Pain Relief Dare to Dream
If you suffer from chronic pain, or have patients who do, a recent study at the University of Toronto may provide you with new hope. Researchers at the University of Toronto, the Amgen Institute and the Hospital for Sick Children have discovered a genetic mechanism in pain modulation that may lead to a new approach to pain control. They identified the function of a gene called DREAM (downstream regulatory element antagonistic modulator), which appears to play a key role in how mice respond to heat, touch and inflammation. Genetically engineered mice lacking DREAM display reduced responses to models of acute thermal, mechanical and visceral pain, as well as models of inflammatory and chronic neuropathic pain. The latter is considered particularly exciting, as the medical community currently has no widely effective treatments for managing this debilitating type of pain.
DREAM was first identified in 1999, but was given three different names and three different suggested biological functions. It had previously been demonstrated to reduce production of dynorphin, an endorphin normally produced in response to pain or stress. Cheng et al. have now shown that DREAM is a transcriptional repressor, suppressing the genetic machinery that reads the DNA code for dynorphin. When the DREAM gene was absent, mice had increased production of prodynorphin mRNA and dynorphin A peptides in the spinal cord involved in transmitting and controlling pain messages. The attenuated pain response was evident for all types of pain and in all types of tissue.
Mice lacking the DREAM gene were otherwise completely normal and showed no major defects in motor function, learning or memory. There was no sign that the mice became addicted to the pain control chemicals that the body produced, which would provide an advantage over some currently available pharmacological therapies.
Estimates suggest that one in five people worldwide lives with chronic pain. Current pharmacologic approaches to pain management focus on opioids, anti-inflammatory medications, or analgesics such as acetaminophen. The recent findings suggest the possibility of a novel approach to pharmacological pain management, whereby drugs could block the ability of DREAM to bind to DNA, or could simply prevent the production of DREAM.
Of course, practical applications of this study are a long way off. Although it provides a major insight into pain mechanism in mice, it remains to be determined whether the same mechanism exists in humans.
Source
- Cheng HM, Pitcher GM, Laviolette SR et al. DREAM is a critical transcription repressor for pain modulation. Cell. 2002; 108:31-43.