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The New Age of Prolotherapy

In addition to traditional prolotherapy, platelet-rich plasma and stem cells are also available to enhance healing of musculoskeletal injuries and mitigation of pain.
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There are also reports of less than four to five times concentration being effective, but it is possible that is a function of a higher starting baseline of platelets (i.e., the patient had a baseline of 400, thus a 2 or 3 fold expansion seemed to work well). It is also possible that studies which show the lack of effectiveness of PRP are in patients whose baseline platelet count is normally low, such that one million platelets/mL was not obtained.

Prolotherapy Versus PRP
The use of hyperosmolar dextrose (prolotherapy) has been shown to increase platelet-derived growth factor expression and up-regulate multiple mitogenic factors72 that may act as signaling mechanisms in tendon repair. Saline prolotherapy can have a similar effect.73 An interesting study published in the January 2010 JAMA compared PRP versus saline injection (basically saline prolotherapy) for chronic Achilles tendinopathy. Both groups improved “significantly” and the authors conclude there was no statistical difference between the improvement of both groups.74 Therefore, both PRP and prolotherapy have been shown to stimulate natural healing75 and both can be effective and both should be considered in the treatment plan for connective tissue repair. However, PRP may be more appropriate in some cases. When PRP is used as a prolotherapy “formula” for chronic or longstanding injuries, the PRP increases the initial healing factors and thereby the rate of healing. The prolotherapy itself (irritation, needle microtrauma) is what is “tricking” the body into initiating repair at these long forgotten sites as well as the PRP, itself, which also acts as an “irritating solution.” This is especially important with chronic injuries, degeneration and severe tendonosis, where the body has stopped recognizing that area as “something to repair.” In these cases, PRP may be more appropriate, however this determination should be made on an individual basis. PRP can also be used preferentially over dextrose prolotherapy in the case of a tendon sheath or muscle injury—areas occasionally but not typically treated with dextrose prolotherapy where the focus is the fibro-osseous junction (enthesis).76 It can also be used preferentially over dextrose prolotherapy because of patient preference (see Figure 8).

Whole Blood Injections vs PRP
Even before PRP, it was not unheard of to use whole blood as a prolotherapy solution, especially where the patient was hypersensitive to other formulas.77 A 2006 study in the British Journal of Sports Medicine studied the use of whole blood with “needling”(irritation such as with prolotherapy) and concluded that the use of autologous blood injection, combined with dry needling, “appears to be an effective treatment for medial epicondylitis.”78 Another study in that same journal in 2009 compared injections using whole blood, dextrose prolotherapy, platelet rich plasma and polidocanol (a sclerosing agent), and concluded that there is evidence to support the use of each of these agents in the treatment of connective tissue damage.79 However, there are only three known studies using whole blood, all of which were prospective case series without controls and small patient numbers.80-82 PRP studies, on the other hand, are growing not only in number, but also in quality.83,84 When examining the physiology of how activated platelets signal repair cells, it seems logical that using PRP (with higher levels of platelets per unit volume) be more effective than autologous blood although no study has yet directly compared the two.85

Whole Blood Injections Versus PRP
Even before PRP, it was not unheard of to use whole blood as a prolotherapy solution, especially where the patient was hypersensitive to other formulas.77 A 2006 study in the British Journal of Sports Medicine studied the use of whole blood with “needling”(irritation such as with prolotherapy) and concluded that the use of autologous blood injection, combined with dry needling, “appears to be an effective treatment for medial epicondylitis.”78 Another study in that same journal in 2009 compared injections using whole blood, dextrose prolotherapy, platelet rich plasma and polidocanol (a sclerosing agent), and concluded that there is evidence to support the use of each of these agents in the treatment of connective tissue damage.79 However, there are only three known studies using whole blood, all of which were prospective case series without controls and small patient numbers.80-82 PRP studies, on the other hand, are growing not only in number, but also in quality.83,84 When examining the physiology of how activated platelets signal repair cells, it seems logical that using PRP (with higher levels of platelets per unit volume) be more effective than autologous blood although no study has yet directly compared the two.85

Cortisone vs PRP
The use of cortisone in musculoskeletal injuries is controversial and the subject of various studies over the years. In February 2010, researchers in the Netherlands published the results of a well designed, two year randomized controlled blinded trial with a significant test group of 100 patients, comparing corticosteroid use to an injection of concentrated platelet rich plasma86 without ultrasound guidance. The PRP injection was given to the lateral epicondyle area of “maximum tenderness,” and a “peppering” technique was used in order to activate the thrombin release from the tendon—in this case endogenous thrombin is the activator for the injected platelet growth factors. The researchers indicate the importance of the “inflammation” phase *the first two days post treatment) during which there is a migration of macrophages to the injured tissue site. Macrophages release additional growth factors,87 and there is increased collagen synthesis on days three to five. The conclusion of the Netherlands study was that “PRP reduces pain and significantly increases function, exceeding the effect of the corticosteroid injection.”88

Safety Issues
Like prolotherapy, PRP therapy has low risk and few side effects. Concerns such as hyperplasia have been raised regarding the use of growth factors, however there have been no documented cases of carcinogenesis, hyperplasia, or tumor growth associated with the use of autologous PRP.89 PRP growth factors never enter the cell or its nucleus and act through the stimulation of external cell membrane receptors of adult mesenchymal stem cells, fibroblasts, endothelial cells, osteoblasts, and epidermal cells.90 This binding stimulates expression of a normal gene repair sequence, causing normal healing—only much faster. Therefore PRP has no ability to induce tumor formation.91 Also, because it is an autologous sample, the risk of allergy or infectious disease is considered negligible.92 Evidence also exists in studies that PRP may have an antibacterial effect.93

Last updated on: May 11, 2015
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