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Prolotherapy

Overview

Prolotherapy (proliferative therapy) is an injectable, non-surgical orthopedic treatment that uses small volumes of hypertonic dextrose (a medical-grade sugar solution) mixed with saline to stimulate a localized tissue response. It has been used for decades in the management of chronic musculoskeletal pain, particularly conditions involving ligamentous laxity, joint instability, and enthesopathic pain.

Prolotherapy is best understood as a mechanical–biologic intervention. The injected solution creates a controlled local stimulus that may initiate a cascade of inflammatory and reparative signaling, potentially supporting tissue strengthening and improved joint stability over time. (1-3)

Mechanism of Action (Current Understanding)

Hypertonic dextrose is believed to act through several complementary mechanisms:

Local inflammatory stimulation: Dextrose concentrations above physiologic levels create an osmotic and chemical stimulus that induces a mild, controlled inflammatory response at ligament and tendon insertions (entheses). This response is theorized to promote fibroblast activation and connective tissue remodeling. (1,2)

Neuromodulatory effects: Emerging evidence suggests that dextrose may directly modulate nociceptive signaling, potentially reducing pain by altering peripheral nerve activity, particularly in chronic pain states. (4,5)

Mechanical stabilization over time: In conditions characterized by joint hypermobility or ligamentous insufficiency, repeated prolotherapy injections may improve subjective stability and function as connective tissue adapts. (1-3)

Importantly, prolotherapy does not involve tissue replacement, stem cell transplantation, or engineered regeneration. Its clinical effects, when present, are gradual and depend on tissue response, diagnosis accuracy, and appropriate patient selection.

Clinical Applications

Prolotherapy has been studied across a range of musculoskeletal conditions, with the strongest and most consistent evidence supporting its use in chronic ligament- and joint-based pain syndromes, including:

Sacroiliac (SI) Joint Dysfunction and Hypermobility

  • SI joint pain related to ligamentous laxity or instability is one of the most commonly cited and studied indications for prolotherapy.

  • Randomized and prospective studies report improvements in pain and function in selected patients with chronic SI joint pain when compared with conservative care or other injection approaches. (2,3)

Other Musculoskeletal Conditions (Selected Cases)

  • Chronic low back pain with ligamentous involvement

  • Tendinopathies and enthesopathies

  • Peripheral joint instability (e.g., knee, shoulder, ankle)

Clinical outcomes vary, and prolotherapy is typically considered after failure of conservative measures such as physical therapy, activity modification, and medications.

The Prolotherapy Procedure

Visit duration

Patients should expect a total visit time of approximately 30–60 minutes, with the injection procedure itself typically lasting 10–20 minutes.

Step-by-step process

1. Clinical evaluation and planning: Diagnosis is confirmed through history, physical examination, and imaging, as appropriate. Prolotherapy is offered only when there is a plausible anatomic and biomechanical rationale.

2. Local anesthesia (optional): A local anesthetic may be used to improve comfort before injection. Anesthetic selection and dosing are chosen to minimize tissue toxicity while providing adequate analgesia.

3. Injection technique: A solution of hypertonic dextrose and saline is injected into targeted ligamentous or periarticular structures.

  • Ultrasound guidance is commonly used to improve accuracy and avoid surrounding structures.

  • Fluoroscopy may be used for deeper or more complex anatomy, particularly in the sacroiliac joint.

4. Post-procedure expectations: Mild to moderate soreness is common for several days following treatment and reflects the intended local tissue response. Improvement, when it occurs, is typically gradual and may require a series of injections spaced over weeks to months. (1-3)

Safety and Tolerability

Prolotherapy is generally well tolerated when performed using sterile technique and appropriate imaging guidance. Reported adverse effects are usually mild and self-limited, including post-injection soreness or stiffness. Serious complications are uncommon. (1-3)

Prolotherapy may not be appropriate for patients with:

  • Active infection

  • Uncontrolled bleeding disorders

  • Certain systemic inflammatory or metabolic conditions (case-specific)

These considerations are reviewed during consultation.

Regulatory Considerations

Prolotherapy uses dextrose and saline, both of which are FDA-approved substances. However, prolotherapy itself is not FDA-approved as a specific treatment for musculoskeletal conditions. Its clinical use is based on physician judgment, available scientific evidence, and individualized patient evaluation.

No claims are made regarding guaranteed outcomes, permanent structural repair, or disease modification.

Is Prolotherapy Right for You?

Prolotherapy may be considered for patients with chronic musculoskeletal pain, particularly SI joint dysfunction or hypermobility, who have not achieved adequate relief with conservative therapies and who understand that results vary.

If you believe you may be a candidate, we encourage you to contact our clinic for a comprehensive evaluation.

References

1.     Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Primary Care. 2010;37(1):65–80. doi:10.1016/j.pop.2009.09.013.

2.     Kim WM, Lee HG, Jeong CW, et al. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. Pain Physician. 2010;13(4):363–370. PMID: 20648206.

3.     Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2016;9:139–159. doi:10.4137/CMAMD.S39160.

4.     Duman I, Taskaynatan MA, Tan AK, et al. Relief of chronic pain by perineural injection of dextrose: potential neurogenic mechanism. Medical Hypotheses. 2012;78(1):21–24. doi:10.1016/j.mehy.2011.09.033.

5.     Wu YT, Ke MJ, Ho TY, et al. Dextrose injection for chronic musculoskeletal pain: a narrative review. Pain Research & Management. 2017;2017:8157910. doi:10.1155/2017/8157910.

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