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Regenerative Injection Therapy

  1. Prolotherapy
  2. Platelet-Rich Plasma Therapy


Prolotherapy is an evidence-based* injection technique that uses inflammation – the body’s natural method of healing – to help heal acute and chronic sprain injuries of ligaments and tendons.

The word, “Prolotherapy”, is derived from the term “proliferative therapy”. The standard technique consists, basically, of injecting small amounts of a dilute solution of Procaine™ and glucose into the injury site. Other substances besides glucose may be used on a case-by-case basis. The proliferant solution irritates the ligament or tendon tissue just enough to cause a very localized inflammatory response at the specific site of the sprain injury.

These injections are often ultrasound guided. The inflammation resulting from the proliferant injection selectively activates the fibroblastic cells of the target ligament or tendon. These stimulated fibroblasts then begin to lay down (or cause the proliferation or regeneration) of new ligament or tendon tissue in the form of newly generated collagen fibers. The regenerated collagen mends the acute or chronic sprain injury – restoring joint function and removing the structural cause for joint pain and disability. Because each ligament and muscle has at least two attachments – proximal and distal – either one or both attachment may need to be treated in order to heal a sprain injury.

Platelet-Rich Plasma (PRP) Therapy is an advanced form of standard Prolotherapy. This newer technique incorporates the collection of the patient’s own platelets and the injection of the Platelet-Rich Plasma into the site of significant ligament or tendon tearing.

These injections are often ultrasound guided.

* Random-Controlled Trial Evidence

The following peer-reviewed journal articles have resulted in healthcare insurance reimbursement for lateral epicondylosis (tennis elbow):

  1. The efficacy of Prolotherapy for lateral epicondylosis: a pilot study. Scarpone, M, et. al. Clinical Journal of Sports Medicine 2008 May;18(3):248-54.
  2. The systematic review of four injection therapies for lateral epicondylosis: Prolotherapye whole blood, and Platelet-Rich Plasma. Rabago D, et al. British Journal of Sports Medicine, 2009 Jan 21.Platelet Rich Plasma Therapy

Platelet Rich Plasma Therapy

Platelet-Rich Plasma (PRP) Therapy is the current state-of-the-science-and-art of Prolotherapy.

Platelet-Rich Plasma Therapy has lately surfaced in the popular press as an excellent approach to treating especially-stubborn tendon sprain injuries. This advanced form of Prolotherapy consists generally of the following steps:

  • Drawing 20 cc of the patient’s blood – usually from the antecubital (anterior elbow) vein just like most laboratory blood draws.
  • Spinning that blood specimen in a specially designed centrifuge that separates off the patient’s own blood platelets suspended in the patient’s plasma.
  • Drawing the resultant 2-3 cc collection of platelet-rich plasma into a regular Prolotherapy syringe.
  • Injecting the Platelet-Rich Plasma directly into a sprained tendon or ligament at the site of the injury.

These injections are often guided by ultrasound imaging to direct the injection to the exact site of the tear.

It was George S. Hackett and his colleagues who began asking in the 1930s how we could better treat and heal chronic sprain injuries.1 Hackett, et. al., reached out to what little was known about wound healing at the time and came up with the pragmatic realization that stimulating natural inflammation could be the answer.

We now know that traumatic wound healing or tissue regeneration occurs in four phases:

  • Inflammatory Phase, which occurs when initially injured, disrupted cells release chemical agents (i.e., so-called “growth factors”) that cause a localized inflammatory reaction. The creating of an inflammatory reaction is the first of a series of cascading events that constitute the entire healing process. Inflammation further releases more growth factors, which, in turn, cause the migration and division of inflammatory cells needed for the phagocytosis of cellular debris, setting the stage for the next phase.

What is a growth factor?

A growth factor is a growth-enhancing peptide or protein that binds to receptors on a cell surface, activating cellular proliferation into more of the same cell form or differentiation (morphing) into another cellular form. In other words, a growth factor is a cell-secreted peptide or protein that promotes or increases (i.e., “up-regulates”) normal cellular functions, such as cell proliferation, differentiation, and tissue repair.2

  • Proliferative Phase, which occurs when new blood vessels form (i.e., angiogenesis) and fibroblasts migrate, proliferate, and begin depositing (regenerating) Type II collagen, resulting in the formation of so-called “granulation tissue.” All of these crucially important events are the direct result of the activity of specific growth factors, many of which are supplied by blood platelets.

What is platelet?

A platelet is a normal cellular component of blood. Like the normal circulating red blood cell (erythrocyte), the platelet has no nucleus. If the normal red blood cell is about eight one-thousandths of an inch in diameter, the normal platelet diameter is about one-twentieth of that. Although very small, the platelet is loaded with various types of “granules” or sac-like secretory vesicles.

Each granule is loaded with an amazing number of different kinds of growth factors. According to the current literature, there are at least 16 major families of growth factors. A platelet alpha granule, alone, contains over 250 different, evolutionarily-related growth factors.3

  • Maturation and Remodeling Phase, which occurs when the Type II collagen fibers convert to Type I collagen and elastin fibers, followed by the formation of collagen fiber cross-linkage – and
  • Re-epithelialization Phase, which occurs when disrupted skin or surrounding connective tissue fascia is closed by scarring or regeneration, respectively.
  • Medical science, even in Hackett’s time, recognized inflammation as the body’s normal process for initiating the healing of the physical disruption of virtually any tissue. Such “physical disruption” might be due to regular wear-and-tear, traumatic injury, infectious disease, or degenerative disease.

Thus, Hackett and colleagues surmised that injecting just a small amount of irritative substance into the location of a chronic ligament or tendon sprain injury should create an inflammatory response, which should ultimately stimulate the healing of the musculoskeletal injury. Today we know that it is not just a matter of hypothetical “should” but, in fact, it all “does” happen.

They chose glucose as a readily available, inexpensive, osmotic irritant – or “proliferant” – solution. As a result, Prolotherapists have been regenerating injured ligament and tendon tissue and healing chronic sprain pain and dysfunction in that fashion ever since. Now, what does all of that Prolotherapy history and basic science have to do with Platelet-Rich Plasma Therapy or PRP?

Platelet-Rich Plasma (PRP) Therapy is a particularly hot topic, nowadays – in the laboratory, the clinic, and on the street. A very recent New York Times (NYT) article describes how two Pittsburg Steelers “used their own blood in an innovative injury treatment before winning the Super Bowl.”4 The article goes on to cite several other sports figures who have also been successfully treated in this fashion. It refers to Platelet-Rich Plasma Therapy as a means of delivering a “growth-factor cocktail” to such injuries as “tennis elbow” or “knee tendin (osis).”

It is gratifying – if not somewhat humorous – that the advocates for this “new” Platelet-Rich Plasma treatment describe how this “nonsurgical” therapy works by using “the body’s own cells to help it heal” – as if Prolotherapists have not been doing exactly the same thing since the mid-1930s. And the same Platelet-Rich Plasma advocates tout their noninvasive technique du jour as providing better cost-effectiveness compared to surgery, thereby making Platelet-Rich Plasma Therapy hugely attractive for preferential insurance reimbursement – while standard Prolotherapy remains non-reimbursed by most healthcare insurance programs!

The truth of the matter is that Prolotherapists have been using the earliest version of Platelet-Rich Plasma Therapy for years – achieving all of Platelet-Rich Plasma Therapy’s basic positive attributes, albeit less potent to some degree but at a very small fraction of the cost.

The NYT article goes on to say that Platelet-Rich Plasma Therapy “has the potential to revolutionize not just sports medicine but all of the orthopedics” – possibly “obviating surgery and shortening rehabilitation.” Isn’t that one reason why Prolotherapists have been calling our style of practice “Orthopedic Medicine”: treating joint injury and dysfunction while protecting our patients, whenever possible, from more invasive, expensive, and potentially debilitating orthopedic surgery by using the nonsurgical, regenerative approach of Prolotherapy?

It is obvious that Platelet-Rich Plasma Therapy is a logically next progression toward perfecting the Hackett technique for repairing extremely recalcitrant, severe ligament and tendon tear injury. And Platelet-Rich Plasma Therapy may be just technically attractive enough to catch the public’s, the physician’s (medical, osteopathic, and surgical), the dentist’s, the veterinarian’s – and the insurance company’s eye – finally!

Rabago, D. et. al., described a systematic review of the efficacy of four therapies for lateral epicondylosis (i.e., “tennis elbow” or sprain injury of the proximal tendon of the radial extensor muscle of the forearm).5 Those four therapies – including Platelet-Rich Plasma Therapy – are, very basically, four different types of therapy delivery systems. Each system delivers a growth factor or other therapeutic agent of some form to the injured tendon.

So, Platelet-Rich Plasma is a unique system for delivering platelets loaded with growth factors.

And, when those 2-3 cc of Platelet-Rich Plasma are injected into the patient’s tendon or ligament injury site, a multitude of growth factors are directly delivered to facilitate the healing of even sizeable musculoskeletal tears.


  1. Hackett GS, Hemwall GA, and Montgomery GA. Ligament and Tendon Relaxation Treated by Prolotherapy. 5th ed. Beulah Land Press, Oak Park, IL, 2002.
  2. The Medical Biochemistry Page.
  3. A free medical knowledge base.
  4. Schwarz A. A promising treatment for athletes, in blood. The New York Times, Sports Section, p A1, Feb 17, 2009.
  5. Rabago D, et al. The systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet rich plasma. British Journal of Sports Medicine. 2009 Jan 21.

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