Prolotherapy: Can a Little Inflammation Help Joints Heal?

Have you ever heard of “Prolotherapy“? I didn’t think so. It’s not an approach most physical therapists or orthopedic specialists learn about during their residencies. Prolotherapy is based on an idea that sounds almost upside down: instead of suppressing inflammation in a painful joint, ligament or tendon, a clinician deliberately provokes a small, controlled response in hopes of stimulating repair. Now that the familiar RICE prescription for sprains and strains is being reconsidered, this old treatment deserves another look.

For nearly half a century, injured athletes and weekend warriors were told to rely on RICE: Rest, Ice, Compression and Elevation. The goal was to limit swelling and calm inflammation as quickly as possible.

But researchers are now asking whether inflammation is always the enemy. Could suppressing the body’s initial response to an injury sometimes interfere with healing? You can read my recent deep dive into reconsideration of RICE at this link.

A Sprained Ankle Without RICE

One reader discovered a very different way to treat an injured ankle:

Q. One summer I managed to sprain the same ankle twice. The first time I followed RICE and wore a wrap on the joint for several days before it felt better.

After I sprained my ankle the second time, I immediately immersed it in water as warm as I could tolerate for about 15 minutes. I then elevated the joint and began moving it gently. I also had my husband apply light traction to the joint. The next day it was as though the sprain had never occurred.

A. RICE—rest, ice, compression and elevation—used to be recommended routinely for most injuries. It has now lost favor, as described in this recent website article. Your second approach appears to have worked better for you.

That does not prove that hot water or traction will cure a sprained ankle. A severe sprain may involve torn ligaments, and an apparent sprain can sometimes be a fracture. Anyone who cannot bear weight, has marked swelling or deformity, or experiences worsening pain should seek medical attention promptly!

The reader’s experience does, however, fit with a changing understanding of tissue repair. Complete rest and prolonged icing may not always be the best route to recovery. Carefully chosen movement can help maintain circulation, preserve mobility and signal injured tissue that it needs to rebuild.

What Does Prolotherapy Have to Do With RICE?

A reader identified as CW responded to our recent article on rethinking RICE:

“The position that the RICE method is a flawed healing strategy has been professed for years by doctors who practice prolotherapy. Prolotherapy is represented by a range of injection methods used to stimulate the growth of new tissue and heal connective tissue. Rather than suppressing the inflammatory process required for healing, prolotherapy stimulates inflammation in a controlled manner. And instead of rest, prolotherapists often encourage gentle movement.”

That is a good description of the central theory. Conventional treatment often tries to extinguish inflammation. That’s the whole idea behind NSAIDs (nonsteroidal anti-inflammatory drugs) such as celecoxib, ibuprofen, naproxen and meloxicam).

Prolotherapy attempts to use a localized stimulus to recruit the body’s repair machinery. The term generally refers to injections of an irritating solution into or around painful joints, ligaments or tendon attachments. Hypertonic dextrose—concentrated sugar water—is the solution most commonly studied.

Proponents believe that the injection may stimulate local signaling, growth factors and tissue-repair processes. The exact mechanism remains unsettled, however, and prolotherapy should not be portrayed as proven cartilage regeneration.

A narrative review (Physical Medicine and Rehabilitation Clinics of North America, Feb. 2023) described prolotherapy as:

“a nonsurgical regenerative technique that allows small amounts of irritant solution to be injected into the site of painful tendon and ligament insertions to promote the growth of healthy cells and tissues. The goal of prolotherapy is to stimulate growth factors that may strengthen attachments and reduce pain.”

The authors go on to suggest that this approach may be beneficial for a number of muscular-skeletal conditions:

• Low back pain
• Sacroiliac joint pain
• Osteoarthritis
• Plantar fasciitis
• Achilles tendinopathy
• Rotator cuff tendinopathy
• Tennis elbow

Is Prolotherapy the Same as PRP?

Not quite. Traditional dextrose prolotherapy uses a concentrated sugar solution. Platelet-rich plasma, or PRP, is prepared from the patient’s own blood. The platelets are concentrated and injected into the painful area because they contain signaling molecules involved in wound healing.

Other regenerative approaches include medicinal signaling cells, sometimes called mesenchymal stem cells, and autologous conditioned serum. These procedures differ greatly in preparation, cost, regulation and scientific support. They should not all be placed into one regenerative-medicine bucket.

Prolotherapy is usually simpler and less expensive than PRP or cell-based procedures, although insurance often does not cover it.

A recent radio show describes many of these regenerative techniques. If you would like to learn more about them, you might want to take a few minutes to listen to a highly qualified expert describe the process:

Show 1468: Healing Joints and Nerves: The New Science of Regenerative Therapies
Exercise is crucial, but what if it hurts to move? Learn about regenerative therapies such as PRP, MSC and autologous conditioned serum.

What Does the Research Show About Prolotherapy?

When we first wrote about prolotherapy more than a decade ago, we cited a review of ten studies that found “moderate evidence” that the treatment could provide symptom control for osteoarthritis.

The literature has grown since then, but the answer is still not a simple yes or no.

A 2024 systematic review and meta-analysis in Health Science Reports, June 24, 2024 concluded that dextrose prolotherapy:

“exhibits promising effectiveness in reducing joint pain and stiffness, as well as improving functional performance in individuals suffering from KOA [knee osteoarthritis].”

The authors also emphasized that results can be affected by age, weight, medical history, injection concentration and length of follow-up:

A separate systematic review of knee osteoarthritis trials (Journal of Clinical Orthopaedics and Trauma, May 20, 2021) concluded that prolotherapy appeared to reduce pain and improve function, but warned that many of the studies had a high risk of bias. That qualification matters. Small trials, inconsistent injection techniques, different comparison treatments and inadequate blinding can make a therapy appear more dependable than it really is.

A broader analysis of ten studies involving 750 participants found that pain scores six months to one year after prolotherapy were better than after saline injections or exercise alone (Anesthesia & Pain Medicine, Jan. 2021). Outcomes were not significantly different from those reported with PRP or steroid injections. Those findings are encouraging, but they do not establish that prolotherapy rebuilds cartilage or cures osteoarthritis. At this point, it is more accurate to say that it may reduce pain and improve function for some patients.

Prolotherapy for an Unstable Ankle

The ankle story at the beginning of this article is especially timely. A randomized, triple-blind trial published in the Archives of Physical Medicine and Rehabilitation, July, 2026 included 114 people with chronic ankle instability. Participants received either ultrasound-guided injections of 15 percent dextrose or normal saline into the anterior talofibular ligament. They were treated four times over 16 weeks and followed for one year.

The primary outcome—a patient questionnaire measuring perceived ankle stability—did not differ significantly between the groups. There were, however, two noteworthy findings. People who received dextrose prolotherapy performed better on an objective balance test and experienced fewer repeat ankle sprains during follow-up. No procedure-related adverse events were reported.

The investigators concluded that prolotherapy might be considered for people with chronic ankle instability who have not responded adequately to conservative treatment, or as an addition to exercise rehabilitation.

This trial does not show that prolotherapy should be used immediately after an acute ankle sprain. It studied people with chronic instability and a history of ankle injuries. Nevertheless, the reduction in repeat sprains suggests that prolotherapy may eventually have a role in treating weakened ankle ligaments.

Could Prolotherapy Help Sore Knees?

Knee osteoarthritis remains one of the most commonly studied uses of prolotherapy. People frequently consider it when exercise, weight management, topical treatments and oral pain relievers have not provided enough relief, but they are not ready for knee replacement.

The treatment usually involves several injections spaced weeks apart. Ultrasound guidance may be used to place the solution near the painful joint, tendon or ligament.

Some patients report less pain and better function. Others experience little or no benefit. There is no reliable way to predict who will respond. The American College of Rheumatology and Arthritis Foundation guideline conditionally recommended against prolotherapy for knee or hip osteoarthritis because the number and quality of studies were limited at the time the guideline was developed. More recent studies are encouraging, but they have not completely resolved those concerns.

What Are the Risks of Prolotherapy?

Prolotherapy is often described as low risk, but no injection is entirely harmless. Temporary pain or soreness at the injection site is common. Other possible complications include bruising, bleeding, infection, allergic reaction and injury to nearby nerves or tissues. The location of the injection and the clinician’s training matter a lot!

A review of prolotherapy in primary care concluded that the most common problems were pain and mild bleeding related to the needle itself. The Cleveland Clinic advises patients that the evidence remains inconclusive and that prolotherapy is not an FDA-approved treatment. It also warns that treatment may be expensive and may not work.

People taking anticoagulants or those with an infection, bleeding disorder or certain other medical conditions should discuss the risks carefully with a knowledgeable clinician.

Patients should also ask what is actually being injected. “Prolotherapy” can refer to different solutions and techniques. Evidence involving dextrose should not automatically be applied to every substance marketed under that name.

Prolotherapy and the Problem With NSAIDs

Prolotherapy practitioners often advise patients not to take nonsteroidal anti-inflammatory drugs such as ibuprofen or naproxen around the time of treatment. Their concern is straightforward: if the purpose of the injection is to initiate a healing response, suppressing that response immediately afterward might work at cross-purposes.

This concept remains controversial. People should not stop prescribed medication without discussing it with their healthcare provider.

It does, however, highlight a larger question. Are we sometimes so intent on stopping pain and inflammation that we interfere with the processes needed for recovery?

Inflammation can unquestionably become excessive and destructive. Rheumatoid arthritis, psoriasis and inflammatory bowel disease demonstrate the damage an overactive immune response can cause. But short-term inflammation after exercise or injury is not necessarily the same as chronic inflammation. The early inflammatory phase helps clear damaged cells and coordinates the next stages of tissue repair.

The challenge is not simply to turn inflammation on or off. It is to encourage the right response, in the right place, for the right amount of time.

Prolotherapy and the New Science of Regenerative Therapies

We recently interviewed pain specialist Thomas Buchheit, MD, for our radio show and podcast, Show 1468: Healing Joints and Nerves: The New Science of Regenerative Therapies.

Dr. Buchheit explained that movement can help create the signaling needed for damaged tissue to recover. He also discussed regenerative approaches including prolotherapy, PRP, medicinal signaling cells, autologous conditioned serum and hydrodissection.

One of the most intriguing ideas from that conversation was the distinction between destructive, chronic inflammation and a short-lived inflammatory response that helps initiate healing and resolution.

You can watch and listen to the program/podcast and learn more about these therapies here:

Is Prolotherapy Worth Considering?

Prolotherapy is not a miracle cure. Nor is it pure nonsense.

The evidence is strongest for certain chronic musculoskeletal problems, especially knee osteoarthritis, tendinopathy and possibly chronic ligament instability. Even there, studies are relatively small and treatment methods vary.

It probably makes the most sense for someone who:

• has a clearly diagnosed joint, tendon or ligament problem;
• has not improved sufficiently with appropriate rehabilitation;
• understands that benefit is uncertain;
• can afford a treatment that insurance may not cover; and
• consults a clinician with substantial training in musculoskeletal diagnosis and image-guided injections.

Prolotherapy should not substitute for diagnosing a fracture, torn tendon, infection, inflammatory arthritis or another serious problem.

Nor should injections replace exercise and rehabilitation. The most promising approach may be to combine an appropriate regenerative treatment with carefully supervised movement that gradually restores strength, balance and function.

The Bottom Line on Prolotherapy and RICE

The demise of RICE and the renewed interest in prolotherapy reflect the same change in thinking. Inflammation is not always an error that must be stamped out. Under the right circumstances, it may be part of the body’s repair crew.

That does not mean every swollen joint should be heated, every injury should be exercised immediately or every painful knee should be injected with sugar water.

It does mean that healing may require more than simply suppressing pain, swelling and inflammation.

Prolotherapy attempts to stimulate a localized repair response rather than silence it. Some clinical trials suggest that this approach can reduce pain, improve function and possibly decrease repeat ankle sprains. Other research remains inconclusive, and major medical organizations have not embraced it as standard treatment.

For people with persistent joint, tendon or ligament pain, however, prolotherapy may be worth discussing with an experienced sports-medicine or regenerative-medicine specialist.

What Do You Think?

Have you ever undergone prolotherapy for knee arthritis, an injured tendon or an unstable ankle? Did it reduce pain or improve your ability to move?

Have you discovered that gentle movement helped an injury recover more quickly than prolonged rest and ice?

Please share your experience in the comment section below. If you know someone who has sore knees, hips, elbows or ankles, why now share this article? Your support helps keep our radio show/podcast on the air and this newsletter alerting people to a variety of therapeutic options. You can support our work with a donation at this link.