Dream away pain

Pain-free mice in a dream. Credit: J.Penniger.

A protein called DREAM has been discovered to have a critical role in pain perception, in mice at least, affecting how they feel heat, touch and inflammation.

Mice without the DREAM protein do not feel pain, according to Michael Salter, director of the University of Toronto Centre for the Study of Pain and a senior scientist at The Hospital for Sick Children, and his colleagues there and at the Amgen Institute. The findings could help in developing ways to eradicate the often-debilitating pain of arthritis, cancer, and other diseases. Conventional painkillers often fail these patients.

The Downstream Regulatory Element Antagonistic Modulator (DREAM) was discovered in 1999. It was found that a lack of the gene for this protein is associated with high concentrations of the endorphin peptide dynorphin in the spinal cord, which acts a natural painkiller. "This is an exciting development," says Salter, "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 Josef Penninger at Amgen by graduate students Mary Cheng and Graham Pitcher.

DREAM suppresses the genetic machinery that reads the DNA code for dynorphin, reducing production. Dynorphin is produced in response to pain or stress. Mice without the DREAM gene made more dynorphin in the region of the spinal cord involved in transmitting and controlling pain messages. The mice, the team discovered, had decreased sensitivity to acute, inflammatory and neuropathic pain.

The research suggests that one day it might be possible to modulate pain without standard analgesics, such as opiates and aspirin. Current approaches to pain management focus on drugs such as morphine that stimulate cell receptors for the endorphin family of proteins or drugs such as aspirin that block the inflammatory response. DREAM works differently by binding directly to DNA and regulating the expression of an endorphin. "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," says Salter.

However, as with any preliminary discovery it will be many years before a product is developed for patients' use.

Cell, 108, 31-43, (2002)^*

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