Prolotherapy Research and Treatment Guidelines

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

Ross Hauser, MD

Prolotherapy is an in-office injection treatment that research and medical studies have shown to be an effective, trustworthy, reliable alternative to surgical and non-effective conservative care treatments. In our opinion, based on extensive research and clinical results, Prolotherapy is superior to many other treatments in relieving the problems of chronic joint and spine pain and, most importantly, in getting people back to a happy and active lifestyle. This is why it is the Caring Medical treatment method of choice.

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.

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 do we use in our 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 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

Lead 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 an 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 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 dextrosejoint 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:

A May 2021 study in the Journal of clinical orthopaedics and trauma (8) suggests while Prolotherapy researchers may be biased or overlyentusiastic about the treatment, Prolotherapy does offer safe benefit for knee pain. This is what these researchers wrote:

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

Articles for patients looking for options for eventual knee replacement

Chronic knee problems from an active lifestyle, physically demanding work, or sports-related knee injuries

Meniscus tears

Patella / Knee Cap

Knee Ligaments

Knee diagnosis

Meniscus

Pain AFTER knee arthroscopic surgery

Pain AFTER knee replacement

Prolotherapy and PRP (Platelet Rich Plasma) Injections for Knee Pain

Comprehensive Prolotherapy is an injection technique utilizing many healing factors. They can include or be used in conjunction with Dextrose, Blood Platelets, and stem cells. The stem cells and blood platelets are drawn from you the patient. We typically DO NOT offer stem cell therapy for knee pain as a first option. We may offer PRP treatments in conjunction with Prolotherapy at initial treatment visits.

WE OFFER PRP with PROLOTHERAPY. We do not offer PRP as a single injection treatment.

Articles:


Prolotherapy and Stem Cell Therapy for Knee Pain

Bone marrow derived stem cells

We do not offer stem cell therapy to every patient, in fact, we offer this treatment rarely. The treatment is usually offered only in the most advanced cases of knee degenerative disease. The articles below give a comprehensive review of when stem cell therapy will work, when it will not work, and the realistic options of when it should be considered.


Prolotherapy for Back Pain

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

Caring Medical patients are often surprised to learn that Prolotherapy can heal most disc problems in the neck and back. While we talk about Prolotherapy healing joint pain that results from ligament and tendon injuries, most people are unaware that disc problems result from ligament injuries or instability along the spine. Patients with degenerative disc disease, herniated discs, bulging discs, bone on bone, etc can all be healed with Prolotherapy.

Prolotherapy works to stabilize the ligaments of the spine allowing discs to get back into position and can even create space for a person who has lost space due to one or more degenerated discs. In Prolotherapy research from the doctors of Caring Medical, patients with more than four years of unresolved low back pain were shown to have had their pain improved, stiffness, range of motion, and quality of life measures even 12 months subsequent to their last Prolotherapy session.

Latest research

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 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. ”

Back pain by an initial diagnosis

Spondylolisthesis,  Spondylolysis, Spondylisis

Failed back surgery syndrome

Conservative Care Back Pain Options


Prolotherapy for Shoulder Pain

A November 2020 study in the Journal of back and musculoskeletal rehabilitation 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.”

Robinson DM, Eng C, Makovitch S, Rothenberg JB, DeLuca S, Douglas S, Civitarese D, Borg-Stein J. Non-operative orthobiologic use for rotator cuff disorders and glenohumeral osteoarthritis: A systematic review. Journal of Back and Musculoskeletal Rehabilitation. 2020(Preprint):1-6. [Google Scholar]


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


Articles

Rotator Cuff Tears

Shoulder Instability

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

Cervical Spine instability and Whiplash Associated Disorders and Post Concussion Syndrome

Cervical Spine instability and TMJ

Cervical Spine instability and hearing problems

Cervical Spine instability and vision problems

Cervical Spine instability and headaches

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 treated with the aid of DMX (Digital Motion X-Ray and simple dextrose Prolotherapy cervical spine injections.

Cervical spine instability and symptoms of dizziness, fainting, drop attacks, and other neurological symptoms

Cervical spine fusion surgery

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 were 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.

Prolotherapy for Medial tibial stress syndrome – shin splints

A study published in the Journal of foot and ankle research (1) 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

1 Padhiar N, Curtin M, Aweid O, Aweid B, Morrissey D, Chan O, Malliaras P, Crisp T. The effectiveness of PROLOTHERAPY for recalcitrant Medial TIBIAL Stress Syndrome: a prospective consecutive CASE series. Journal of Foot and Ankle Research. 2021 Dec;14(1):1-2. [Google Scholar]

Adductor-related groin pain syndrome

A March 2021 review study (1) 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.”

1 Bisciotti GN, Chamari K, Cena E, Rodriguez Garcia G, Vuckovic Z, Bisciotti A, Bisciotti A, Zini R, Corsini A, Volpi P. The conservative treatment of longstanding adductor-related groin pain syndrome: a critical and systematic review. Biology of Sport. 2021;38(1). [Google Scholar]

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.

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.

References

1 Bae G, Kim S, Lee S, Lee WY, Lim Y. Prolotherapy for the patients with chronic musculoskeletal pain: systematic review and meta-analysis. Anesthesia and Pain Medicine. 2020 Dec 16. [Google Scholar]
2 Bae G, Kim S, Lee S, Lee WY, Lim Y. Prolotherapy for the patients with chronic musculoskeletal pain: systematic review and meta-analysis. Anesthesia and Pain Medicine. 2021 Jan 31;16(1):81. [Google Scholar]
3 Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain. Clinical Medicine Insights Arthritis and Musculoskeletal Disorders. [Google Scholar]
4 Johnston E, Kou Y, Junge J, Chen L, Kochan A, Johnston M, Rabago D. Hypertonic Dextrose Stimulates Chondrogenic Cells to Deposit Collagen and Proliferate. Cartilage. 2021 Jun 10:19476035211014572. [Google Scholar]
5 Shan Sit RW, Keung Wu RW, Rabago D, et al. Efficacy of Intra-Articular Hypertonic Dextrose (Prolotherapy) for Knee Osteoarthritis: A Randomized Controlled Trial. Ann Fam Med. 2020;18(3):235‐242. doi:10.1370/afm.2520 [Google Scholar]
6 Sert AT, Sen EI, Esmaeilzadeh S, Ozcan E. The Effects of Dextrose Prolotherapy in Symptomatic Knee Osteoarthritis: A Randomized Controlled Study. J Altern Complement Med. 2020;26(5):409‐417. doi:10.1089/acm.2019.0335 [Google Scholar]
7 Rabago D, Kansariwala I, Marshall D, Nourani B, Stiffler-Joachim M, Heiderscheit B. Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis: Feasibility, Acceptability, and Patient-Oriented Outcomes in a Pilot-Level Quality Improvement Project. The Journal of Alternative and Complementary Medicine. 2019 Jan 28. [Google Scholar]
8 Wee TC, Neo EJ, Tan YL. Dextrose prolotherapy in knee osteoarthritis: A systematic review and meta-analysis. Journal of Clinical Orthopaedics and Trauma. 2021 May 20. [Google Scholar]
9 Giordano L, Murrell WD, Maffulli N. Prolotherapy for chronic low back pain: a review of literature. Br Med Bull. 2021 Apr 21:ldab004. doi: 10.1093/bmb/ldab004. Epub ahead of print. PMID: 33884404. [Google Scholar]
10 Solmaz İ, Akpancar S, Örsçelik A, Yener-Karasimav Ö, Gül D. Dextrose injections for failed back surgery syndrome: a consecutive case series. European Spine Journal. 2019 Jul;28(7):1610-7. [Google Scholar]
11 Dasukil S, Arora G, Shetty SK, Degala S. Impact of Prolotherapy in TMDs: a quality of life assessment. British Journal of Oral and Maxillofacial Surgery. 2020 Oct 27. [Google Scholar]
12 Louw WF, Reeves KD, Lam SK, Cheng AL, Rabago D. Treatment of temporomandibular dysfunction with hypertonic dextrose injection (prolotherapy): A randomized controlled trial with long-term partial crossover. InMayo Clinic Proceedings 2019 May 1 (Vol. 94, No. 5, pp. 820-832). Elsevier. [Google Scholar]
13 Majumdar SK, Krishna S, Chatterjee A, Chakraborty R, Ansari N. Single Injection Technique Prolotherapy for Hypermobility Disorders of TMJ Using 25 % Dextrose: A Clinical Study. J Maxillofac Oral Surg. 2017 Jun;16(2):226-230. [Google Scholar]
14  Zhou H, Hu K, Ding Y. Modified dextrose prolotherapy for recurrent temporomandibular joint dislocation. Br J Oral Maxillofac Surg. 2014 Jan;52(1):63-6. doi: 10.1016/j.bjoms.2013.08.018. [Google Scholar]
15 Cezairli B, Sivrikaya EC, Omezli MM, Ayranci F, Cezairli NS. Results of Combined, Single-Session Arthrocentesis and Dextrose Prolotherapy for Symptomatic Temporomandibular Joint Syndrome: A Case Series. The Journal of Alternative and Complementary Medicine. 2017 Oct 10. [Google Scholar]
16 Taşkesen F, Cezairli B. Efficacy of prolotherapy and arthrocentesis in management of temporomandibular joint hypermobility. CRANIO®. 2020 Dec 18:1-9. [Google Scholar]

This page was updated June 17, 2021

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