DREAMing away pain. (Biomedicine).The mutant mice didn't make sense. Josef M. Penninger of the University of Toronto Research at the University of Toronto has been responsible for the world's first electronic heart pacemaker, artificial larynx, single-lung transplant, nerve transplant, artificial pancreas, chemical laser, G-suit, the first practical electron microscope, the first cloning of T-cells, and his colleagues had disabled a rodent gene that they thought controlled another gene, one involved in the immune system. Yet the mice had no immune defects or any other obvious problems. "The more we went into the project the more confused we got," recalls Penninger. When the mice were subjected to an array of behavioral tests, however, the scientists noticed that the rodents weren't as sensitive to acute and chronic forms of pain, including pain caused by heat, toxic substances, and nerve damage. The gene that Penninger's team had mutated encodes a protein called DREAM (downstream regulatory element antagonistic modulator), which is a so-called transcription factor. As such, it binds to DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. and regulates the activity of genes. Instead of controlling an immunity-related gene, as Penninger's team expected, DREAM appears to suppress the production of a natural opioid called dynorphin. The mice lacking DREAM overproduce o·ver·pro·duce tr.v. o·ver·pro·duced, o·ver·pro·duc·ing, o·ver·pro·duc·es To produce in excess of need or demand. o this opioid in spinal cord nerve cells, where it affects pain perception, Penninger's group reports in the Jan. 11 Cell. These results add to a growing puzzle. In contrast to the new work, some experiments have shown that dynorphin actually promotes pain. The new work "is sort of counterintuitive coun·ter·in·tu·i·tive adj. Contrary to what intuition or common sense would indicate: "Scientists made clear what may at first seem counterintuitive, that the capacity to be pleasant toward a fellow creature is ... ," says Robert M. Caudle cau·dle n. A warm drink consisting of wine or ale mixed with sugar, eggs, bread, and various spices, sometimes given to ill persons. [Middle English caudel of the University of Florida University of Florida is the third-largest university in the United States, with 50,912 students (as of Fall 2006) and has the eighth-largest budget (nearly $1.9 billion per year). UF is home to 16 colleges and more than 150 research centers and institutes. . "Dynorphin is probably more complicated than we realized" Penninger suggests that dynorphin has either a pain-killing or pain-enhancing action depending on which cell-surface protein it binds. Although drags that target transcription factors are rare, the team is developing inhibitors of DREAM to test if they are a new class of pain relievers. DREAM is "an intriguing target" he says. --J.T. |
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