Funding for 2008

Low-Dose Naltrexone for the Treatment of Fibromyalgia

Principal Investigators: Jarred Younger, Ph.D., and Sean Mackey, M.D., Ph.D.
Stanford University, Palo Alto, California
Award Amount: $50,000

Relief from chronic pain is difficult to achieve, and this may be partly explained by the fact that there are two targets: the neurons and the nearby glial cells. All drugs to date were designed to work on the neurons, but some of them have the ability to alter the function of the glial cells. Naltrexone is one of them.

Under normal circumstances, the glial cells provide the neurons with nutrients and are silent in the role of pain transmission. However, many glia-activating substances are elevated in the spinal fluid of people with fibromyalgia, such as substance P, nerve growth factor, and even opioids produced by the body. Activated glial cells produce a surge of pro-inflammatory cytokines, including interferon, tumor necrosis factor, and various interleukins, which then sensitize the nerve fibers. The goal of the study is to reduce the sensitization of the pain-transmitting nerve fibers that are believe to be involved in fibromyalgia.

AFSA has funded Younger and Mackey to test a novel treatment option of low-dose naltrexone to relieve the symptoms of fibromyalgia. In normal doses (around 50 mg), the drug blocks pain-relieving chemicals such as endorphins (the body’s own opioids). This would certainly not be desirable for people with fibromyalgia, but the drug also blocks the activation of the glial cells so they do not produce pain-promoting substances. The key is to use a smaller dose of naltrexone (3-4.5 mg), which may still “chill out” the glial cells while not appreciably interfering with the body’s own opioid pain relievers.

The ability of naltrexone to shut down the pain-promoting activities of the glial cells was recently discovered and appears to be safe. It has been tested in small trials for the treatment of Crohn’s disease and multiple sclerosis pain. Now it will be determined if the drug can benefit individuals with fibromyalgia.

Forty people with fibromyalgia will participate in the trial. For part of the study, these individuals will receive low-dose naltrexone every night before bedtime. For another part of the study, they will receive an inactive placebo substance. Neither the participants nor the researchers will know what the participants are receiving until the study is completed. In a research plan called a crossover design, participants will start on either the drug or placebo, and will then switch to the other substance. A two-week period will separate the conditions so the drug can leave the body.

Participants will fill out a short questionnaire every night to chart their pain levels, sleep quality, physical activity, mood, fatigue and other aspects related to fibromyalgia. These symptom values will be collected on hand-held computers (e.g., palm pilots) and will allow the researchers to conduct very powerful tests of the drug’s effectiveness. For example, an analysis of the data may show that daily fatigue and pain are both reduced when a person is taking the drug. The method will also allow the researchers to identify which symptoms improve first. In addition, participants will visit the Stanford Pain Clinic Lab every two weeks to undergo more thorough and objective tests of pain sensitivity.

Finally, it is well-known that not all people will react well to a certain drug. Participants will undergo a variety of tests at the beginning of the study to determine the characteristics of the patients who reap the most relief from the medication. This will help physicians determine which individuals should receive the medication.