Prolotherapy, short for “proliferative therapy,” is a medical procedure that involves the injection of a natural irritant solution into injured or weakened connective tissues, typically in and around joints, to stimulate the body’s natural healing response. This therapy is used primarily for the treatment of chronic musculoskeletal pain, particularly in cases of ligament and tendon injuries, and is considered a form of regenerative medicine. Irritant solutions used for prolotherapy often contain highly concentrated dextrose. More recently, autologous cellular solutions, such as platelet-rich plasma (PRP), bone marrow, or adipose tissue, are also being used. In this article, we will delve into the basics of prolotherapy, its mechanism of action, clinical applications, success rates, and future directions.

Mechanism of Prolotherapy

The fundamental principle behind prolotherapy is to induce a controlled inflammatory response at the site of injury. This is achieved through the injection of a solution typically composed of dextrose (a type of sugar), saline, or other irritants. The injected solution irritates the weakened or injured connective tissue, such as ligaments or tendons, prompting the body’s natural healing mechanisms to repair the damaged area.

Key steps in the mechanism of prolotherapy include:

1. Inflammation: The injected irritant solution triggers a mild inflammatory response, leading to an influx of immune cells and growth factors to the site of injury.

2. Tissue Repair: This influx of growth factors and immune cells facilitates the repair and regeneration of the injured connective tissue, including the strengthening of ligaments and tendons.

3. Pain Reduction: As the tissue becomes stronger and more stable, chronic pain is alleviated, and joint stability is improved.

Clinical Applications

Prolotherapy has been used to treat a variety of chronic musculoskeletal conditions, including:

1. Chronic Joint Pain: Commonly used to address pain in joints, particularly those in the back, knees, shoulders, and hips.

2. Ligament and Tendon Injuries: Effective in treating injuries to ligaments and tendons, such as sprains and strains.

3. Osteoarthritis: Provides relief for pain associated with osteoarthritis by strengthening the joint’s supporting structures.

4. Sports Injuries: Often used by athletes to accelerate the healing process of injuries and return to their activities more quickly.

5. Lower Back Pain: Prolotherapy is a viable option for patients with chronic lower back pain, especially when other treatments have been ineffective.

6. Temporal Mandibular Joint (TMJ) Dysfunction: Prolotherapy can help alleviate pain and discomfort associated with TMJ disorders.

The Prolotherapy Procedure

The prolotherapy procedure typically follows these steps:

1. Patient Evaluation: The physician evaluates the patient’s medical history, conducts a physical examination, and identifies the source of pain or instability.

2. Solution Injection: The irritant solution is injected directly into the targeted ligaments, tendons, or joints. Local anesthesia may be used to minimize discomfort during the procedure.

3. Recovery: After the procedure, patients may experience temporary soreness and swelling at the injection site. Over a series of sessions, the body’s natural healing processes will strengthen the damaged tissues.

4. Follow-up: Patients are typically recommended a series of prolotherapy sessions, with each session spaced several weeks apart, to maximize the therapeutic effect.

Success Rates and Considerations

Success rates of prolotherapy can vary depending on the patient, the condition being treated, and the physician’s experience. Some individuals experience significant pain reduction and improved joint stability after completing a series of prolotherapy sessions. Others may require additional treatments or complementary therapies.

Considerations for prolotherapy:

– Safety: Prolotherapy is generally considered safe, with minimal side effects. However, like any medical procedure, there can be risks, such as infection or nerve injury.

– Cost: The cost of prolotherapy can vary and may not always be covered by insurance.

– Patient Selection: The ideal candidate for prolotherapy is someone with chronic musculoskeletal pain, who has not responded to more conservative treatments.

Future Directions

The field of prolotherapy continues to evolve, with ongoing research to refine techniques, improve patient selection, and enhance the understanding of its mechanisms of action. Future directions in prolotherapy may include:

1. Personalized Treatment: Tailoring prolotherapy based on the patient’s unique needs and characteristics.

2. Combination Therapies: Exploring prolotherapy in combination with other regenerative medicine techniques, such as platelet-rich plasma (PRP) or stem cell therapy.

3. Advanced Imaging: Utilizing advanced imaging techniques to enhance the precision of injection and evaluate treatment outcomes.


Prolotherapy is a regenerative injection therapy that offers a non-surgical and minimally invasive approach to treating chronic musculoskeletal pain. By stimulating the body’s natural healing processes, it can provide relief to individuals suffering from ligament and tendon injuries, osteoarthritis, and chronic joint pain. While research continues to refine its application, prolotherapy stands as a valuable option in the realm of regenerative medicine, offering hope for those seeking a non-pharmaceutical, non-surgical solution to their chronic pain.

Prolotherapy remains unproven at present. Studies show that it offers modest pain relief, but many experts say evidence of its effectiveness and safety is still lacking. A recent systematic review and meta-analysis published in the clinical journal of orthopedic trauma by Wee and his colleagues (2021 May 20;19:108–117) concluded prolotherapy in knee osteoarthritis confers potential benefits for pain, but the studies had a high risk of bias. Based on two well-designed studies, dextrose prolotherapy may be considered for knee osteoarthritis (strength of recommendation B). This treatment is safe and may be considered for patients with limited alternative options (strength of recommendation C).

Similarly, a recent publication in the Journal of Back and Musculoskeletal Rehabilitation by Hauser et al. (2022;35(4):701–712) concluded that non-biologic prolotherapy or cellular prolotherapy, including platelet-rich plasma (PRP), can be beneficial in restoring spinal stability and resolving chronic low back pain.

Credits & Sources:

  1. PubMed
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