What is
Prolotherapy and
What are the Indications 
and Contraindications
for it? K. Dean Reeves, MD

Prolotherapy is injection of any substance that acts as a ‘growth factor,’ that is, which promotes growth of normal cells, tissues, or organs. Injection of the hormone, erythropoietin, to produce red blood cells is widely used, and a number of other substances have been used for treatment of patients with various medical disorders. This discussion focuses on Prolotherapy for musculoskeletal disorders, including arthritis and back pain. 

Non-inflammatory growth factor production methods have been used in the treatment of patients with arthritis. Injection of a sub-inflammatory level of dextrose (10%) in to the joints of patients with knee or finger Osteoarthritis (OA) has been shown to be effective in improving pain or disease severity.1,2,3

Dextrose can create growth without Inflammation. Research on a variety of human cells exposed to as little as 0.3% to 0.6% dextrose (the normal cell has 0.1% dextrose in and around itself) indicates that within minutes to several hours the cells begin to produce growth factors such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGFB), epidermal growth factor (EGF), basic fibroblast growth factor (BFGF), and connective tissue growth factor (CTGF). Note that both fibroblasts and cartilage cells respond to a variety of growth factors, which are often named for the first cell in which they are discovered but usually act on a variety of cells. 

Studies on non-inflammatory dextrose injection show significant findings. The knee OA study (111 knees injected with less than an ounce of dextrose, divided among 3 injections) demonstrated a flexion improvement of 13°, a 65% reduction in knee-buckling, and significantly better effect than placebo (P=0.015).1 The finger OA study was smaller in patient numbers but showed improvement in pain with finger movement compared with placebo (42%treatment group vs. 15%placebo, P = 0.027) and a superior improvement in range of motion (P=00.3) with 3ml of dextrose divided among 3 injections over 6 months.2

Inflammatory Prolotherapy [that is, with dextrose over 10% concentration] is probably less expensive [to study]. However, all double-blind studies of this form [of Prolotherapy] to date had significant limitations. Two studies used multiple treatments concurrently and compared an inflammatory with a non-inflammatory solution, which in itself may affect blinding.

In a third study, the results were in such opposition to all previous results that it raised the possibility of technical flaw(s). Difficulty in reproduction of technique was an issue in all of these studies because they were done with multiple injection sites in patients who had low back pain. In addition, a large-gauge needle was used to inject bony attachments of ligaments, and irritation of structures by a needle has potential therapeutic effect on its own [apart from what is then injected].

Because the primary pathology in sprain/strain injuries is in connective tissue, with secondary trigger points in muscle, correcting the primary pathology requires injection of the connective tissue. In arthritis, there is much to learn about the balance of disrepair forces vs. growth factors, but stimulation of growth factors has much to offer meantime. Studies of non-inflammatory prolotherapy show probable benefit in OA and possible benefit in Ligament laxity. In addition, physicians performing acupuncture or muscle triggerpoint injection generally find prolotherapy more potent in managing chronic pain. [Stronger still can be the clinical effect of combining prolotherapy with triggerpoint injection.]

To learn prolotherapy, a physician interested in sports medicine essentially must learn how to locate the pain-producing lesion zones in ligaments and tendons and how to inject them. When this skill is mastered, the physician can keep up with advances in available proliferant solutions. [Currently four are in common use worldwide.] What the physician injects will probably change as the literature progresses and may include different growth factors or growth factor stimulants or inflammatory agents.

Prolotherapy is controversial because only a few hundred physicians are currently known to have identified themselves as practicing this in the USA, and because most physicians often use an antiquated definition of the word, such as “inflammatory injection to create growth and repair.” In reality, many non-inflammatory substances are capable of creating a rise in growth factors sufficient to cause proliferation of cells or tissues. Injection of substances to cause or create growth of cells is currently being used in all major hospitals in the United States, whether or not they call it Prolotherapy.

1. Reeves KD Hassanein K Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. Alt Ther Hlth Med 2000;6(2):37-46

2. Reeves KD Hassanein K Randomized, prospective, placebo-controlled double-blind study on dextrose prolotherapy for osteoarthritic thumb and finger (dip, pip, and trapeziometacarpal) joints: evidence of clinical efficacy Jnl Alt Compl Med 2000 6(4): (311-320)

3. Reeves KD Prolotherapy: Basic science, clinical studies, and technique. In Lennard TA(Ed). Pain procedures in clinical practice. (2nd Ed.) Philadelphia; Hanley and Belfus;2000:172-190.

The Journal of Prolotherapy

Prolotherapy Research at
The Journal of Prolotherapy