Prolotherapy

Keith A. Scorza

Manik Singh

INTRODUCTION

Overuse injuries remain a constant challenge for the sports medicine physician. Injuries such as chronic tendinopathies are traditionally treated with corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs), although it has been decades since Puddu et al. (22) demonstrated that tendinosis is not an inflammatory condition. Most investigations demonstrate that such treatments provide at best a short-term decrease in pain. With growing concern of complications associated with corticosteroids and NSAIDs, the search for other treatment modalities continues (14).
Proinflammatory therapies (“prolotherapy”) are a subject of growing interest and research. Although not a new concept, prolotherapy is new to the rigors of evidence-based medicine. As such, research is subject to skepticism, and providers are reluctant to adopt these techniques.
Prolotherapy is an injection technique that uses the body’s own inflammation and repair system for treatment of chronic musculoskeletal pain. It is a unique alternative to standard care that can be performed quickly in an outpatient setting. The theoretic basis and state of current evidence regarding prolotherapy are discussed in this chapter.

COMMON USES

Commonly used for chronic musculoskeletal pain; most frequently used for chronic tendinopathies, chronic ligament pain, and chronic back pain.
Growing interest in use for osteoarthritis; may contribute to correcting instabilities that contribute to osteoarthritis.
Case reports additionally claim success in treatment of neck pain, groin pain, and traumatic migraines.

HISTORICAL PERSPECTIVES

Hippocratic treatises suggested the utilization of scar tissue to add stability to joints, advising the use of a “hot poker” as treatment for recurrent dislocating shoulders.
During the 1800s, sclerosing agents were used for treatment of varicose veins, hemorrhoids, and nonsurgical hernias.
Prolotherapy was first described in modern literature by Dr. Louis Schultz (30).
- Injected sodium psylliate into painful temporomandibular joints and reported effectiveness for treatment of chronic pain.
- Performed animal studies revealing soft tissue fibrosis within 4-6 days after injections, suggesting that agents might stabilize joints by tightening ligaments.
The term “prolotherapy” was popularized by Dr. George S. Hackett (11,12).
- Theorized that chronic musculoskeletal pain was secondary to chronic laxity of ligaments and bone-tendon junctions.
- Used the term “prolotherapy” to simplify phrases such as fibroproliferative therapy, proliferant therapy, sclerotherapy, and regenerative injection therapy.
- Term derived from “prolo” meaning offspring and “proliferative” meaning to produce new cells in rapid succession. Dr. Hackett considered prolotherapy the “rehabilitation of an incompetent structure by the generation of new cellular tissue.”
- Published works in 1953 describing use of prolotherapy for treatment of chronic sacroiliac pain on 253 patients over a 14-year period (11).
The current prevalence of physicians practicing prolotherapy is uncertain.
- A 2003 survey of osteopathic physicians identified 95 practitioners in the United States with treatment of approximately 450,000 patients. Only 27% of the surveys were returned; therefore, the prevalence was likely much greater (7).
- A 2006 investigation of prolotherapy side effects identified 314 members of the American Academy of Orthopaedic Medicine listed as performing prolotherapy in the member directory (6).
- A survey of 908 primary care patients using narcotic therapies for chronic musculoskeletal pain revealed that 8.3% of the patients had received prolotherapy treatments in the past, with 5.9% receiving treatment during the previous 12 months (8).

PROLOTHERAPY AGENTS

Traditional Agents

Irritants
- Examples: phenol, guaiacol, tannic acid
- Irritants contain a phenol hydroxyl group that is oxidized to quinine derivatives. Such agents are thought to alkylate surface proteins of cells, either damaging the cell wall or making the cell antigenic. The end result is an initiation of an inflammatory cascade.
Osmotics
- Examples: dextrose, glycerin
- Osmotics are thought to increase extracellular osmotic pressure and, therefore, dehydrate cells at the injection site. This may lead to cell lysis with the release of cell fragments, attraction of granulocytes and macrophages, and a resultant inflammatory cascade.
Chemotactics
- Examples: sodium morrhuate, polidocanol
- Chemotactics are thought to be direct precursors of and may undergo conversion into inflammatory mediators (e.g., prostaglandins, leukotrienes, thromboxanes).
Particulates
- Example: pumice flour
- Particulates are thought to attract macrophages to the injection site, initiating an inflammatory cascade.

Modern Agents (see Chapter 73, Platelet-Rich Plasma Therapy and Autologous Blood)

Specific growth factors, whole blood, platelet-rich plasma
- Modern agents use specific growth factors or carriers of growth factors (e.g., platelets) to initiate an inflammatory cascade (2,9,28).

MECHANISM OF ACTION

The mechanism of action of prolotherapy is not fully understood.
Prolotherapy agents are proposed to either attract inflammatory mediators or induce the release of growth factors to induce an inflammatory reaction. Such reaction is the first stage of the healing process and theoretically promotes repair of degenerated structures. See “Prolotherapy Agents” section for individual mechanisms of action.
Other mechanisms not involving inflammatory responses have been suggested.
- Macrophages responding to particulate agents may secrete a polypeptide promoting fibroplasia.
- Irritant agents may cause neurolysis/denervation of nociceptive fibers.
- Injections with significant volume may result in lysis of connective tissue adhesions.