Prolotherapy

Sclerotherapy roots and George Hackett

A 2010 review in Primary Care by Rabago and colleagues traces the injection of irritant solutions for musculoskeletal pain back roughly a century, and says the modern approach was formalized in the 1950s by George Hackett, a United States general surgeon, drawing on more than 30 years of clinical experience. Hackett published on the idea that loose or relaxed ligaments contribute to joint pain, including a 1959 paper titled 'Ligament relaxation and osteo-arthritis; loose jointed v. close jointed' in the journal Rheumatism.

According to the same review, the older name 'sclerotherapy' reflected an assumption that the injections worked by forming scar tissue. The newer name 'prolotherapy' was chosen to stress a presumed proliferative effect on connective tissue. These names record what early practitioners believed was happening; they do not establish the mechanism.

Changes in solutions and techniques

Rabago and colleagues describe a solution of phenol, glycerine and glucose (often shortened to P2G) in use since the 1960s, sodium morrhuate introduced clinically in the early 1990s, and dextrose at concentrations from 10% to 25%, often mixed with a local anesthetic such as lidocaine. The review also notes that zinc sulfate and very concentrated early solutions, which were associated with serious harms in the 1950s, are no longer in general use.

Since the 2000s, published trials have concentrated on hypertonic dextrose. A 2024 systematic review of randomized trials in sports-related tendinopathy reported that 19 of the 20 included trials used dextrose solutions and only one used a phenol, glycerin and dextrose mixture. Recent studies also describe injections guided by ultrasound rather than by palpation alone.

Names in clinical use

Clinical reviews use 'prolotherapy', 'proliferative therapy' and 'regenerative injection therapy' for the same general approach, and studies often name the treatment after its solution, for example 'dextrose prolotherapy' or 'hypertonic dextrose prolotherapy'. Rabago and colleagues define prolotherapy as an injection-based complementary and alternative therapy for chronic musculoskeletal pain in which a fairly small volume of an irritant or sclerosing solution is injected at painful ligament and tendon insertions and nearby joint spaces over several sessions.

The Cochrane review on low back pain describes prolotherapy as repeated injections of irritant solutions intended to strengthen the ligaments of the lower back, and notes that spinal manipulation and exercise are often used alongside it. Because co-treatments are common, the word 'prolotherapy' in a study may refer to a package of care rather than to injections alone.

Perineural injection therapy and related terms

Perineural injection therapy (PIT) uses a low concentration of dextrose, usually 5%, injected near superficial or peripheral nerves rather than into ligament attachments. A 2026 randomized trial describes 5% dextrose PIT as a low-cost pain treatment, and a 2025 case report uses the name 'Lyftogt perineural injection therapy' after the clinician associated with it. The authors of that case report describe its proposed mechanism in terms of nerve glucose deficit and neurogenic inflammation, which is a hypothesis rather than an established finding.

Prolotherapy is distinct from platelet-rich plasma (PRP), which injects a concentrate prepared from the person's own blood. Reviews sometimes group prolotherapy, PRP and cell-based injections together as 'orthobiologic' or 'regenerative' injections and compare them in the same analysis, but the solutions, preparation and proposed actions differ.

Solutions and proposed mechanisms

Rabago and colleagues state that the precise mechanism is unclear. Proposed explanations include a local inflammatory response triggered by hypertonic dextrose through osmotic effects on cells, direct irritation by phenol-glycerine-glucose, recruitment of inflammatory mediators by sodium morrhuate, and possible stimulation of growth factors involved in soft-tissue repair. These are working theories from the clinical literature, not demonstrated causal pathways in people treated for pain.

A meta-analysis of knee osteoarthritis trials by Wang and colleagues defines hypertonic dextrose prolotherapy as injection of a concentrated dextrose solution for local treatment of musculoskeletal pain and possible enhancement of repair. In the trials summarized by Rabago and colleagues and by later reviews, dextrose is commonly combined with lidocaine to reduce injection pain.

Sessions, sites and who delivers it

The 2010 review describes treatment as several injection sessions given every two to six weeks over several months, often two to five monthly sessions, with injections at ligament and tendon insertions and in adjacent joint spaces. In a blinded Hong Kong trial for knee osteoarthritis, participants received intra-articular injections at weeks 0, 4, 8 and 16. A practitioner survey by Dagenais and colleagues found that 98% of 171 responding prolotherapy practitioners in the United States and Canada held medical degrees.

Rabago and colleagues list training through university continuing medical education courses and through professional groups such as the Hackett-Hemwall Foundation and the American Association of Orthopaedic Medicine. They also state that prolotherapy has no certification by any governing body, similar to corticosteroid injections, and that most patients pay out of pocket. No statutory training standard for the procedure was identified in the sources reviewed.

Conditions practitioners treat

Practitioners use prolotherapy mainly for chronic musculoskeletal pain that has not responded to other treatment. The 2010 review names low back pain, several tendinopathies and osteoarthritis as the conditions with a clinical trial literature, and says that use for many other conditions rests on anecdotal clinical experience. Later trials and reviews cover knee osteoarthritis, lateral elbow pain (tennis elbow), rotator cuff disorders, plantar fasciitis and spinal pain.

Hackett's original rationale was that lax or injured ligaments cause joint instability and pain, and that injections could tighten or strengthen them. That rationale still appears in descriptions of the practice, but the reviews cited here assess pain and function outcomes rather than confirming that ligaments are strengthened in treated people.

Uses for the perineural variant

Perineural dextrose injections have been studied for nerve-related and soft-tissue pain, including shoulder pain linked to rotator cuff tendinopathy, and have been described in case reports for conditions such as persistent facial nerve palsy. A single case report cannot show that a treatment caused an improvement, and the trial and case evidence for this variant is small.

Chronic low back pain

A Cochrane review by Dagenais and colleagues, last updated in 2007, included five trials with 366 participants. Three trials (206 participants) found prolotherapy injections alone no more effective than control injections for pain or disability at six months. Two trials (160 participants) that combined prolotherapy with spinal manipulation, exercise and other therapies reported benefit over control injections, but the co-treatments confound interpretation and the trials could not be pooled. The authors concluded that injections used alone were not effective for chronic low back pain.

A 2026 systematic review of dextrose prolotherapy for chronic spinal pain included 12 studies, mostly case series and cohort studies with only three randomized trials, covering sacroiliac, discogenic and other spinal pain. Most reported pain reduction and no major complications, but the designs cannot separate treatment effects from natural recovery or expectation.

Knee osteoarthritis

Knee osteoarthritis has the largest body of trials. A 2016 meta-analysis by Sit and colleagues included four trials with 258 patients and found dextrose prolotherapy better than exercise alone on WOMAC scores, with moderate heterogeneity. A 2022 meta-analysis by Chen and colleagues pooled 14 randomized trials with 978 patients and found favorable effects on pain and function compared with placebo injections and non-invasive control therapy, and broadly similar effects to other injection therapies, but warned that marked heterogeneity and risk of bias call for caution.

In a single-center blinded trial of 76 patients in Hong Kong, intra-articular dextrose produced a 10.34-point greater improvement on the 100-point WOMAC pain score than saline at 52 weeks, with no adverse events reported. A 2021 meta-analysis of six studies (395 participants) found no significant short-term difference in pain between dextrose prolotherapy and hyaluronic acid injections overall, with a difference favoring prolotherapy only in a subgroup that used intra-articular injection.

Tendinopathy and the perineural variant

For lateral elbow tendinosis, a 2022 meta-analysis of eight trials (354 patients) found dextrose prolotherapy better than active controls at 12 weeks for pain (standardized mean difference -0.44) and arm function, while noting the studies were too small to detect rare adverse events.

Results for rotator cuff disorders are weaker. A 2025 meta-analysis of eight studies (431 participants) found no significant difference from control or placebo treatments in pain or disability scores. A 2026 review from a United States Veterans Affairs evidence center, covering 14 studies, rated the evidence versus saline as very uncertain and concluded dextrose may have little to no benefit, and probably worse physical performance than corticosteroid injection. A 2026 sham-controlled trial of 39 people found short-term pain reduction with distal perineural 5% dextrose, but not with a proximal injection site.

Common side effects

Rabago and colleagues report that pain, a feeling of fullness and numbness at injection sites are common, and that 10% to 20% of trial participants have a post-injection pain flare within 72 hours, usually settling within five to seven days. In the practitioner survey by Dagenais and colleagues, the side effects with the highest estimated prevalence after back and neck prolotherapy were pain (median estimate 70%), stiffness (25%) and bruising (5%).

Knee and elbow trials reviewed here mostly reported no major adverse events, but reviewers note that small trials cannot detect rare harms, and the 2026 rotator cuff review found adverse-event reporting sparse and of very low certainty.

Serious events with spinal injections

The 2006 survey of 171 practitioners, who reported a median of 2,000 treatments each, collected 472 adverse events from back and neck prolotherapy, including 69 that required hospitalization and 5 permanent injuries from nerve damage. Most were linked to needle placement: spinal headache (164 reports), pneumothorax or collapsed lung (123), temporary systemic reactions (73), nerve damage (54), hemorrhage (27), spinal cord insult such as meningitis, paralysis or spinal cord injury (9) and disk injury (2). Because these are practitioner recollections, the true frequency cannot be calculated from them.

Rabago and colleagues also summarize older reports of neurological harm from spinal injections, including a 1959 death after zinc sulfate injections for low back pain and a 1960 report of paraplegia after sclerosing agents. They note that zinc sulfate and the very concentrated solutions involved are no longer in general use.

Contraindications and care boundaries

The 2010 review lists acute local infection, such as cellulitis, abscess or septic arthritis, as an absolute contraindication, and acute gout or an acute fracture as relative contraindications. The sources reviewed did not report infection rates after prolotherapy, and they do not establish suitability for any individual. Chronic joint or back pain can have causes that need medical assessment, and prolotherapy should not delay or replace necessary diagnosis or care.