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 orthomedoffice@gmail.com, (415) 898-6888