Researchers at the University of Toronto, The Hospital for Sick Children and the Amgen Institute have discovered a genetic mechanism involved in pain modulation that could lead to an entirely new approach to pain control. The results of their research are published in the Jan. 11 issue of the journal Cell.
In the study, genetically engineered mice lacking a gene called DREAM (downstream regulatory element antagonistic modulator) showed a dramatic loss of pain sensitivity compared to mice who had the DREAM gene.
"This is an exciting development," says study co-author Professor Michael Salter, director of the University of Toronto Centre for the Study of Pain and a senior scientist at The Hospital for Sick Children. "There's a great interest in this finding because it's so different from the traditional approaches researchers have been taking to pain management."
The work was done in the laboratory of principal investigator Professor Josef Penninger at Amgen by graduate students Mary Cheng and Graham Pitcher, lead authors of the study.
The DREAM gene's role in reducing production of the chemical dynorphin had been previously identified.
DREAM produces a protein that suppresses the genetic machinery that reads the DNA code for dynorphin, which decreases dynorphin production. Dynorphin is a peptide normally produced in the body. Known as an endorphin, it is produced in response to pain or stress. "We knew about DREAM and its role in dynorphin expression, but the purpose of this study was to determine DREAM's actual physiological function," says Salter.
When the DREAM gene was absent in mice, the researchers discovered increased production of dynorphin in the region of the spinal cord involved in transmitting and controlling pain messages.
The mice, they discovered, had decreased sensitivity to acute, inflammatory and neuropathic pain. "The attenuated pain response was evident for all types of pain in all types o
Contact: Megan Easton
University of Toronto