"This protein appears to be the master switch for controlling pain," said Dr. R. Adron Harris, director of the university’s Waggoner Center for Alcohol and Addiction Research and a professor at the College of Natural Sciences and College of Pharmacy, who led the research.
The findings will be published online by the Proceedings of the National Academy of Sciences the week of Dec. 16. They mirror those of an accompanying paper in the same issue by investigators at the University of California, San Francisco.
Both research groups analyzed the pain response of mice that had been genetically modified to lack the gene that produces the GIRK2 protein. The work was based on initial observations by Japanese researchers that these mice fail to experience pain relief after receiving alcohol. But a larger role for the protein was unexpected because pain-relieving drugs (analgesics) vary greatly in their composition.
The GIRK2 protein exists on the surface of nerve cells, where analgesics are able to interact with proteins linked to GIRK2. This interaction activates GIRK2 to function as a portal for potassium ions to enter the cell. Once the ions enter a nerve cell, the sensitivity to pain decreases.
To study the protein’s role, Harris and research scientist Yuri Blednov injected normal mice and those lacking GIRK2 with one of a number of analgesic drugs. They included alcohol, clonidine and a cannabinoid, which is the active component in marijuana. After a drug had time to take effect, the researchers placed the mouse on a hot plate that was warm enough to cause it to lift or flick its paw in response to the heat.
Harris noted that each animal was placed on the hot plate for a minute at most, and said, "When they felt the heat, they moved a paw, and we removed them."
For all but one drug, mice lacking GIRK2 responded more rapidly to heat than their normal counterparts who had received the same analgesic. This indicated that the drugs did not make it easier for the animals to tolerate pain, as would be expected if GIRK2 is needed for the drugs to work.
When mice were made to swim in water for five minutes before being placed on a hot plate, the normal animals reacted slower to pain. Previous studies had indicated that this occurs because exercise causes the brain to release endorphins and other chemicals, as-yet-to-be identified, that dull the pain response. The innate pain relief system failed to work as well, though, in mice that Harris studied that lacked GIRK2.
In addition, the general response of male and female mice lacking GIRK2 differed. Females responded slower to pain, suggesting that they still received some benefit from analgesics due to other, unidentified pain-relieving pathways in their bodies.
Harris noted that this echoes what is known about the more complex pain response that exists in women, who are more sensitive to pain and respond better to analgesics than men.
For more information contact: Barbra Rodriguez, media relations, College of Natural Sciences, 512-232-0675.
