Researchers discover pain gene
TORONTO, Jan 10, 2002 (United Press International via COMTEX) -- Researchers
have discovered a gene that controls pain transmission in the spinal chord that
they say could herald a new approach to pain management.
The research is published in the Jan. 11 issue of the journal Cell.
Investigators studying genetically engineered mice lacking the DREAM --
downstream regulatory element antagonistic modulator -- gene found they had less
sensitivity to pain compared to mice with the DREAM gene.
"This gives us a new way to think about pain and pain management" co-author
Dr.Michael Salter, director of the University of Toronto Center for the Study of
Pain, told United Press International.
"It's so different from the traditional approaches to pain management and,
clinically, it offers the hope getting away from the side effects of currently
used drugs, including altered cognition, addiction and gastrointestinal
problems," he said.
DREAM makes a protein that suppresses production of dynorphin, a naturally
produced "feel good" chemical or endorphin. Dynorphin is produced in response to
pain or stress.
In the absence of the gene, the researchers found more production of dynorphin
-- and therefore less pain -- in the region of the spinal cord where pain
messages are transmitted and controlled.
"We knew about DREAM and its role in dynorphin expression, but the purpose of
this study was to determine DREAM's actual physiological function," Salter said.
The altered mice showed less sensitivity to all types of pain.
"The attenuated pain response was evident for all types of pain in all types of
tissue tested," Salter said. "The fact that even mice with neuropathic pain --
the kind of sharp, chronic pain resulting from nerve injury -- experienced this
effect is exciting, because the medical community currently doesn't have any
widely effective treatments for this debilitating type of pain."
"What this reveals is that there is a gating mechanism in the spinal chord which
operates by molecular switches," Dr. Clifford Woolf, professor of medicine at
Harvard Medical School in Cambridge, Mass., told UPI. "Some switches act to open
pain transmission and others to close pain transmission. DREAM appears to be one
of these switches which acts to enable pain transmission. So removing it blocks
pain transmission."
Typically, doctors use morphine and other opioids to stimulate cell receptors
for endorphins -- or aspirin and aspirin-like drugs to block the pain related
Cox enzymes. The DREAM gene binds directly to DNA and controls the production of
a protein in the body's own and natural opioid system.
"These findings point to a novel pharmacological approach to pain management
where researchers will be looking for drugs that could block the ability of
DREAM to bind to DNA or simply prevent the production of DREAM," Salter said.
The genetically altered mice showed no changes in any other normal functions.
Also, they did not become addicted to the pain control chemicals that their
bodies produced.
"Pain is a huge, silent public health crisis that is only beginning to be
addressed by researchers," Salter said. "This declaration highlights a growing
awareness of the vast problem of untreated or under-treated pain, and we hope
this research will contribute in a significant way to current efforts by
scientists to confront this challenge."
The study was funded by the National Cancer Institute of Canada, the Canadian
Institutes of Health Research and Amgen Inc.
--
(Reported by Bruce Sylvester from West Palm Beach, Fla.)
Copyright 2002 by United Press International.
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