Research - Opiates

Prolonging Painkillers
By Mary Beckman

Morphine and other opiates dull pain, but they don't stick around for long. Almost immediately, a class of enzymes known as peptidases burst onto the scene and degrade these painkillers. Now researchers have identified a naturally occurring molecule in humans that blocks this process, prolonging the effect of opiates. The findings, say the researchers, may lead to new ways to combat pain.

Three years ago, researchers got their first hint that animals could block opiate-destroying enzymes. When neuroendocrinologists stressed rats, they found a small protein or peptide called sialorphin inhibited the action of neutral endopeptidase (NEP), which breaks down a natural opiate known as enkephalin. Do humans make a similar peptide?

Neuroendocrinologist Catherine Rougeot of the Institut Pasteur in Paris suspected so. Previous work hinted that people secrete a mystery molecule in their mouths that could inhibit NEP, so Rougeot and colleagues started isolating peptides from saliva. The team identified a peptide that was five amino acids long and could block NEP in a test tube. Calling it opiorphin, the team modified it slightly to make it easier to work with in rats, naming the new peptide YQRFSR. Then the researchers injected YQRFSR into the bloodstreams of rats and, 15 minutes later, injected a compound that stimulates painful inflammation into the rats' hind paws. Rodents without YQRFSR licked their paws in discomfort for more than 2 minutes, but rats that got the small molecule only tended their paws for a little over a minute and a half, indicating less pain.

© 2006 American Association for the Advancement of Science