy alone in the management of symptomatic TMJ hypermobility. The study concluded Prolotherapy is effective in the management of TMJ hypermobility. However, Prolotherapy with arthrocentesis may be superior to Prolotherapy alone in the management of TMJ hypermobility.

March 2021 paper in the journal Head and Face Medicine (39) examined and treated Forty adolescents and young adults, aged 16 to 30 years old, with distinct combination of symptoms of TMJ “closed lock.” Patients received anesthetic blockages of the auriculotemporal nerve, then performed mandibular condylar movement exercise for 10 min, and subsequently received hypertonic dextrose Prolotherapy in retro-discal area of TMJ. Clinical assessments at baseline and at follow-up (2 weeks, 2 months, 6 months, and 5 years) included intensity and frequency of TMJ pain, mandibular range of motion, TMJ sounds, and impairment of chewing. Conclusions: “The technique combining mandibular condylar movement exercise with an auriculotemporal nerve block and dextrose Prolotherapy is straightforward to perform, inexpensive and satisfactory to young patients with TMJ closed lock.”

A July 2018 paper in the Journal of Oral Rehabilitation compared Prolotherapy to Placebo injections. The researchers found: “Within the limitations of the study, dextrose Prolotherapy may cause significant reduction in mouth opening and pain associated with TMJ hypermobility. Conclusions with regard to the reduction of episodes of subluxation/dislocation cannot be drawn. ” In their study that could not give good evidence that TMJ subluxations or dislocations were reduced. (43)

A February 2022 paper in the journal Oral and Maxillofacial Surgery Clinics of North America (63) found “Prolotherapy with hypertonic glucose is effective for treating hypermobility and subluxation of the temporomandibular joint.”

Prolotherapy for Elbow Pain

Research: Prolotherapy superior to cortisone injections

A November 2019 study in the journal Orthopedic Research and Reviews (41) compared the effectiveness of Prolotherapy to corticosteroid injections. “This investigation showed that both corticosteroid injection and dextrose Prolotherapy efficiently improved pain and function in patients with chronic lateral epicondylitis. In the Prolotherapy group, this improvement persisted even after 1-month follow-up and the results after one injection were still improvable, whereas, in the parallel-group, steroids only provided a short-term improvement. This finding proved that dextrose Prolotherapy had better and longer effects in treating chronic tennis elbow.”

Prolotherapy compared to Hyaluronic acid injection

September 2020 study in The Journal of Alternative and Complementary Medicine, (42) compared the effects of hyaluronic acid and dextrose Prolotherapy injections in patients with chronic lateral epicondylalgia. Hyaluronic acid injection and Prolotherapy injections were both effective in reducing pain and increasing grip strength and function in patients with chronic lateral epicondylalgia. Prolotherapy injection was more effective in the short term than Hyaluronic acid injection, in terms of pain relief and functional outcome.

A January 2022 paper (50) published in the journal Arthroscopy found “Dextrose Prolotherapy and extracorporeal shock wave therapy (ESWT) were the best two treatment options for pain control and extracorporeal shock wave therapy was the best treatment option for grip strength recovery. Corticosteroids were not recommended for the treatment of lateral epicondylitis. More evidence is required to confirm the superiority in pain control of Dextrose Prolotherapy among all these treatment options on lateral epicondylitis.”

Prolotherapy against corticosteroid injections for the treatment of carpal tunnel syndrome

A July 2022 paper in the journal Pain Management (71) issued an assessment of the effectiveness of ultrasound-guided dextrose prolotherapy against corticosteroid injections for the treatment of carpal tunnel syndrome. Conclusion: Dextrose 5% has similar efficacy as triamcinolone for improving pain intensity, functional limitation in daily life, electrophysiologic parameters and ultrasonographic outcomes.

22 Babaei-Ghazani A, Moradnia S, Azar M, Forogh B, Ahadi T, Chaibakhsh S, Khodabandeh M, Eftekharsadat B. Ultrasound-guided 5% dextrose prolotherapy versus corticosteroid injection in carpal tunnel syndrome: a randomized, controlled clinical trial. Pain Manag. 2022 Jul 18. doi: 10.2217/pmt-2022-0018. Epub ahead of print. PMID: 35848821.

Prolotherapy for chronic plantar fasciitis

A study from 2021 published in the journal Foot and Ankle Specialist (40) compared one injection of cortisone and one injection of dextrose.

A February 2022 study in The Journal of Foot and Ankle Surgery (64) compared the effectiveness of extracorporeal shockwave therapy (ESWT) versus dextrose Prolotherapy on pain and foot functions in patients with chronic plantar fasciitis.

Results of three ESWT sessions versus three single injections of dextrose:

Prolotherapy for myofascial pain syndrome

A September 2020 study (55) evaluated the effectiveness of targeted ultrasound-guided dextrose injection for localized myofascial pain syndrome. In this study, 45 patients with myofascial pain syndrome were non-responsive to alternative treatments with targeted ultrasound-guided dextrose injection. Pretreatment symptom severity and symptomatic response 1 month after treatment were statistically analyzed using a visual analog scale (VAS)-based scoring system.

Conclusion: Targeted ultrasound-guided dextrose injection was remarkably effective for refractory localized myofascial pain syndrome, significantly reducing symptom intensities in the majority of treated patients within one month after a single injection.

Our Prolotherapy research papers, case studies, & scientific editorials:


Prolotherapy Side effects and risks

Prolotherapy Side effects and risks

Because Prolotherapy causes inflammation, the person will often note some bruising, pain, stiffness and swelling in the area after receiving Prolotherapy. Typically this lasts 1 to 7 days. On rare occasions, it lasts longer. Lasting longer is not necessarily bad, some people just inflame more easily. Since the treatment works by inflammation, lingering pain after Prolotherapy can be a sign of healing. If the pain is severe after Prolotherapy, then call the office where the Prolotherapy was done. Prolotherapy should not cause excessive, severe pain. Severe pain after Prolotherapy, especially accompanied by a fever, could indicate an infection. Infection after Prolotherapy is the most serious risk that we have seen.

The risk of infection after Prolotherapy is between 1 and 1000 to 1 and 10,000 procedures. The most common infection with Prolotherapy is an infection in the skin. This type of infection typically responds to an antibiotic taken by mouth. If a joint or blood infection results, then intravenous antibiotics will typically be needed for six weeks.

Since some of the risks with Prolotherapy relate to the actual technique or solutions used, it is important to go to a clinic with a lot of experience and one who has researched the best options for various types of pain, versus just utilizing the same ingredients for every patient.

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 This page was updated May 9, 2022

 

 

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