CAMBRIDGE, Mass. — New information on a cellular messenger may lead to powerful new painkilling drugs, Massachusetts Institute of Technology researchers recently reported online in the journal Psychopharmacology.
Blocking a common signaling messenger between cells might shut down the chronic pain and inflammation that plagues millions, says author Lisa A. Teather, postdoctoral associate in the MIT Department of Brain and Cognitive Sciences.
More than 100 million North Americans suffer from chronic pain, and around half of these people are partially or totally disabled by it. Inflammation may also be involved in the pathology of diseases such as Alzheimer’s.
Teather studies platelet-activating factor (PAF), identified as a blood-clotting agent in the 1970s. It was later found to cause the buildup of prostaglandins, derivatives of fatty acids found in most body tissues. Excess prostaglandins are associated with chronic pain and inflammation.
AN INSIDE STORY
PAF affects two kinds of receptors. Teather believes that receptors within cells regulate prostaglandin production. Drugs such as ibuprofen and aspirin relieve pain by blocking the formation of prostaglandins.
Teather and co-authors Richard J. Wurtman, C. H. Green Distinguished Professor in Brain and Cognitive Sciences and director of MIT’s Clinical Research Center; and Jane E. Magnusson of the Department of Clinical Neurosciences at the University of Calgary, found that drugs that interfere with PAF’s action block prostaglandin production and diminish pain and inflammation.
Although these drugs are not now used to treat inflammation or pain, one is in the herbal supplement gingko biloba. MIT has filed for patents on blocking PAF as a means for mediating inflammatory responses and alleviating pain.
In the study, rats that were given drugs known to block PAF action exhibited significantly less pain response than did rats that did not get the drugs.
Although the researchers do not yet have any data on PAF in humans, they believe that blocking PAF might be effective in the treatment of certain forms of acute and chronic pain.
CHECKING IMMUNE RESPONSE
"PAF controls many of the usual suspects in the inflammatory reaction," Teather said. Out-of-control inflammation is an indication of an immune response gone awry. At a molecular level, an overactive immune system leads to neurotoxicity, which may be a culprit in some neurological diseases.
A future painkiller that regulates PAF also could be useful in conjunction with morphine, which quickly loses its effectiveness in patients with chronic pain.
This study was supported in part by grants from the National Institutes of Mental Health and the Center for Brain Sciences and Metabolism Charitable Trust.
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