Prolotherapy is still little known in Italy; is an acronym that derives from proliferation therapy (prolo-therapy), coined in the fifties by G. Hackett, an American orthopedic surgeon. It is an established and widespread infiltrative therapy in the United States, especially in the medical-sports field, included in the evidence-based protocols for the treatment of connective tissue pathologies (tendinopathies and non-surgical ligament injuries). Prolotherapy is an injection method suited for tendinopathies, in the forms characterized by tendinosis and is very effective when there are no sub-total or full-thickness ruptures for which the indication remains, of course, surgical. In cases of tendinosis of any district, even associated with partial ruptures, very satisfactory results can be obtained (both from the functional and the pain point of view) and it is also a very good treatment of instabilities due to first and second degree injuries on ligaments.
What has definitely changed today is the therapy used soon after the trauma. In the specialist field, the intervention with anti-inflammatories drugs is less and less used, as well as infiltrations with corticosteroids: in 1998, in fact, a review of the literature had shown a low level of effectiveness in the use of NSAIDs in the treatment of tendinopathies and one more recent study, made in 2006, shows that simple physical activity and in particular eccentric contraction exercises is superior, in a common pathology such as epicondylitis, compared to infiltration with steroids.
Other studies confirm that corticosteroid therapy, in counteracting the inflammatory process, induces a decrease, even at low dosages, of the vitality of tenocytes which lose the ability to deposit collagen. Already in 2002 important authors such as Maffulli claimed the need to change the terminology on the basis of etiopathological discoveries and to abandon the habit of calling these tendinitis pathologies, since etiopathogenesis sees a prevalence of degenerative and non-inflammatory phenomena: in this sense it is therefore more correct to call them tendinosis.
Prolotherapy has the advantage of stimulating tissue healing through the use of different substances. In Italy (on the indication of the Italian Society of Prolotherapy) a glucose solution in concentrations going from 15 to 25% (added with lidocaine to 1%) is mainly used with the aim of stimulating the tenocyte to perform its physiological function. What is still little considered, in addition to the classic inflammatory phase, is the role of the neurogenic inflammation phase, which interferes with the healing process and justifies the typical symptomatology of these patients, especially when the pathology become chronic owing to incomplete healing.
It is certainly important to act on tissue regeneration and modulate neurogenic inflammation. In vitro studies have demonstrated the ability of dextrose to stimulate the release of growth factors by mesenchymal cells, activating the genes that code for growth factors through a chemical-physical signal transduction mechanism within 20 minutes of exposure to glucose concentrations of 0.45% (in physiological conditions the basal levels are around 0.1%).
Furthermore, a secondary but little-known effect of dextrose and glucose is that of modulating the action of vanilloid receptors (TPRV1) which are responsible for neurogenic inflammation, inhibiting the nociceptive action of neuropeptides such as substance P. There are no precise indications regarding the frequency of infiltrations, but the physiological times of tissue remodeling must be respected; it is therefore necessary to intersperse them for at least two to three weeks.
Clinical studies and case reports on prolotherapy are available in various specialist journals and on scientific search engines such as PubMed.
There are studies conducted on animal models that confirm the trophic effect on tendons, while randomized clinical trials against placebo, which allow to provide a high level of evidence, exist only for some tendinopathies. In particular, there are several double-blind studies on epicondylitis (fig. 1 a-b) and indicate that prolotherapy should be preferred to corticosteroid treatment. Furthermore, there is a sufficient level of evidence that supports its use for yarrow tendinopathy and plantar fasciitis.

We can therefore say that prolotherapy is proposed as a valid therapeutic option in the infiltrative treatment of tendinopathies difficult to solve with traditional methods; it is safe, unlike corticosteroids it has no side effects (such as the atrophy effect and local immunosuppression) and also does not interfere with the potential surgical act.
In conclusion, according to current literature, the use of NSAIDs in the acute algic phase should be avoided or limited by preferring an analgesia control with drugs such as acetaminophen, tramadol and analogues. If you opt for regenerative therapy, integration with nitric oxide precursors and with eccentric contraction exercises starting from week II-III is certainly useful, in conjunction with the phase of tissue remodeling of collagen.
Finally, care must be taken not to return to physical activity when the tendon is not yet ready to bear certain biomechanical loads and make this decision only after a rigorous clinical examination and possibly with the support of ultrasound imaging.