DURHAM, N.C.--Duke University Medical Center scientists have discovered a biological mechanism in mice that prolongs morphine's painkilling effects. Their findings could lead to the development of new drugs that make morphine last longer and relieve pain at lower doses.
The researchers report in the Dec. 24 Science that morphine prevents pain longer and more completely when administered to mice engineered to lack a protein switch called "beta-arrestin 2." Beta-arrestin normally comes into play after morphine is administered by blocking the chemical signal that morphine sends to the brain to suppress pain sensation. Thus, when the researchers genetically altered mice to lack beta-arrestin, morphine remained effective for longer periods in those mice, and lower morphine doses were required to achieve pain relief in these mice.
The findings come from the laboratories of Dr. Robert Lefkowitz and Marc Caron, both Howard Hughes Medical Institute investigators at Duke Medical Center.
At the heart of the study is a metabolic process known as "desensitization," in which an initially receptive cell develops a reduced response to a chemical stimulus. For example, desensitization occurs when a person who has entered a coffee shop quickly becomes accustomed to the aroma and no longer notices it. The stimulus hasn't disappeared, but the olfactory sensory cells that first responded to the smells ignore the stimulus after a time.
Beta-arrestin is part of the cell's machinery that produces desensitization to morphine after the morphine molecule initially binds to a receptor on the surface of nerve cells. Receptors are proteins that relay chemical signals from outside the cell to the cell's machinery to cause a cellular response.
"When the morphine receptor is activated by binding morphine, it transmits a message that
initially suppresses pain perception," explained Laura Bohn, a postdoctoral fellow in Caron's
Contact: Renee Twombly
Duke University Medical Center