Prolotherapy Injection

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Prolotherapy, also known as proliferative therapy or regenerative injection therapy, is a treatment modality with a long history of use for chronic musculoskeletal pain. Formalized by Dr. George Hackett in the 1950s and further developed and taught by Dr. Gustav Hemwall, prolotherapy initially focused on treating pain attributed to ligament and tendon laxity, particularly in the spine and pelvis. The core principle involves injecting small amounts of a mild irritant or "proliferant" solution at painful sites, such as ligament and tendon insertions (entheses) or within joint spaces, to stimulate the body's innate healing mechanisms.

Proposed Mechanism of Action:

While various solutions have been used, hypertonic dextrose is currently the most common and well-studied proliferant, largely due to its efficacy and favorable safety profile. The proposed mechanism by which dextrose prolotherapy promotes tissue repair involves several steps:

1. Initial Irritation and Inflammation: The injection of a hypertonic dextrose solution (typically 12.5% to 25%) into the target tissue creates a localized osmotic shock. This hyperosmolarity causes fluid to shift out of local cells, leading to cell dehydration and lysis (rupture). This controlled micro-injury mimics a new trauma, initiating an acute, localized inflammatory cascade.
2. Growth Factor Cascade: The inflammatory response involves the influx of neutrophils, macrophages, and other immune cells to the injection site. These cells, along with the lysed local cells, release a variety of potent signaling molecules, including growth factors (e.g., platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF)) and cytokines. In vitro studies confirm that dextrose can stimulate the production of these growth factors by human fibroblasts and chondrocytes.
3. Tissue Proliferation and Remodeling: The released growth factors orchestrate the proliferative phase of healing. They stimulate the migration and proliferation of local fibroblasts, the primary cells responsible for producing connective tissue matrix. These activated fibroblasts synthesize and deposit new extracellular matrix components, primarily collagen (initially disorganized Type III collagen, which is subsequently remodeled into stronger, more organized Type I collagen), as well as elastin and proteoglycans. This process leads to the thickening, strengthening, and stabilization of the treated ligaments, tendons, or fascial structures. Animal studies have shown increased ligament mass, thickness, and junction strength following dextrose prolotherapy.

This cascade effectively restarts the natural healing process in tissues that may be caught in a state of chronic degeneration or incomplete repair, often characterized histologically by collagen disorganization and a lack of inflammatory cells (tendinosis rather than tendinitis).

Evidence for Effectiveness

Numerous clinical studies, including randomized controlled trials (RCTs) and systematic reviews, have investigated the efficacy of dextrose prolotherapy for various musculoskeletal conditions. Systematic reviews suggest that prolotherapy is an effective treatment for several tendinopathies (including lateral epicondylitis, Achilles tendinopathy, Osgood-Schlatter disease, rotator cuff tendinopathy, plantar fasciitis), osteoarthritis (particularly of the knee and finger joints), and spinal/pelvic pain related to ligament dysfunction (e.g., sacroiliac joint pain). Studies often report significant improvements in pain and function compared to baseline, saline injections, or exercise therapy.

However, the overall body of evidence is not without limitations. Some systematic reviews and individual trials have yielded conflicting results, particularly for chronic low back pain. Methodological concerns in some studies include small sample sizes, heterogeneity in patient populations, variability in injection protocols (dextrose concentration, number and location of injections, frequency of sessions), use of co-interventions, reliance on subjective outcome measures, and short follow-up durations. These inconsistencies contribute to the position taken by some healthcare organizations and payers that prolotherapy remains investigational for certain indications. It is plausible that the historical variability in outcomes could be partly attributed to imprecise diagnostic targeting based primarily on palpation. A more targeted approach, guided by advanced diagnostics like dynamic ultrasound informed by biotensegrity principles to identify specific sites of fascial dysfunction, may lead to more consistent and robust clinical results, potentially strengthening the evidence base for the therapy in the future.

Safety and Solutions

Dextrose is favored due to its established safety record; it is water-soluble, a normal body constituent, and generally well-tolerated even with multiple injections. Local anesthetics like lidocaine or procaine are often added to the solution to minimize injection discomfort. While generally safe, potential contraindications exist, including acute infections, bleeding disorders, allergies to components, and potentially pre-existing severe systemic conditions. Other less common proliferants include phenol-glycerine-glucose (P2G) and sodium morrhuate.

Other Agents

Some use tetradecyl (2mL 3% tetradecyl diluted in 50mL vial of prilocaine to make 0.11%) or polidocanol for those with sulfate allergies.

Dextrose can be obtained by MPSO, while tetradecyl and polidocanol can be obtained from NZ scientific and medical.

Articles

Prolotherapy for the thoracolumbar fascia - Fullerton 2018 - 2.49 MB (f)

Also see Hauser et al for a free open access systematic review from 2016.

Literature Review

Literature Review

Reviews from the last 7 years: review articles, free review articles, systematic reviews, meta-analyses, NCBI Bookshelf

Articles from all years: PubMed search, Google Scholar search.

TRIP Database: clinical publications about evidence-based medicine.

Other Wikis: Radiopaedia, Wikipedia Search, Wikipedia I Feel Lucky, Orthobullets,