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Prolotherapy, also called proliferation therapy, is an injection-based unproven treatment used in chronic musculoskeletal conditions.


Medical uses

A 2015 review found no evidence that prolotherapy is safe or effective for
Achilles tendinopathy In Greek mythology, Achilles ( ) or Achilleus () was a hero of the Trojan War who was known as being the greatest of all the Greek warriors. The central character in Homer's ''Iliad'', he was the son of the Nereid Thetis and Peleus, king of P ...
, plantar fasciosis, and
Osgood–Schlatter disease Osgood–Schlatter disease (OSD) is inflammation of the patellar ligament at the tibial tuberosity (apophysitis) usually affecting adolescents during growth spurts. It is characterized by a painful bump just below the knee that is worse with act ...
. The quality of the studies was also poor. Another 2015 review assigned a strength of recommendation level A for Achilles tendinopathy and knee
osteoarthritis Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...
and level B for lateral epicondylosis, Osgood–Schlatter disease, and plantar fasciosis. Level A recommendations are based on consistent and good-quality patient-oriented evidence while level B are based on inconsistent or limited-quality patient-oriented evidence.


Low back pain

A 2007
Cochrane review Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes ...
of prolotherapy in adults with chronic low-back pain found unclear evidence of effect. A 2009 review concluded the same for subacute low back pain. A 2015 review found consistent evidence that it does not help in low back pain. There was tentative evidence of benefit when used with other low back pain treatments. Evidence of benefit remains tentative (level B) for dextrose prolotherapy in low back or sacroiliac pain.


Tendinitis

A 2009
systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...
of the efficacy in the treatment of lateral epicondylitis concluded that these therapies may benefit people with lateral epicondylitis, but the evidence was limited. A 2010 review concluded moderate evidence exists to support the use of prolotherapy injections in the management of pain in lateral epicondylitis, and that prolotherapy was no more effective than eccentric exercise in the treatment of Achilles tendinopathy. A 2016 review found a trend towards benefit in 2016 for lateral epicondylitis. A 2017 review found tentative evidence in Achilles tendinopathy. In 2012, a systematic review studying various injection therapies found that prolotherapy and
hyaluronic acid Hyaluronic acid (; abbreviated HA; conjugate base hyaluronate), also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminog ...
injection therapies were more effective than
placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...
when treating lateral epicondylitis. Of the studies evaluated, one of ten
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...
trials, one of five trials for autologous blood injection or
platelet-rich plasma Platelet-rich plasma (PRP), also known as autologous conditioned plasma, is a concentrate of plasma protein derived from whole blood, centrifuged to remove red blood cells but retaining platelets. Though promoted for treating various medical con ...
, one trial of polidocanol, and one trial of prolotherapy met the criteria for low risk of bias. The authors noted that few of the reviewed trials met the criteria for low risk of bias.


Knee osteoarthritis

Tentative evidence of prolotherapy benefit was reported in a 2011 review. One 2017 review found evidence of benefit from low-quality studies. A 2017 review described the evidence as moderate for knee osteoarthritis. A 2016 review found benefit but there was a moderate degree of variability between trials and risk of bias. In 2019, the
American College of Rheumatology The American College of Rheumatology (ACR; until 1985 called American Rheumatism Association) is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocac ...
recommended against prolotherapy for knee osteoarthritis.


Contraindications

Contraindications for patients to receive prolotherapy injections may include: * Local
abscess An abscess is a collection of pus that has built up within the tissue of the body, usually caused by bacterial infection. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pre ...
*
Bleeding disorders Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding ( bleeding diathesis), which may occur s ...
* Patient on
anticoagulant An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...
medication * Known allergy to prolotherapy agent * Acute infections such as
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
*
Septic arthritis Acute septic arthritis, infectious arthritis, suppurative arthritis, pyogenic arthritis, osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typica ...
Relative contraindications include: * Acute
gouty arthritis Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crystals. Pain typica ...
* Acute
fracture Fracture is the appearance of a crack or complete separation of an object or material into two or more pieces under the action of stress (mechanics), stress. The fracture of a solid usually occurs due to the development of certain displacemen ...


Side effects

Patients receiving prolotherapy injections have reported generally mild side effects, including mild pain and irritation at the injection site (often within 72 hours of the injection), numbness at the injection site, or mild bleeding. Pain from prolotherapy injections is temporary and is often treated with
acetaminophen Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
or, in rare cases,
opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...
medications. NSAIDs are not usually recommended due to their counter action to prolotherapy-induced inflammation, but are occasionally used in patients with pain refractory to other methods of pain control. Theoretical adverse events of prolotherapy injection include
lightheadedness Lightheadedness is a common and typically unpleasant sensation of dizziness or a feeling that one may faint. The sensation of lightheadedness can be short-lived, prolonged, or, rarely, recurring. In addition to dizziness, the individual may fee ...
, allergic reactions to the agent used, bruising, infection, or nerve damage.
Allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...
to sodium morrhuate are rare. Rare cases of back pain, neck pain, spinal cord irritation,
pneumothorax A pneumothorax is collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and dyspnea, shortness of breath. In a minority of cases, a one-way valve is ...
, and disc injury have been reported at a rate comparable to that of other spinal injection procedures.


Technique

Prolotherapy involves the injection of an irritant solution into a joint space, weakened ligament, or tendon insertion to relieve pain. Most commonly, hyperosmolar
dextrose Glucose is a sugar with the molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae during photosynthesis from water an ...
(a sugar) is the solution used;
glycerine Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in ...
,
lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia and ventricular fibrillation. When used for local anae ...
(a commonly used
local anesthetic A local anesthetic (LA) is a medication that causes absence of all sensation (including pain) in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensati ...
),
phenol Phenol (also known as carbolic acid, phenolic acid, or benzenol) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile and can catch fire. The molecule consists of a phenyl group () ...
, and sodium morrhuate (a derivative of
cod liver oil Cod liver oil is a dietary supplement derived from liver of Atlantic cod (''Gadus morhua''). As with most fish oils, it contains the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and also vitamin A and vita ...
extract) are other commonly used agents. The injection is administered at joints, ligaments, or tendons where they connect to bone. Prolotherapy treatment sessions are generally given every two to six weeks for several months in a series ranging from three to six or more treatments. Many patients receive treatment at less frequent intervals until treatments are rarely required, if at all.


Terminology and mechanism

The term originated with George S. Hackett, MD, in 1956 in a publication titled "The rehabilitation of an incompetent structure by the generation of new cellular tissue". He applied the term prolotherapy from the words "proli’" (Latin), meaning offspring, and "proliferate", meaning to produce new cells in rapid succession. Although the erroneous term "
sclerotherapy Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations ( vascular malformations) and also malformations of the lymphatic system. A medication is injected into the vessels ...
" was utilized by some in the past to describe this treatment, it is now clear that prolotherapy does not cause scarring. The mechanism of prolotherapy requires further clarification. It is expected to involve a number of mechanisms.


Criticism

Some major
medical insurance Health insurance or medical insurance (also known as medical aid in South Africa) is a type of insurance that covers the whole or a part of the risk of a person incurring medical expenses. As with other types of insurance, risk is shared among m ...
policies view prolotherapy as an investigational or experimental therapy with an inconclusive evidence base. Consequently, they currently do not provide coverage for prolotherapy procedures. Medicare reviewers in 1999 determined at that time that practitioners had not provided "any scientific evidence on which to base a ifferentcoverage decision," and so retained Medicare's current coverage policy to not cover prolotherapy injections for chronic low back pain, but expressed willingness to reconsider if presented with results of "further studies on the benefits of prolotherapy."


History

The concept of creating irritation or injury to stimulate healing has been recorded as early as Roman times when hot needles were poked into the shoulders of injured gladiators. In 1840, French surgeon Alfred-Armand-Louis-Marie Velpeau published a paper detailing how he had injected an iodine solution into a hernia in order to create beneficial inflammation. American surgeon Joseph Pancoast later wrote that he had been performing this procedure (using either iodine or cantharides) since 1836. Another early American practitioner of this method was George Heaton. After World War 1,
sclerotherapy Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations ( vascular malformations) and also malformations of the lymphatic system. A medication is injected into the vessels ...
came to be a common treatment for malformations of
blood vessels Blood vessels are the tubular structures of a circulatory system that transport blood throughout many animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste an ...
and the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lympha ...
. This involved injecting a therapeutic liquid to shrink them. By the late 1920s, this method was used to treat
hernia A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ (anatomy), organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal Devel ...
s. By the late 1930s, it was also used to treat
ligamentous laxity Ligamentous laxity or ligament laxity can appear in a variety of ways and levels of severity. In most people, ligaments (which are the tissues that connect bones to each other) are naturally tight in such a way that the joints are restricted to ...
. In the 1950s, George S. Hackett, a general surgeon in the United States, began performing injections of irritant solutions in an effort to repair
joints A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...
and hernias. In 1955, Gustav Anders Hemwall became acquainted with George Hackett at an
American Medical Association The American Medical Association (AMA) is an American professional association and lobbying group of physicians and medical students. This medical association was founded in 1847 and is headquartered in Chicago, Illinois. Membership was 271,660 ...
meeting and started practicing the technique. Hackett coined the term "prolotherapy" for the practice, a very early appearance being in his 1956 book ''Ligament and Tendon Relaxation (Skeletal Disability) Treated by Prolotherapy (Fibro-Osseus Proliferation)''.


References

{{Reflist, 30em Musculoskeletal system Orthopedic surgical procedures Regenerative biomedicine Alternative medical treatments