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All proliferative substances for therapeutic use have in common to stimulate the process of tissue healing. In Italy, 15% glucose is mostly used together with Lidocaine.

The quantity, frequency and choice of the proliferative substance varies according to the location and severity of the pathology: generally the injections take place once every 3 weeks for about 4-6 treatments.

The injections can temporarily accentuate the pain.

The doctor distributes the proliferative substance drop by drop in the ligaments and in their insertion points. Small physical exercises, after infiltrations, help the distribution of the drug, helping the correct orientation of the collagen to be regenerated.


Prolotherapy (injections of proliferating substance) involves the injection of a solution (usually solutions not containing drugs but which exert an osmotic effect) in the human body generally in the tendons or ligaments with the aim of strengthening the weakened connective tissue and thus alleviating musculoskeletal pain.


Prolotherapy must be distinguished from sclerosing therapy: sclerosing therapy consists of the injection of caustic substances into the veins, vascular surgery and dermatology to obtain the resolution of varicose veins and angiomatosis. Prolotherapy consists of the use of injections in the treatment of connective tissue resistance defects and musculoskeletal pain.

Prolotherapy is also called "proliferating therapy" or "tissue regenerative therapy".

In the USA it can be used as an alternative to arthroscopic surgery. In fact, in a double-blind controlled study on the effects of arthroscopic surgery in knee osteoarthritis published in New EJ Of. Med. Published in July 2002, it concluded that patients undergoing arthroscopy did not recover better functionality than patients who received a placebo . Arthroscopic knee surgery actually does not have a preferential indication in osteoarthritis of the knee but is more indicated in cases where a break in the meniscal or patellofemoral cartilage occurs. Prolotherapy is not intended to solve these problems.

There are doctors and surgeons have reported successful anecdotal cases of knee injuries, shoulder dislocations and traumatology typical of golfers (epicondylitis, shoulder sprain, acute low back pain and chronic knee and hip injuries). However, despite these successes, prolotherapy is still not recognized by most doctors who deal with these problems as the treatment of choice in painful musculoskeletal disorders.

In 2005, a Mayo Clinic doctor said that unlike steroid infiltrations - which can provide only temporary relief - prolotherapy improves the biomechanical characteristics of the tissues causing the growth of new connective tissue.

A review by the Cochrane Collaboration on the use of prolotherapy in low back pain stated that "There is conflicting evidence on the effectiveness of proliferating injections in patients with chronic low back pain. If used alone, prolotherapy does not seem to have a significant role in the treatment of chronic low back pain, while if used in combination with other treatments it can provide prolonged relief of pain and disability ". However, there are other studies underway.


Prolotherapy in clinical practice





















Prolotherapy involves the infiltration of an irritant in the area where the connective tissue has been weakened or damaged due to functional overload or trauma.

The solutions that are commonly used are usually dextrose, lidocaine, phenol, glycerin, sodium morrurate or cod liver oil extract. Infiltration is practiced inside the joint capsule or at the point where the tendon or ligament connects to the bone. Sometimes the injections are more than one and the points to be injected can be numerous.

The injected solution causes an inflammatory reaction that stimulates spontaneous healing of the human body and possible healing. The inflammatory reaction that is generated in the body in which the sclerosing solution has been injected can produce a growth of 30-40% of the volume and resistance of the tissues in which the product is injected (in this regard, however, certain scientific demonstrations are scarce ).

Prolotherapy sessions are carried out regularly at time intervals that vary between 2 and six weeks. Many patients receive maintenance sessions at less and less frequent intervals until the treatment is stopped.


History of technology

Injections of irritant solutions had been introduced in the late 1800s in the treatment of abdominal hernias, and in the early 1900s for pain in the temporomandibular joint due to joint laxity. Dr. George Hackett developed his technique for performing these infiltrations in the 1940s. Dr. Gustav Hemwall was another pioneer who started practicing prolotherapy under Hackett's teaching in the early 1950s. In over 40 years of professional activity that ended in the mid-90s he reports that he has treated at least 10,000 people with a 99% success rate in patients with chronic pain.

Indications and guidelines used by doctors who use this technique with positive prognostic indicators

Recurrent hydratum or swelling involving a joint


  • Joint showers or "click" sensation during movement

  • Feeling of sagging of the leg

  • Feeling of leg weakness associated with low back pain

  • Temporary benefit from manipulative therapy with frequent relapses of joint blockage

  • "Trigger points" along the bone or at the tendon insertion

  • Feeling of burning, numbness, pain related to the upper limb or leg with non-metameric distribution

  • Frequent painful episodes localized to the face, head, jaw or ear

  • Local pain and sensitivity along the insertion of the ribs to the spine or front of the chest

  • Spine pain where there is no surgical indication


Medicine based on scientific evidence

A review of the Cochrane association's scientific literature published in January 2004 on the effectiveness of sclerosing infiltrations in adults with low back pain found four controlled clinical trials that measured pain and disability six months after the procedure. These are the conclusions of the research:

"There is conflicting evidence regarding the effectiveness of prolotherapy infiltrations in reducing pain and disability in patients with chronic low back pain. The studies are confused due to the heterogeneity of the samples examined and due to the presence of other therapeutic interventions. There was no evidence that prolotherapy alone is more effective than control injections performed. However, in the presence of multiple therapies, prolotherapy was found to be more effective than control injections. A fortiori it was noted that this was even more true when control injections and multiple therapeutic interventions were controlled simultaneously.

Research has also underlined that after the infiltrative procedure with prolotherapy there is always an increase in pain and stiffness which are however of short duration (this phenomenon is explained by the fact that the substance that is injected has the purpose of causing a short inflammatory response that the natural reparative process begins.

More recently Rebago found that in two randomized trials it was noted that after prolotherapy there was a reduction in pain, an increase in joint movement and an increase in the thickness of the patello-femoral cartilage.


Critical issues

In the US, most insurance companies do not reimburse treatment. In 1999 Medicare refused to include the procedure among the reimbursable treatments for chronic low back pain alleging that a negative opinion was given in the last examination of the procedure performed by the Health Care Financing Administration (HCFA) in 1992. In Italy it is theoretically possible to perform infiltrations within the NHS as there is a specific entry in the National Tariff (infiltration of ligaments and joints) but there are few doctors who know its usefulness and who are able to perform it.


Studies in progress

Osteoarthritis of the knee

A randomized double-blind study on osteoarthritis of the knee is underway. The study aims to determine whether prolotherapy is able to decrease pain and disability in osteoarthritis of the knee. The study is sponsored by the National Center for Complementary and Alternative Medicine (NCCAM).


A randomized double-blind study is underway to determine whether prolotherapy is effective in epicondylitis (tennis elbow).


Links and linked sites

• Prolotherapy.org is a great source of comprehensive articles, diagrams and resources related to prolotherapy

• Prolotherapy.com is a source of information on the non-surgical treatment of ligament injuries

• American Association of Orthopedic Medicine It is the site of a non-profit organization that promotes prolotherapy

www.proloterapia.eu is the site of SIPRO - Italian Society of Prolotherapy


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Prot. 1729 of 07.10.2002

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