New Compound That Acts On Peripheral Receptors May Be Promising Treatment For Some Nerve Pain

The scientists hope this approach may lead to the development of pain-relief drugs that lack the debilitating central nervous system side effects limiting the effectiveness of currently available pharmaceuticals.

"Chronic pain is one of the most significant disease states affecting Americans, in terms of economic and social impacts," says Dr. Nora D. Volkow, Director of the National Institute on Drug Abuse. "And, unfortunately, therapeutic options for the treatment of chronic pain are inadequate, partly because a number of drugs that can be used to treat pain have unpleasant side effects that limit their effectiveness, and partly because some of them have the potential for addiction and abuse."

The study, funded by NIDA, part of the National Institutes of Health, will be published online the week of August 11 in the Proceedings of the National Academy of Sciences.

Dr. T. Philip Malan, Jr., of the University of Arizona, Dr. Alexandros Makriyannis, of the University of Connecticut, and their colleagues, studied the activity of a new compound called AM1241, which acts on CB2 cannabinoid receptors. "This is one of the two types of receptors on which THC, the active ingredient in marijuana, acts," Dr. Malan says. "The CB2 receptors are in peripheral sites with immune functions, while the CB1 receptors are in the central nervous system — the brain and spinal cord. The beauty of having a compound that acts on the CB2 receptors is that you can get pain relief without the central nervous system side effects of THC, such as sleepiness and anxiety."

The scientists tested the chemical on mice and rats with neuropathic pain, a complex chronic pain state resulting from nerve injury or disease. They found that this compound increased the ability of the animals to withstand chronic pain that mirrored human models of neuropathic pain.

"Although this is far from being in clinical trials in humans, any new avenue to treat pain is a very positive step," Dr. Malan says. "Almost 6 million people in the United States may experience neuropathic pain. At almost any given time, about 1 person in 4 is experiencing some type of pain and about 1 person in 8 has some type of chronic pain. Pain costs the U.S. economy $120 billion to $180 billion per year. Even though we have therapies, many people continue to experience pain despite receiving treatment. This may be partly because the side effects of many of the drugs we can use prevent patients from using the dose that provides the most intense relief."

The next step, he says, is to test this compound in animals to assess its potential toxicity. "We don't even know how it works. It may act on peripheral nerves, but CB2 receptors have not yet been found there; it may act in some way to inhibit the release of chemicals like prostaglandins from immune cells that increase sensitivity to pain; or they may cause immune system cells to release substances that block the pain response."

AM 1241 was developed by Dr. Makriyannis.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov.