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9 Articles in Volume 10, Issue #4
Chaos (Nonlinear Dynamics) and Migraine
Enhancement of Nerve Regeneration by Therapeutic Laser
Functional Capacity Evaluation (FCE)
Making Practical Sense of Cytochrome P450
Non-pharmacologic Treatment of Shingles
Pain, Neurotechnology, and the Treatment-enhancement Debate
The New Age of Prolotherapy
Treating Myofacial and Other Idiopathic Head and Neck Pain
Treatment of Painful Cutaneous Wounds

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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In the early 2000s, the use of PRP expanded into orthopedics to augment healing in bone grafts and fractures. Success there encouraged its use in sports medicine for connective tissue repair. Mishra and Pavelko, associated with Stanford University, published the first human study supporting the use of PRP for chronic tendon problems in 2006.34 This study reported a 93% reduction in pain at two year followup. Then, in 2008, Pittsburgh Steelers’ wide receiver, Hines Ward, received PRP for a knee medial collateral ligament sprain, and the Steelers went on to win SuperBowl XLII. Ward credited PRP for his ability to play in that game and his success with this treatment was discussed on national television.35

Since then, other high profile athletes—such as Takashi Saito, closing pitcher for the L.A. Dodgers, and golfer Tiger Woods—credit PRP for helping them return to their sport.36 PRP continues to gain wider acceptance in the sports world with studies continuing to validate the use of PRP for ligament and tendon injuries,37 knee osteoarthritis,38 degenerative knee cartilage,39 chronic elbow tendonosis,40 muscle strain41 and tears,42 jumpers knee,43 plantar fasciitis44 and rotator cuff tendinopathy45—albeit some skeptics and controversy remains.46,47

As the use of PRP has grown, the demand and availability for smaller, more portable and affordable machines has also grown. There are now several available models which allow the physician to create PRP from a small sample of a patients blood in the office setting (see Figure 6).48 Machines are very affordable and many companies offer a complimentary machine with a minimum purchase of PRP preparation kits over a period of time. However, not all marketed PRP devices are equal; they vary in quantity of blood required, platelet concentration, viability and number of spin cycles.49 Harvest Technologies was one of the first PRP devices to gain FDA approval.50 This system uses a floating shelf technology which preserves the viability of platelets until use. In his 2005 text, Marx rated the PReP unit by Harvest Technologies, along with PCCS by Implant Innovations, as the two most effective and practical PRP devices for physician office use, outpatient surgery centers, and wound care center treatment.51

Creation and Activation of PRP
A small amount of the patients blood is drawn (20-120 cc) into a syringe with a small amount of citrate (an anti-clotting agent) then typically spun for about 15 minutes in a special centrifugation system that separates the platelets, blood, and plasma. The plasma-poor layer is then drained off and the “buffy coat” plasma layer extracted along with a small amount of plasma and red cells. In the surgical setting, PRP is activated by the surgeon mixing in calcium chloride and/or thrombin to make a gel-like graft and then placing it where he/she wants accelerated healing. Type I collagen has also been found to be effective in activating and creating a PRP graft.52 In 2006, Murray et al demonstrated successful increase in healing of a central anterior cruciate ligament (ACL) defect in a canine ACL using a collagen-platelet rich plasma matrix graft.53 In some musculoskeletal studies, a 10% solution of calcium chloride is added to the PRP just prior to injection54,55 or is injected simultaneously via another syringe into the area being injected with PRP. Most commonly, however, connective tissue injections are given into the site where repair is needed without any additive. In that case, activation occurs by exposure to tendon-derived collagen released by the injured tissue which is being treated.56,57 “Peppering” the tissue during injection with the needle tip can help ensure endogenous thrombin release needed for activation.

Growth Factors in PRP Stimulate Repair
Growth factors present in granules are released when platelets are activated (see Figure 7).58 After activation, secretion of growth factors begins within 10 minutes. The viability of the platelets and continued release of growth factors into the tissue continues for seven days.59 Meantime, the platelets stimulate the influx of macrophages,60 stem cells and other repair cells, as discussed previously. Microtrauma created by the injection itself also stimulates influx of macrophages and growth factors as in the case of dextrose prolotherapy. Once the platelets die (average life span 7-10 days), the macro-phages continue wound healing regulation by secreting some of the same growth factors as the platelets did, as well as others.61 The amount of initial platelets present in the wound determines the rate of wound healing and explains why PRP used during a surgical procedure speeds recovery.62 This may be because PRP has a strong effect in the early phase of healing.63 Use of a “matrix” to hold the PRP material has been used—especially in the case of a large defect.

Optimum Platelet Concentration Level for PRP
Outpatient PRP preparation systems exist with the ability to concentrate platelets from two to eight times.64 There is some controversy about what the “optimum” platelet concentration should be, but a level of at least 1 million platelets per mL appears to be the “magic number.” Since the average patients platelet count is 200,000 +/- 75, a four to five times concentration appears to be the desired level.65,66 When levels are in the 5x range, the influx of adult stem cells has been noted to increase by over 200%.67 In 2008, Kajikawa et al concluded that PRP enhances the initial mobilization of “circulation-derived cells” in the early stage of tendon healing. “Circulation-derived cells” are defined as mesenchymal stem cells that have the potential to differentiate into reparative fibroblasts or tenocytes as well as macrophages.68 Under normal circumstances, circulation-derived cells last only a short time after tendon injury.69 The authors suggest this as one of the main reasons for the known low healing ability of injured tendons. If the circulation derived cells could be activated and their time-dependant decrease stalled with PRP, then the wounded tendon could more fully heal. This study found an increase in the circulation-derived cells with the PRP group, as well as increased production of types I and III collagen in the PRP group versus control.70 This finding of additional fibroblast proliferation and type I collagen production enhanced by increasing platelet concentrations concur with an earlier study by Lui et al.71 This provides evidence that PRP stimulates the chemotactic migration of human mesenchymal stem cells to the injury site in a dose-dependent manner—i.e., the more concentrated the platelets, the more stimulation.

Last updated on: May 11, 2015
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