Blocking Potent Oxidant Could Prevent Morphine Tolerance
FRIDAY Nov. 2, 2007 -- Blocking a substance called peroxynitrite, a potent oxidant that's formed when patients take morphine, can prevent the development of tolerance to the pain-relieving effects of the narcotic, according to animal tests conducted by Saint Louis University of Medicine researchers.
They said their findings, published in the November issue of the Journal of Clinical Investigation, could lead to new therapies that prevent morphine tolerance and the severe side effects caused by having to give patients escalating doses of the painkiller.
Morphine and other opiate narcotics are the most powerful treatments for acute and chronic pain. However, their pain-killing effectiveness decreases quickly and significantly with repeated doses.
In this study, researchers found that repeated doses of morphine caused peroxynitrite to develop in the spinal cord, resulting in inflammation and damage to proteins and DNA in that area. Putting the brakes on peroxynitrite -- either by causing it to decompose once it formed or by blocking it from forming in the first place -- prevented morphine tolerance.
"We believe these findings represent a major breakthrough in understanding how tolerance to the pain-relieving action of morphine and other opiate medications develops -- and how it can be prevented from happening in the first place," study author Daniela Salvemini, a professor of internal medicine in the division of pulmonary, critical care and sleep medicine, said in a prepared statement.
This research may help in the development of therapies that enable patients to take morphine without developing tolerance.
"For instance, when morphine is administered, another drug could be given simultaneously that prevents peroxynitrite from working and thus causing tolerance to develop," Salvemini explained.
Posted: November 2007