The New Age of Prolotherapy
We live in a technological age. With technology comes growth and enhancement of techniques and prolotherapy is no exception. In the March 2010 issue of the Mayo Clinic Health Letter, the authors talk about a new technique involving the injection of platelet rich plasma (PRP) into tendons.1 Quietly working its way through orthopaedic and sports medicine circles and disguised as a “new” treatment, PRP itself has been around since at least the early 1990s2 in surgical and dental applications, but only recently in the musculoskeletal arena. When used to treat injured tendons, ligaments or joints, PRP is simply a modern version of prolotherapy.3 Almost exactly five years ago, in the April 2005 issue of the Mayo Clinic Health Letter, the authors endorse prolotherapy and write: “In the case of chronic ligament or tendon pain that hasn’t responded to more conservative treatments such as prescribed exercise and physical therapy, prolotherapy may be helpful.”4
Now the Mayo Clinic is endorsing PRP, the “new” prolotherapy, for musculoskeletal injuries. In addition to PRP, stem cell joint injections are being used in recalcitrant cases of joint dysfunction—utilizing both bone marrow and fat tissue as stem cell repositories.5 Musculoskeletal ultrasound is also now available and gaining popularity for use in office diagnosis and guidance (notwithstanding the learning curve required for physician proficiency). This article explores these new developments and what this means for the field of prolotherapy and regenerative medicine.
Review of Prolotherapy
Introduced in the 1930s, prolotherapy is a method of injection treatment designed to stimulate healing.6 A recent definition is “the injection of growth factors or growth factor production stimulants to grow normal cells or tissue.”7 prolotherapy owes its origins to the innovation of Dr. Earl Gedney, an osteopathic physician and surgeon. In the early 1930s, Dr. Gedney caught his thumb in closing surgical suite doors thereby stretching the joint and causing severe pain and instability. After being told by his colleagues that nothing could be done for his condition and that his surgical career was over, Gedney did his own research and decided to “be his own doctor.” He knew of a group of doctors called “herniologists” that used irritating solutions to stimulate the repair of the distended connective tissue ring in hernias. He extrapolated this knowledge to inject his injured thumb and was able to fully rehabilitate it.8
In 1937, Gedney published “The Hypermobile Joint,”9 the first known article about prolotherapy (then called “sclerotherapy”) in the medical literature. The 1937 article gave a preliminary protocol and two case reports—one of a patient with knee pain and another with low back pain—with both successfully treated with this method. Gedney followed up this paper with a presentation at the February 1938 meeting of the Osteopathic Clinical Society of Philadelphia which outlined the technique.10 The solutions used then (and now) are primarily dextrose-based, although other formulas are used and can be effective.11 Prolotherapy is practiced by physicians in the U.S. and worldwide, has been shown effective in treating many musculoskeletal conditions—such as tendinopathies, ligament sprains, back and neck pain, tennis/golfers elbow, ankle pain, joint laxity and instability, plantar fasciitis, shoulder, knee pain and other joint pain.12
How Prolotherapy Works
Prolotherapy works by causing a temporary, low grade inflammation at the injection site, activating fibroblasts to the area, which, in turn, synthesize precursors to mature collagen and thus reinforce connective tissue.2 It has been well documented that direct exposure of fibroblasts to growth factors (either endogenous or exogenous) causes new cell growth and collagen deposition.13-17 Inflammation creates secondary growth factor elevation.2 The inflammatory stimulus of prolotherapy raises the level of growth factors to resume or initiate a new connective tissue repair sequence which had prematurely aborted or never started.2 Animal biopsy studies show ligament thickening, enlargement of the tendinosseous junction, and strengthening of the tendon or ligament after prolotherapy injections.18,19
Platelet Rich Plasma (PRP) Therapy
Platelet rich plasma (PRP) therapy, like prolotherapy, is a method of injection designed to stimulate healing. “Platelet rich plasma” is defined as “autologous blood with concentrations of platelets above baseline levels,”20 “which contains at least seven growth factors.”21 Cell ratios in normal blood contain only 6% platelets, however, in PRP, there is a concentration of 94% platelets (see Figures 1 and 2).22 Platelets contain a number of proteins, cytokines and other bioactive factors that initiate and regulate basic aspects of natural wound healing.23 Circulating platelets secrete growth factors, such as platelet-derived growth factor (stimulates cell replication, angiogenesis), vascular endothelial growth factor (angiogenesis), fibroblast growth factor (proliferation of myoblasts and angiogenesis), and insulin-like growth factor-1 (mediates growth and repair of skeletal muscle), among others.24 Enhanced healing is possible when platelet concentration is increased with PRP.25 Activated platelets “signal” to distant repair cells, including adult stem cells, to come to the injury site (see Figure 3). Increasing the volume of platelets accordingly increases the subsequent influx of repair and stem cells.26 Because the concentrated platelets are suspended in a small volume of plasma, the three plasma proteins fibrin, fibronectin, and vitronectin contribute to a repair matrix.27 You could compare dextrose prolotherapy and PRP this way: prolotherapy is like planting seeds in a garden; PRP therapy is planting seeds with fertilizer.
History of Platelet Rich Plasma Therapy
Beginning in the 1990s and continuing until now, “growth factors” have been a hot topic in the medical world. It is clear that growth factors play a pivotal role in all types of wound healing.28 Investigation into the use of PRP has been reported as early as the 1970s,29 but the necessary equipment was large, expensive ($40,000 in 1996), and required a large quantity of a patients blood (450 cc) and therefore limited to the operating room for large scale surgeries.30 Starting in the early 1990s, multiple reports and studies in maxillofacial dental, periodontal surgery,31,32 cosmetic surgery,33 and skin grafting showed dramatically improved healing with PRP (see Figures 4 and 5).