LOCAL FRONTIERS: Prolotherapy for Patients with Musculoskeletal Pain

Gloria Tucker, MD

Many physicians have had the experience of seeing one of their most loyal patients return again and again with the same complaint of musculoskeletal pain. The patient has tried physical therapy, NSAIDs and cortisone, and may even have had surgery—but the pain is still there. We’ve watched the patient’s weight increase and function decrease. The fact is, we feel helpless because we have run out of ideas.

Definition
Enter prolotherapy, short for proliferative therapy—the injection of an irritant solution into the tendons and ligaments surrounding a painful joint. The solution causes the patient to mount a localized inflammatory response that initiates the healing cascade.¹ The cascade in turn leads to cellular proliferation and collagen production.^2,3 The resulting soft tissue is able to regain its function of stabilizing the joint.⁴

The mildest inflammatory agent used in prolotherapy is 15% dextrose. 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
Administering prolotherapy entails a careful examination of the patient, followed by mapping out the structures of the joint. In the knee, for instance, the prolotherapist will draw the patella, joint, collateral ligaments and other entities and then inject lidocaine into the skin superficial to these structures. This is followed by an injection of proliferant solution into the damaged soft tissue and intra-articularly. Prolotherapists bear 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 that contains platelets and growth factors. The supernatant is then 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 of 4–6 weeks. By 4–6 weeks, the patient will know if prolotherapy has helped. The number of treatments required for each patient varies. Typically, it is three, but in some cases, only one treatment is needed. Once the pain comes down, it does not return unless the patient is overactive. Gauging the efficacy of prolotherapy is difficult, but in my experience it works about 75% of the time.

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

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

Cautions
While prolotherapy is safe, the usual injection cautions apply, such as potential infection and bleeding. Because of the possibility of hematoma formation or internal bleeding, anticoagulants and coagulopathies are the only real contraindication to deep injections in the spine. Injecting in an area with a tumor is contraindicated. Pneumothorax is a potential complication of injections done in the area of the thoracic spine and ribs. Rare cerebrovascular accidents have also been reported with cervical injections.

Potential Side Effects
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 low. Since the small amount of dextrose injected does not raise blood sugar, diabetes is not a contraindication, nor does prolotherapy require blood-sugar monitoring.

Indications
Prolotherapy works well for pain caused by early osteoarthritis and any other autoimmune arthropathies. PRP can often be helpful in patients with more significant osteoarthritis. A recent study found decreased pain and stiffness and increased function in arthritic knees treated with PRP.⁵ In the same study, MRIs were compared before and one year after treatment with PRP. 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. In clinical practice, however, we do not use MRIs to follow the progress of prolotherapy. A recent review also found that PRP was an effective treatment for degenerative knee joint cartilage.⁶

Hypermobility syndrome and joint laxity are also indications for prolotherapy. Hypermobility syndrome is caused by structurally weak collagen rendering the joint support inadequate. The condition can be difficult to diagnose but important to consider. Hypermobility is diagnosed in less than 10% of cases of patients who have this disorder and occurs in 4–13% of the population. The syndrome often leads to chronic pain and is now recognized as one of the causes of fibromyalgia, chronic pain syndrome and osteoarthritic pain. Prolotherapy works for hypermobility syndrome and tissue laxity because the tissues contract during the reparative phase, becoming short and tight, thereby supporting the joint.

Hypermobility syndrome can be diagnosed using the Beighton Score, a test of nine criteria. The scoring is one point per criterion. If patients score four or more, they may have hypermobility. Here are the criteria:
   •   One point if while standing and bending at the waist, the patient can place palms on the ground with legs straight.
   •   One point for each elbow that bends backwards.
   •   One point for each knee that bends backwards.
   •   One point for each thumb that touches the forearm when bent backwards.
   •   One point for each little finger that bends backwards beyond 90 degrees.

Specific indications for prolotherapy in a patient with hypermobility are pain in any hypermobile joint that has not responded to usual care. A short list of areas that benefit from proliferative treatment includes proximal interphalangeal pain; recalcitrant tennis elbow; anterior instability of the shoulder; sacroiliac instability; lumbar, thoracic, and cervical instability; patellar hypermobility; and chronically spraining ankles that are lax in inversion. Prolotherapy should be considered for 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 has normal MRI and nerve tests and no objective clinical evidence of pain (normal neurologic exam). In their book Ligament and Tendon Relaxation Treated by Prolotherapy, Drs. Hackett, Hemwall and Montgomery elucidate reproducible referral patterns of tendon and ligament dysfunction.⁷ What was thought to be radiculopathy in the leg may very well be ligamentous laxity in the pelvis. The laxity 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, the condition is likely instability and may respond to prolotherapy.

Effectiveness
The effectiveness of dextrose prolotherapy has been studied for the following conditions.
Sacroiliac joint pain. Dextrose injection proved more effective than steroidal injections for treating chronic sacroiliac joint pain.⁸
Chronic low-back pain. Both dextrose and saline injections resulted in sustainable and significant improvements in pain disability in chronic low-back-pain patients.⁹
Groin pain. Dextrose prolotherapy resulted in higher full-sport return in athletes who had failed conservative treatment compared for groin pain with every other therapy studied. The sports return rate was as much as surgical options.¹⁰
Knee osteoarthritis. Dextrose injection resulted in substantial long-term functional improvement (twice the minimal clinically important difference).¹¹
ACL laxity. Dextrose intra-articular injections improved pain, swelling and laxity by objective machine measurements progressively to 36 months with KT-100 documented laxity.¹²
Achilles tendonosis. Dextrose prolotherapy resulted in pain reduction accompanied by objective changes in unblinded ultrasound measurements.¹³
Coccygeal pain. Dextrose injection into the coccyx proved effective for persistent pain after coccygeal fracture.¹⁴
Plantar fasciitis. Sonographically guided dextrose injections in patients with chronic plantar fasciitis reduced pain during rest and activity.¹⁵

Conclusion
Prolotherapy is generally not a covered benefit from most insurance companies nor is it covered by Medicare. Nonetheless, it is a valuable tool for relieving and often eliminating difficult pain problems. In my practice, I have seen prolotherapy bring major changes into the lives of my patients. This is especially satisfying when their lives are so limited by pain, like the patient at the beginning of this article. Without the ability to move their body, pain patients are at high risk for serious life-shortening illnesses, including diabetes, hypertension and cardiovascular disease. Prolotherapy may change their lives.

If you have any questions about prolotherapy, feel free to contact me at the email address listed below.

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Dr. Tucker, a sports medicine specialist, is an instructor in proliferative therapy with the Hackett Hemwall Foundation. She practices in Novato and Santa Rosa

Email: gtucker2@gloriatuckermd.com

References
1.  Hackett GS, Henderson DG, “Joint stabilization: an experimental, histologic study with comments on the clinical application in ligament proliferation,” Am J Surg, 80:968-973 (1955).
2.  Liu YK, et al, “In situ study of the influence of sclerosing solution in rabbit medial collateral ligaments and its junction strength,” Connective Tissue Research, 11:95-102 (1983).
3.  Freeman JW, et al, “Effect of prolotherapy on cellular proliferation and collagen deposition in MC3T3-E1 and patellar tendon fibroblast populations,” Transl Res, 158:132-139 (2011).
4.  Klein RC, et al, “Proliferant injections for low back pain,” J Neuro & Ortho Med & Surg, 10:123-126 (1989).
5.  Halpern B, et al, “Clinical and MRI outcomes after platelet-rich plasma treatment for knee osteoarthritis,” Clin J Sports Med, 23:238-239 (2012).
6.  Chang KV, et al, “Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology,” Arch Phys Med Rehab, 95:562-575 (2014).
7.  Hackett GS, et al, Ligament and Tendon Relaxation Treated by Prolotherapy, Charles Thomas (1956).
8.  Cusi M, “Use of prolotherapy in the sacroiliac joint,” Br J Sports Med, 44:100-104 (2010).
9.  Yelland MJ, et al, “Prolotherapy injections, saline injections, and exercises for chronic low-back pain,” Spine, 29:9-16 (2004).
10.  Topol GA, Reeves KD, “Regenerative injection of elite athletes with career-altering chronic groin pain who fail conservative treatment,” Am J Phys Med Rehab, 87:890-902 (2008).
11.  Rabago D, Patterson J, “Hypertonic dextrose injections for knee osteoarthritis,” Ann Fam Med, 11:229-237 (2013).
12.  Reeves KD, Hassanein K, “Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity,” Alt Ther Hlth Med, 9:58-62 (2003).
13.  Ryan M, et al, “Favorable outcomes after sonographically guided intratendinous injection of hyperosmolar dextrose for chronic insertional and midportion Achilles tendonosis,” Am J Roentgen, 194:1047-53 (2010).
14.  Khan SA, et al, “Dextrose prolotherapy for recalcitrant coccygodynia,” J Orth Surg, 16:27-29 (2008).
15.  Ryan MB, et al, “Sonographically guided intratendinous injections of hyperosmolar dextrose/lidocaine,” Br J Sports Med, 43:303-306 (2009).