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You are here: Home / Arthritis and joint disorders / Prolotherapy – Types, Mechanism and Uses

Prolotherapy – Types, Mechanism and Uses

Dr Arun Pal Singh ·

Last Updated on March 16, 2025

Prolotherapy is an injection-based therapy for chronic musculoskeletal pain where the non-pharmacological and non-active irritant solution is injected into the body to strengthen weakened connective tissue. Earlier, it was called sclerotherapy because the injected solutions were thought to be scar-forming. Now it is presumed to have a proliferative effect on the injured tissue and is therefore called prolotherapy. It has also been called regenerative injection therapy.

It is a complementary and alternative medical (CAM) therapy for chronic musculoskeletal pain and is claimed to restore joint and tissue function by enabling cells to regenerate and restore normal function without stem cells.

Though many studies support the use of prolotherapy, conclusive evidence for its use is still being gathered.

Contents hide
1 How Does Prolotherapy Work?
2 Different Types of Prolotherapy
3 Mechanisms
4 Conditions where Prolotherapy is Used
5 Contraindications of Prolotherapy
6 Procedure
7 Adverse Effects of Prolotherapy
8 Special Note
8.1 References

How Does Prolotherapy Work?

Prolotherapy treatment usually consists of several injection sessions every 2 to 6 weeks over several months. During a session, therapeutic solutions, also called proliferants, are injected at the intended painful sites like ligaments, tendons, or joint spaces. Most injections can be done in an office setting, where required ultrasound guidance may be taken

These proliferants are thought to cause local irritation and inflammation which is followed by tissue healing.  This results in the enlargement and strengthening of damaged ligaments, tendons, and intra-articular structures. These are thought to improve joint stability, biomechanics, and function leading to a decrease in pain.

prolotherapy injection

 

Different Types of Prolotherapy

  • Growth factor injection: In this procedure, a growth factor is injected which affects the growth of a certain cell line (For example injection of erythropoietin to increase red blood cells)
  • Growth factor stimulation: In this procedure, a substance that causes the body to produce growth factors is injected. Human cells exposed to as little as 0.3% dextrose produce growth factors such as platelet-derived growth factor, transforming growth factor-beta, epidermal growth factor, basic fibroblast growth factor, and connective tissue growth factor.
  • Inflammatory: This involves the injection of a substance that causes activation of the inflammatory cascade to produce growth factors. Examples of solutions in current use are 12.5%-25% dextrose, phenol-containing solutions, and sodium-morrhuate-containing solutions. Sodium morrhuate is the sodium salt of the fatty acids in cod liver oil.

Mechanisms

Many proliferants have been used historically, including glycerine, phenol, platelet-rich plasma, and sodium morrhuate. Today, hypertonic dextrose,  also known as hyperosmolar dextrose is the most commonly used proliferant.

Hyperosmolar dextrose (10-30%) is a water-soluble solution that has a good safety profile and is cost-effective, and water-soluble.  Hyperosmolar dextrose causes osmotic shock and dehydration that leads to a release of cytokines and growth factors and eventually tissue proliferation. This results in new tissue deposition at the damaged site. Hyperosmolar dextrose has been used in lower back pain, sacroiliac joint pain, and osteoarthritis.

Phenol-glycerine-glucose (P2G) and morrhuate sodium are used less commonly. P2G acts by local cellular irritation and morrhuate sodium acts by chemotactic attraction of inflammatory mediators.

Conditions where Prolotherapy is Used

  • Low Back Pain (LBP)
  • Lateral epicondlylitis
  • Plantar fasciitis.
  • Achilles tendinopathy
  • Hip adductor tendinopathy
  • Knee osteoarthritis
  • Carpal tunnel syndrome

Contraindications of Prolotherapy

Contraindications for patients to receive prolotherapy injections may include

  •  Local abscess
  • Bleeding disorders
  • The patient on anticoagulant medication
  • Known allergy to prolotherapy agent
  • Acute infections such as cellulitis
  • Septic arthritis

Procedure

Patients who are going to receive prolotherapy mustn’t take anti-inflammatory medications for 2 to 3 days before the procedure. It is desirable as antiinflammatory drugs would prevent inflammation required for cell regeneration.

On the day of the prolotherapy, a person must eat well.

For the procedure, after positioning the part is cleaned with sterilizing solution. A local anesthetic may be applied for a numbing effect. In anxious patients, additional sedation may be required and that procedure may be shifted from the outpatient department to a place where the patient can be better monitored.

After the preparation, a long thin needle is used to to deliver the irritant solution to several different points around the target area in the back or joint. The number of injections used depends on the area or joint affected.

After the needle is withdrawn, mild compression is given for some time, and the patient is kept under observation. The patient is encouraged to mobilize the part within the limits of pain.

Adverse Effects of Prolotherapy

  • Pain
  • Mild bleeding
  • Occasional numbness
  • Pain flares
    • Typically self-limited
    • Respond well to paracetamol tablets
  • Allergic reaction (rare)
  • Infection (rare)

Special Note

Recently a systematic review has hinted that prolotherapy is effective in tennis elbow and osteoarthritis. However, we require more studies before conclusive evidence is obtained for its use in routine practice.

References

  • Hauser RA, Lackner JB, Steilen-Matias D, et al. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clin Med Insights Arthritis Musculoskelet Disord 2016;9:CMAMD.S39160. https://doi.org/10.4137/CMAMD.S39160
  • Eslamian F, Amouzandeh B. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up. Ther Adv Musculoskelet Dis. 2015 Apr;7(2):35-44. [Pubmed]
  • Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016 Jul 7;9:139-59

Arthritis and joint disorders This article has been medically reviewed by Dr. Arun Pal Singh, MBBS, MS (Orthopedics)

About Dr Arun Pal Singh

Dr. Arun Pal Singh is a practicing orthopedic surgeon with over 20 years of clinical experience in orthopedic surgery, specializing in trauma care, fracture management, and spine disorders.

BoneAndSpine.com is dedicated to providing structured, detailed, and clinically grounded orthopedic knowledge for medical students, healthcare professionals, patients and serious learners.
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Dr. Arun Pal Singh is an orthopedic surgeon with over 20 years of experience in trauma and spine care. He founded Bone & Spine to simplify medical knowledge for patients and professionals alike. Read More…

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