Prolotherapy: A Minimally Invasive Option for Musculoskeletal Pain

written for Marin Medical Society Magazine, Summer 2014

Haven’t we all had the experience of seeing one of our most loyal patients return again and again with the same complaint of musculoskeletal pain? She has tried physical therapy, NSAIDs, cortisone and may have even had surgery. And the pain is still there. We’ve watched her weight increase and her function decrease. The fact is, we feel helpless because we have run out of ideas. Perhaps you may have faced this scenario countless times.

Definition: Enter Prolotherapy. Prolotherapy is short for Proliferative therapy which is the injection of an irritant solution into the tendons and ligaments surrounding a painful joint. This solution causes the patient to mount a localized inflammatory response which initiates the healing cascade. From this cascade, there is cellular proliferation and collagen production(1) The resulting soft tissue is then able to regain it’s function of stabilizing the joint. The mildest inflammatory agent used is 15% Dextrose, and depending on the severity of the disease, 25% Dextrose or Platelet-Rich-Plasma (PRP) may be used. These are different substances and are not interchangeable.

Procedure: The Procedure entails a careful examination of the patient, followed by mapping out the structures of the joint. For instance in the knee, the prolotherapist will draw the patella, the joint, the collateral ligaments, etc… and then inject lidocaine into the skin, superficial to these structures. This is followed by the injection of the proliferant solution into the damaged soft tissue and intra-articularly. Prolotherapists are keeping in mind that although the pain may be in one area, the laxity may very well lie in a separate part of the joint, which must be addressed as well.

In PRP, the patient’s own blood is drawn and spun down to collect only the supernatant which contains platelets and growth factors. This is injected back into the diseased area.

Patient Response: The patient will mount an inflammatory response within 3-10 days, followed by a reparative phase, lasting 2-4 weeks, and then a remodeling phase from 4-6 weeks. It is by 4-6 weeks that the patient will know if this has helped. The number of treatments required for the patient varies. Typically, it is three. Each time the patient returns they report less and less pain. In some cases, one treatment is all that is needed.  In other cases, multiple treatments are necessary. But once the pain comes down, it does not return unless the patient is overactive. It is hard to gage exactly how effective Prolotherapy can be, but in general it works about 75% of the time.

Adjunctive Treatment: Prolotherapy is best done in association with an exercise regimen, for instance, gentle core strengthening for back issues or upper leg strengthening for knee issues. If the patient remains weak, they are very likely to reinjure themselves.

Cautions: Prolotherapy is not done first line when there is an obvious surgical indication, but can work well as an adjuvant treatment to surgery. And Prolotherapy is not indicated as a treatment for acute injury.

Side Effects: While Prolotherapy is very safe, the usual cautions apply as they would to any injection (ie potential infection and bleeding). Due to the possibility of hematoma formation or internal bleeding, anticoagulants and coagulopathies are the only real contraindication to the deep injections in the spine. Pneumothorax is a potential complication of injections done in the area of the thoracic spine and ribs. And rare CVAs have been reported with cervical injections. In the Lumbar spine there is obvious risk of an inadvertent lumbar puncture, but intrathecal dextrose is safe and without neurologic effect. Nerve injury is a slight possibility, but the potential for long -term neurologic damage is negligible. In the hands of a well  trained and conscientious physician, the risk of any of the above is extremely low. Since the small amount of dextrose injected does not raise blood sugar, diabetes is not a contraindication, nor does it require blood sugar monitoring.

Indications: Proliferative Therapy works well for pain caused by early Osteoarthritis and any other autoimmune arthropathies. PRP can often be helpful in patients with more significant OA.  In a recent study by the Clinical Journal of Sports Medicine, (3), there was decreased pain and stiffness and increased function in arthritic knees treated with PRP. In this same study, MRIs were compared before and one year after treatment with PRP, where there was no change in the appearance of the osteoarthritis, in contrast to the usual 4-7% decline in cartilage volume normally seen in knee arthritis. Of course, in clinical practice, we do not use MRIs to follow the progress of our intervention of proliferative therapy. A recent review published in the Archives of Physical Medicine and Rehabilitation, (2) fount that PRP was an effective treatment of degenerative knee joint cartilage.

Joint Laxity (used here to indicate the wear and tear on soft tissue around the joint leading to excessive motion, frequently after injury, or overuse) and Hypermobility Syndrome are absolute indications for Prolotherapy! During the Reparative Phase of healing, the collagen fibers shrink down to make the soft tissues short and tight. Subtle ligament laxity is present in aging and often occurs after injury. These can be difficult to diagnose but are very important to consider. Hypermobility syndrome is due to structurally weak collagen rendering the joint support inadequate.  Hypermobility Syndrome is diagnosed in less than 10% of cases and it occurs in 4-13% of the population. This often leads to chronic pain and is now recognized as one of the causes of fibromyalgia and chronic pain syndrome. Additionally, the NIH is recognizing hypermobility as one of the causes of pain in osteoarthritis.

Hypermobility syndrome can be diagnosed using the Beighton Score within the Brighton Criteria . Scoring: 1 point per criterion, if they could do these maneuvers at any time during their lives. Score >4 = Major Criteria for Hypermobility,

1) Lumbar flexion with hands to the ground (One point for each side)

2) Elbow hyperextension

3) Knee hyperextension

4) Wrist flexion (thumb touches wrist in flexion)

5) Fifth finger hyperextension

Specific indications for Prolotherapy in a patient with hypermobility is pain in a hypermobile joint that has not responded to usual care. So a very short list of areas that benefit from proliferative treatment include: proximal interphalangeal pain, recalcitrant tennis elbow, anterior instability of the shoulder, sacro-iliac instability, lumbar, thoracic, and cervical instability, patellar hypermobility, and chronically spraining ankles that are lax in inversion. Prolotherapy should be considered with in any painful syndrome with a hypermobile  joint.

Radiculopathy in the presence of a normal MRI and Nerve Testing are indications for Prolotherapy. Many times the patient has referred pain, but there is no objective clinical evidence (normal neurologic exam) and a normal MRI and nerve tests. In their book, “ Ligament and Tendon Relaxation Treated by Prolotherapy”, physicians Hackett, Hemwall and Montgomery elucidate reproduceable referral patterns of tendon and ligament dysfunction. What had been thought to be radiculopathy in the leg may very well be ligamentous laxity in the pelvis. This is easily diagnosed by injection of a milligram of lidocaine into the area in question, in order to resolve the referred pain. In the event that the referral pattern resolves in that moment, then it is very likely instability and will respond to Prolotherapy.

Dextrose Prolotherapy has used and it’s effectiveness studied for the following conditions.

1-Sacro-Iliac Joint Pain: Dextrose Injection is more effective than Steroidal injections treating chronic SI joint pain(9)

2-Chronic Low Back Pain: Both Dextrose and Saline injections result in sustainable and significant improvements in pain disability in chronic low back pain patients (7)

3-Groin Pain: Dextrose Prolotherapy resulted in higher full sport return in patients who had failed conservative treatment compared with every other therapy study and as much as surgical options (11)

4-Knee Osteoarthritis: Dextrose injection resulted in substantial long-term functional improvement (twice the MCID) (10)

5-ACL Laxity: Dextrose intra-articular injections improved pain, swelling and laxity by objective machine measurements progressively to 36 months with KT- 100 documented laxity (6)

6-Achilles Tendonosis: Dextrose Prolotherapy resulted in impressive pain reduction accompanied by objective changes in  unblinded ultrasound measurements(4)

7-Coccygeal Pain: Dextrose injection into the coccyx for persistent pain after coccygeal fracture (5)

8-Plantar Fasciitis

9-Posterior Tibial Tendonitis

Unfortunately, Proliferative Therapy is generally not a covered benefit from most insurance companies, nor is it covered by Medicare.

Conclusion: Prolotherapy is a valuable tool for relieving and often eliminating difficult pain problems. In my practice I have seen Prolotherapy bring major change into the lives of my patients, which is especially satisfying when they are similar to our patient in the beginning of this article. More than anything else, I have something useful to offer and I don’t feel helpless any more.

You may already have patients in mind that would benefit, but if you want help considering the best options for your pain patients, I would be happy to speak with you.

Gloria Tucker MD is a Diplomat of the American Board of Sports Medicine is an Instructor of Proliferative Therapy with the Hackett Hemwall Foundation and Practices in Novato, California  and Santa Rosa, California at, (415) 898-6888

Pain, Tight Tendons and Loose Ligaments
written for Pain Treatment Directory

Hello my patients and friends,As a doctor of Musculoskeletal Medicine, it is one of my goals in life to get people out of pain! And I love to teach both patients and doctors about what is really going on with the pain in our bodies. With that aim in mind, let’s begin by understanding the true source of most pain that is not addressed by traditional medicine. This often includes the vague, frustrating diagnosis of Fibromyalgia.

To get started we need to know some anatomy:

Ligaments: Hold bone to bone.

Tendons: Hold muscles to bones

Joints: Space between 2 bones, allowing motion of the bones.

The source of the pain around the bones and muscles is actually that the tendons are too tight, or the ligaments are too loose or both.


How do ligaments become too loose?  Ligaments are fibers (made up of Elastin and Collagen) which have a certain amount of stretch and a certain amount of tightness.  In every joint, the ligaments hold the joint in place allowing it to move the bones in the proper direction. We know abnormal movement in the joint is a very common source of arthritis. So the ligaments keep the joints from moving too much. In the knee joint, for instance, along each side is a ligament preventing the knee from going inward or outward when we walk.

Ligaments become too loose by:

1) Aging and Overuse: By far the most common. The ligaments start out as supple fibers and with the drying process (that accompanies aging and overuse) become similar to a frayed rope. As a result, they don’t hold the bones together as well.

2) Injury: Think of skiing where every leg is for itself and the lower leg is going sideways on the upper leg. This can stretch the side ligaments and sometimes result in small tears (degeneration) that don’t heal, leaving a person with a chronically unstable joint.

3) Genetics: Hypermobility: Some people have a different sort of collagen which results in too much motion in the ligament. This is not uncommon and is extremely underdiagnosed.  Interestingly, being able to bend excessively it may be just a fun party trick until there is an injury and then the total body hypermobility announces itself. In this situation, people are unable to strengthen because their bones move out of place (which they are often unaware) and it hurts! When it is very significant it is called Ehlers- Danlos Syndrome.

4) Infection/ Certain Drugs: Rarely, an infection or certain drugs can cause weakness in the ligaments and tendons.

Why are Loose Ligaments painful? Because the bones will move too much. Many times, most people don’t even realize what is happening.

Then what happens? The body is amazing! It will compensate by tightening the tendons, in an attempt to keep us straight. Over time, with the tendons constantly contracted, the muscles become weak and painful in the region of the insertion into the bone, because they are always holding tight. So often times we have pain  and tight “muscles” in a place that is not the source of the problem, and this can be very confusing.

How do we strengthen ligaments?  The only way to strengthen ligaments is through PRP or dextrose prolotherapy.  By making very precise injections of these safe substances directly into the problem ligament, we can strengthen them and return the patient to pain-free activity.  This treatment promotes the body to heal those specific areas by its own natural process.

Tight Tendons:

We have discussed one source of tightness which is chronic contraction to counteract the loose ligaments. The other source of tightness is overloading the muscles. We all know what it feels like to have sore muscles after a heavy work out. This is not what I am referring to. This is, day after day, overusing the muscles so the tendons which hold the muscles begin to take the brunt of the problem and become chronically sore. So the pain will not be in the muscles, but at the attachment of the muscles next to the bones.

Wrong approach: Trying to strengthen the muscles. This won’t work because they are already on overload.  This can be very frustrating because now the muscles are getting weak.

Better approach: Rest the muscles.  This actually works, along with gentle strengthening as the tendon relaxes.  However, this can take a very long time and as a result, the muscle gets even weaker and so the rehabilitation is very slow.

Best approach: Treat the tendon with Prolotherapy/PRP followed by gentle strengthening.  This stimulates the body to heal the tendons naturally.

Worst approach: Treating the tendon with steroids which weakens and degenerates the tendon.

Do you or someone you know have mysterious pain, or “fibromyalgia”? This is frequently treatable with PRP or Dextrose Prolotherapy in the right hands. Stay tuned.  In my upcoming blogs, we will address these pain syndromes, and the sane, effective path to healing. I hope you will come with me on this journey.

PS-using serious sterile precautions, we are open for consultations and treatment.




1) Brian Halpern, Salma Chaudhury, Scott A. Rodeo, Catherine Hayter, Eric Bogner, Hollis G. Potter, Joseph Nguyen. Clinical and MRI Outcomes After Platelet-Rich Plasma Treatment for Knee Osteoarthritis. Clinical Journal of Sport Medicine, 2012; 1 DOI: 10.1097/JSM.0b013e31827c3846

2) Chang KV, Hung CY, Aliwarga F, Wang TG, Han DS, Chen WS.Comparative Effectiveness of Platelet-Rich Plasma Injections for Treating Knee Joint Cartilage Degenerative Pathology: A Systematic Review and Meta-Analysis.Archives of Phys. Med. Rehabil, 2014 March;95(3);562-575.doi; 10.1016/j.apmr.2013.11.006. Epub 2013 Nov 27

3) Cusi M; Saunders J; Hungerford B; Wisbey-Roth T; Lucas P; Wilson S. The use of prolotherapy in the sacroiliac joint. Br J Sports Med 2010;44: 100-104.

4) Freeman JW, Empson YM, Ekwueme EC, Paynter DM, Brolinson PG. Effect of Prolotherapy on Cellular Proliferation and  Collagen Deposition in MC3T3-E1 and Patellar Tendon Fibroblast Populations. Transl Res. 2011 Sep;158(3):132-9.doi: 10.1016/j.trsl.2011.02.008. Epub 2011 Mar 21.

5) Gosens T, Peerbooms JC, van Laar W, den Oudsten BL.  Ongoing Positive Effect of Platelet-Rich Plasma Versus Corticosteroid Injection in Lateral Epicondylitis: A Double-Blind Randomized Controlled Trial With 2-year Follow-up [In Process Citation] Am J Sports Med  (United States), Jun 2011, 39(6) p1200-8.

6) Hackett GS, Hemwall GA, Montgomery GA : Ligament and Tendon Relaxation treated by Prolotherapy  Charles C Thomas Publisher

7) Khan SA; Kumar A; Varshney MK; Trikha V; Yadav CS: Dextrose prolotherapy for recalcitrant coccygodynia J Orthop Surg, Apr 2008, 16 (1) p27-9

8) Rabago D, Patterson J.Hypertonic Dextrose Injections (prolotherapy)for knee osteoarthritis: A Randomized Controlled Trial.  Annals of Family Medicine May/June 2013 doi: 10.1370 vol.11 no.3 229-237

10) Reeves KD Hassanein K Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity: A prospective and consecutive patient study. Alt Ther Hlth Med May-Jun 2003, 9(3): p58-62.

11) Ryan M, Wong A, Taunton J. Favorable outcomes after sonographically guided intratendinous injection of hyperosmolar dextrose for chronic insertional and midportion achilles tendinosis. Am J Roentgenol. 2010 Apr;194(4):1047-53.

12) Topol GA, Reeves KD: Regenerative injection of elite athletes with career-altering chronic groin pain who fail conservative treatment: a consecutive case series. Am J Phys Med Rehabil 2008;87.

13)  Yelland MJ, Glasziou PP, Bogduk N, et al. Prolotherapy Injections, Saline Injections, and Exercises for Chronic Low-Back Pain: A Randomized Trial. Spine 2004; 29(1): 9-16.)



1) Cusi M, Sanders J. “The Use of Prolotherapy in the Sacroiliac Joint.” British Journal of Sports Medicine

2) Deganais S, Haldemean S, Wooley J. “Intraligamentous Injection of Sclerosing Solution (Prolotherapy) for Spinal Pain: a critical review of the literature.” Spine J 2005

3) Klein Robert G, Patterson Jeffrey. “Prolotherapy for the Treatment of Back Pain.” Position Statement of the American Association of Orthopedic Medicine

4) Rabago D, Slattengren A, Zgierska A. “Prolotherapy in Primary Care Practice.” Primary Care Clinics in Office Practice

5) Reeves K. Dean, Hassanein Khatab. “Randomized Prospective Placebo Controlled Double Blind Study of Dextrose Prolotherapy for Osteoarthritic Thumb and Finger Joints; Evidence of Clinical Efficacy.” Journal of Alternative and Complementary Medicine

6) Reeves KD, Hassanein K. “Randomized Prospective Double Blind Placebo Controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity.” Alternative Therapy Health Medicine

7) Consensus Statement on the Use of Prolotherapy or Musculoskeletal Pain
The purpose of this paper is to explicate the theory, scientific evidence, methods, and applications for the procedure of Prolotherapy in the treatment of musculoskeletal pain. The example of knee osteoarthritis is used as an example as to why Prolotherapy should be used compared to other invasive therapies.

8) Tucker, Gloria – “Prolotherapy for Patients with musculoskeletal pain” – Marin Medicine Summer 2014

9) Local Frontiers – Pg 26-28