Prolotherapy Summary

While the body of evidence may not yet be sufficient, the purported significant long-term, sustained benefit, along with the decreased use of pain medications and relative safety of the treatment, make prolotherapy a very appealing option to practitioners. Current data suggest that prolotherapy has a positive effect compared with baseline status, and in some cases compared with control therapy, in carefully selected patients for several indications. However, prolotherapy cannot as yet be considered a first-line option for the treatment of various musculoskeletal conditions because significant information is still lacking. As an example, standardized dosages, formulations, and treatment schedules have not been established, with some authors attributing a few adverse effects to possibly using too high of a dose and total volume of fluid in their study. This lack of consistency can lead to potential confusion when attempting to apply these results clinically.

MECHANISM OF ACTION

Prolotherapy works by causing a temporary, low grade inflammation at the site of ligament or tendon weakness (fibrosseous junction), “tricking” the body into initialing a new healing cascade. Inflammation activates fibroblasts to the area, which synthesize precursors to mature collagen, reinforcing connective tissue. This inflammatory stimulus raises the level of growth factors to resume or initiate a new connective tissue repair sequence to complete one which had prematurely aborted or never started. Prolotherapy is also known as “regenerative injection therapy (RIT),” “non-surgical tendon, ligament, and joint reconstruction” or “growth factor stimulation injection therapy.”

Although multiple mechanisms have been proposed for the targeted cellular pathways resulting in an inflammatory state including cellular osmotic rupture, chemotactic attraction of inflammatory mediators, or an increase in the antigenicity of host cells, these pathways have not been studied  in vivo . Regardless of pathway, leukocyte and macrophage infiltration does occur initially with injection of the  aforementioned agents.

Ultimately, the inflammatory response may improve pain by reducing inappropriate neovascularization and accompanying neural ingrowth at sites of chronic tendinopathy.  However, tendon and/or ligament structural changes may be what promote symptomatic relief.

INJECTION TECHNIQUE

Many different proliferant or sclerosing agents have been identified and used in studies. Agents typically involve a mixture of hypertonic dextrose (10%–30%), morrhuate sodium, or phenol-glycerine-glucose. Injections are placed into the affected tendon, ligament, or joint and repeat injections are often necessary to stimulate enough of an inflammatory response.

Study protocols vary, although they typically involve repeated injections every 2 to 6 weeks over the course of months. Complications of injection are local and parallel other injection therapies. Patients are generally asked not to take anti-inflammatory medications because this may interrupt the controlled and targeted inflammatory process. Injections can be given to patients as first-line therapy, but most studies have described the usage of prolotherapy for those with conditions refractory to other nonsurgical care.

Conditions that can be treated with Prolotherapy

OSTEOARTHRITIS

Prolotherapy has been used successfully even after the diagnosis of osteoarthritis and degenerative joint disease. This may be because of its ability to strengthen the existing intact, but weakened, ligamentous and tendinous structures.  Clinical evidence exists that prolotherapy can help to stimulate cartilage regenera tion, although no specific controlled studies have yet been done to confirm this. Laboratory studies have demonstrated that cartilage cells respond to injury (inflammation) by changing into chondroblasts, cells capable of cell proliferation, growth, and healing. Therefore, it would be logical that in vivo use might stimulate a similar phenomenon.

The response produced by hyperosmolar dextrose solutions may have some effect on osteoarthritis progression and cartilage regeneration in animal models. These studies had small sample sizes; however, the authors suggest that their results are driven by increases in the tissue osmolarity and glucose availability, which stimulate chondrocyte proliferation and subsequent production of extracellular matrices. One human study looked at the chondrogenic effects of hypertonic dextrose injections placed into severely arthritic knees based on pre- and post injection arthroscopy and biopsies. Although this study was also limited in sample size, the authors saw increases in metabolically active hyaline- and fibrolike cartilage and significant increases in functional scores.

MENISCAL INJURY

Medial meniscus firmly adheres to the deep surface of the medial collateral ligament (MCL), an important stabilizing ligament. Therefore injury to the medial meniscus will very often also result in injury and sprain to the MCL. The cause of the knee pain may be the MCL sprain, but MCL sprains are usually not addressed, especially if the MRI shows a meniscal tear. This could explain pain persisting after meniscal surgery. Clearly, the presence of meniscal tears on MRI needs to be correlated to an individual’s pain complaint. Pain may not be related to the abnormal findings on an MRI, but rather may be due to ligament or tendon injury or sprain/strain. In fact, individuals with abnormal MRI’s showing meniscal tears have successfully been treated with prolotherapy. It is unclear whether prolotherapy has any direct effect on meniscal tissue, and this has not been specifically studied. However, even when patients have these meniscal abnormalties on MRI, they often improve after prolotherapy treatment.

ANTERIOR CRUCIATE LIGAMENT INJURY

The Anterior Cruciate Ligament (ACL) is an important ligament for anterior-posterior stability of the knee. If the ACL is completely ruptured, surgery is needed. However, for partial ACL injury, prolotherapy is a reasonable treatment option and should be considered prior to surgery. If any residual pain exists, the ligament has likely been permanently lengthened, resulting in an unstable knee. As discussed above, leaving an unstable ligament will result in a change in biomechanics and development of osteoarthritis. Prolotherapy can be used in this situation to repair the overstretched ligament and stimulate healing so that stability is restored.

PATELLOFEMORAL PAIN SYNDROME (PFPS)

Patellofemoral pain is the most common cause of anterior knee pain,48 usually presenting with vague symptoms of pain “in,” “under,” or “behind” the patella or in the peri-patellar area. Symptoms are exacerbated by activities such as running, descending stairs, and squatting, as well as prolonged sitting with the knee in a flexed position (“theatre sign”). Twenty- five percent of the population, at some stage in their lives, suffer from this condition. Despite this, there is little agreement on the terminology, etiology, or treatment. The term “chrondromalacia patellae” is sometimes used, but is now reserved for a small subset of anterior knee pain with documented softening of the patellar articular cartilage. There is little evidence to support the use of knee braces or NSAIDs in PFPS. This condition has been successfully treated with prolotherapy.

LATERAL EPICONDYLITIS

Although the term lateral epicondylitis (LE) implies an inflammatory process, LE is degenerative in nature, spurred by repetitive microtrauma leading to an attempt by the body to heal by upregulating local angiogenesis and fibroblast proliferation. Scarpone et al conducted a double-blind RCT as a pilot to investigate the efficacy of combined dextrose/sodium morrhuate prolotherapy for LE. Twenty-four participants with at least 6 months of refractory LE were randomized to receive injections of either the sclerosing solution or normal saline at 0, 4, and 8 weeks. The experimental group demonstrated significantly better levels of elbow pain at all time points through 1 year and isometric strength testing at final in-person follow up at 16 weeks. Improvements in grip strength were seen in both groups and were not significantly different between groups. There were no complications of treatment other than self-limited postinjection site pain.

LOW BACK PAIN

There  is  conflicting  evidence  regardingthe  efficacy  of  prolotherapy  injections  in  reducing  painand disability in patients with chronic low back pain. Con-clusions are confounded by clinical heterogeneity amongstudies  and  by  the  presence  of  co-interventions.  Therewas no evidence that prolotherapy injections alone weremore effective than control injections alone. However, inthe presence of co-interventions, prolotherapy injectionswere more effective than control injections, more so when both injections and co-interventions were controlled concurrently.

SIDE EFFECTS

The risks associated with prolotherapy are minor, especially compared to the potential risks of surgery and other procedures. These are a few of the potential side effects a patient can experience after prolotherapy:

  • Swelling and inflammation around the injection site
  • Pain and stiffness
  • Headaches
  • Allergic reaction to the injected solution
  • Nerve related issues

With most prolotherapy procedures you can expect to feel a small amount of stiffness, discomfort, or pain in the area for the hours or days following the procedure. This is completely normal. However, if the pain or other symptoms persist or get worse over time, please contact your doctor urgently.

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