Prolotherapy (Prolotherapy) is an injection procedure used for some states of chronic musculoskeletal pain. Although it is often presented as a treatment that "restores tissue", the evidence differs according to the disease, the method has no single standard, and the benefit for every kind of tendon, joint, or back problem has not yet been confirmed.

Chronic pain alone does not make a patient suitable for this procedure. Similar symptoms may arise from disease of the tendons, degenerated joints, a fracture, inflammatory disease, irritation of a nerve, pain referred from another position, patterns of movement, a nervous system sensitive to pain, or several factors together. Selection must therefore begin from the diagnosis, the evidence for that disease, reasonable alternatives, medical readiness, and giving consent after receiving information.

What is prolotherapy?

Prolotherapy is the injection of a substance that creates irritation at a particular place, usually dextrose at high concentration, into or around selected structures of the musculoskeletal system. Research uses different concentrations of dextrose, different mixtures, injection sites, methods of guidance by imaging, treatment schedules, and accompanying rehabilitation.

The proposed mechanism is the stimulation of inflammation and of the response of the cells at that particular place, which may have an effect on pain and on the remodelling of the tissue. However, this mechanism is still a hypothesis. Symptoms improving does not prove that the tendon has been created anew or has become stronger. The words "restoring tissue" should therefore not be interpreted as meaning that the anatomy will be returned to normal, or as a guarantee of biological repair.

What does the evidence say?

The most recent review of the evidence by the United States Department of Veterans Affairs (opens in a new tab) found that the results differ according to the state and to the method of comparison. Dextrose prolotherapy may help the function related to pain in the state of abnormality of the tendon at the lateral side of the elbow and in inflamed plantar fascia when compared with saline, but the confidence in the evidence is low. For injection in a degenerated knee joint, it may give very little benefit or none at all when compared with saline. As for shoulder pain from several causes, the evidence is still very uncertain and physical capacity may be worse than with corticosteroid injection. The evidence concerning adverse symptoms that are met infrequently but are important is also still uncertain, because most of the research is small in size and reports the risks inconsistently.

Therefore, a positive result in one disease is not a reason to use it in another disease, and the words "shows a tendency" do not mean it has been proved superior to exercise, standard care, or another kind of injection.

How does prolotherapy differ from other treatments for pain?

Each form of treatment has a different aim. Exercise and adjusting activity aim to increase capability, movement, and the bearing of load. Medicines may reduce the symptoms or the inflammation. Corticosteroid injection may be used to reduce inflammation in the short term in some states. As for nerve blocks, injection around a nerve, hydrodissection, plasma with a high concentration of platelets, and surgery, each has its own reasoning, evidence, risks, and indications.

If prolotherapy is to be considered, it should therefore be chosen from a clearly identified disease, by comparing the evidence for that disease with the other alternatives. It should not be chosen merely because the pain is chronic or because an image has found an abnormality.

How do prolotherapy and hydrodissection differ?

Both are injection procedures, but they have different aims

Prolotherapy

Prolotherapy injects an irritant substance into or around a tendon, a tendon attachment, a joint, or another selected structure, aiming to create a response at that particular place. The clinical benefit and the suitable method are still uncertain for many forms of use.

Hydrodissection

Hydrodissection injects fluid into the layers of the tissue, usually done around a nerve, in order to separate the nerve from the neighbouring tissue. This method cannot by itself prove that the fascia is "tight" or that the nerve is the root cause of the symptoms. The diagnosis, the substance injected, the position, the evidence, and the risks of the procedure must be assessed separately.

The two procedures should not be done together as a routine. More injections may increase the burden and the exposure to risk, without guaranteeing a better result.

The states usually spoken of together with prolotherapy

The following states appear in the research, but having the name of a disease on a list does not mean that it is suitable for the procedure

Abnormality of the tendon at the lateral side of the elbow and inflamed plantar fascia

The review by the United States Department of Veterans Affairs found that it may help the function related to pain when compared with saline, but the evidence has low confidence. Exercise, the management of load, footwear or ergonomics, and other conservative alternatives must still be considered. This result should not be concluded to apply to every kind of tendon disease.

Other kinds of tendon disease

There is research on the rotator cuff tendons, the Achilles tendon, the patellar tendon, and tendons in other positions, but the methods and the results differ. A systematic review and meta-analysis on the subject of tendon disease, fascia, and injury of the ligaments that hold the joints (opens in a new tab) concluded that the evidence overall is still not enough to support a clinical benefit. The diagnosis of the tendon, the degree of tearing, the amount of load, and a suitable rehabilitation programme are still important.

Degenerated knee or hip joint

It should not be explained that prolotherapy reverses joint degeneration or creates new cartilage. The guidelines of the American College of Rheumatology and the Arthritis Foundation (opens in a new tab) have a conditional recommendation against prolotherapy for a degenerated knee or hip joint, because the studies are few, small in size, and differ in method. Shared decision-making should cover the treatments with better evidence and the limitations of the research on injection.

Chronic lower back pain or suspected instability of a joint

Non-specific lower back pain may arise from several structures and several mechanisms, and there is no simple test that proves that "weak ligaments of the spine" are the cause. The Cochrane review (opens in a new tab) found conflicting evidence. Prolotherapy alone was not more effective than a control injection, while work done together with several methods could not separate out the effect of prolotherapy.

Pain in the muscles and the fascia, or symptoms resembling nerve symptoms

Pain in the muscles, tender points, numbness, tingling, or referred pain are not automatically an indication for prolotherapy. Examining the nervous system and assessing a compressed nerve, an abnormal nerve root, pain referred from another position, systemic disease, and other causes may lead to another form of treatment or to urgent assessment.

Who may be considered?

The procedure may be discussed when:

  • The treating practitioner diagnoses a specific disease, not relying on the position of the pain alone
  • The evidence for that disease and the uncertainties have been explained
  • Suitable conservative care has been tried or considered, unless there is a reason it cannot be used
  • The symptoms affect meaningful activities and there are functional goals that can be measured
  • The patient has medical readiness for injection and is able to follow the advice after the procedure
  • There has been discussion of the alternatives, the costs, the burden expected, and the plan for rehabilitation or activity
  • The patient understands that the benefit is still uncertain and that repeated injection is not automatically necessary

These factors support shared decision-making, but cannot predict who will respond.

Who must receive further or urgent assessment first?

The diagnosis should be made clear before choosing to inject, if the structure that is painful is not yet known, if the symptoms are spread over several positions, if there has been surgery or severe injury such that the anatomy has changed, or if there is numbness, weakness, changed sensation, or referred pain that raises suspicion of the nervous system.

Urgent medical assessment may be needed when there has just been a severe injury, when a fracture or a dislocated joint is suspected, when there is fever or illness throughout the body, a hot swollen joint, weakness increasing rapidly, new abnormal control of continence, numbness in the area of the buttocks or the genitals, weight loss of unknown cause, suspicion of cancer, infection, or other serious disease. Prolotherapy should not delay suitable examination or treatment.

The contraindications and the risks of the procedure that must be reviewed

The person carrying out the procedure must follow the guidelines for the substance injected, the position, and the law in the area. Factors that may make it impossible to do or that require the plan to be adjusted are an infection in the body or at the site of injection, allergy to a component, an abnormal bleeding state that has not yet been put right, the use of antiplatelet medicines or anticoagulants, accompanying disease that is still not well controlled, impaired wound healing or immunity, being unable to give consent or to communicate the symptoms, and being unable to follow the care after injection. Patients should not stop their medicines by themselves without consulting the prescriber.

The short-term effects that can be expected may be pain during the injection, a tight pain, a stiff joint, bruising, or a temporary flare-up of the symptoms. Other risks depend on the position and the method, namely bleeding, infection, an allergic reaction or fainting from a vasovagal reaction, injury to nerves, blood vessels, tendons, joints, or other tissue, and if the injection is near the chest a state of air leaking into the pleural cavity may arise. Ultrasound may help in seeing the anatomy and the position of the needle, but cannot rule out all the risks.

Because the information on adverse symptoms is still not complete, the words "natural", "having sugar as a component", or "minimally invasive" should not be used to convey that the procedure has no risk.

Why is a correct diagnosis important?

The assessment should answer:

  1. Which diagnosis best explains the symptoms and the limitations in living?
  2. Have serious or urgent causes been ruled out?
  3. Which treatment has the best evidence and balances benefit, burden, and risk?
  4. Does prolotherapy have a reasonable role supported by evidence in this disease?

The assessment may consist of the health history and the history of the pain, a review of medicines and the history of drug allergy, previous treatment, physical and neurological examination, assessment of daily routines and movement, as well as imaging or laboratory tests when there is an indication. An abnormality in an image may cause no symptoms and must be interpreted together with the symptoms and the test results.

The role of musculoskeletal ultrasound

Musculoskeletal ultrasound gives a real-time image of the tendons, the muscles, the fascia, the nerves, the joints, and the blood vessels in some positions. It may help in examining structures while they move and in guiding the needle to the target while avoiding the structures that can be seen.

Ultrasound cannot show all the causes of pain, confirm that an abnormality is causing the symptoms, prove instability of the tissue, guarantee the position of the needle, or guarantee a clinical result. The training of the user, the target, aseptic technique, and the overall reasoning in the diagnosis are still important.

Rehabilitation and the planning of activity

For many kinds of musculoskeletal disease, graded exercise, the management of load, education, sleep, adjusting work or sport, and overall health are the main treatment, whether or not injection is used. Prolotherapy does not automatically return strength, movement, balance, coordination, confidence, or the ability to work.

Tolerance of load and function

A programme specific to the individual may gradually increase the load suitable for the tendon, the joint, or the area that has a problem. Progression should be adjusted according to the symptoms, the function, the precautions for the tissue, and the goals, not relying on an assumption that after injection a long rest is required or that load can certainly be increased more quickly.

Movement and the control of joints

Training may emphasise strength, the perception of joint position, balance, coordination, technique, or movement where relevant. The result should be measured from meaningful activities, such as working, walking, lifting, exercising, or playing sport, not from a pain score alone.

What should be expected from the plan that is proposed

There is no internationally standard concentration of the substance, position, number of sessions, or interval for prolotherapy. The plan should state the diagnosis, the goals, the substance injected and its components, the qualifications of the person carrying out the procedure, the use of guiding equipment, the alternatives, the care after injection, the costs, the indicators, and the criteria for not injecting again.

Advice on activity and medicines after the procedure must be adjusted to the individual. A doctor should be seen promptly when there is fever, spreading redness, fluid leaking from the wound, severe or increasing pain, new symptoms of weakness or numbness, difficulty breathing, or other abnormal symptoms after injection.

Questions that should be asked before deciding

  • What disease is being treated, and how was it diagnosed?
  • What evidence supports prolotherapy for this disease, and compared with which method?
  • What alternatives are there that do not require injection?
  • Which substance, concentration, volume, and anatomical position are proposed?
  • Who is the person injecting, and what training do they have?
  • Will equipment for guidance by imaging be used, and in what does it help or not help?
  • What are the common and the serious risks of this injection site?
  • How will the benefit be measured, and what are the criteria for stopping?
  • What plan for rehabilitation or activity accompanies it?

Begin from the diagnosis, not from choosing a kind of injection

Prolotherapy may be brought up for discussion in some groups of musculoskeletal disease, but suitability cannot be concluded from chronic pain, tender points, or an image alone. A responsible decision must weigh the diagnosis, the evidence specific to the disease, the uncertainties, the alternatives, the risks of the procedure, the wishes of the patient, and the plan for restoring function. The result of the assessment may indicate that rehabilitation, another method of treatment, further examination, or not injecting is a more suitable choice.