Intelligence comes at a painful price--at least it does for one strain of genetically engineered mice. In the February issue of Nature Neuroscience, researchers show that transgenic mice previously shown to score high on mouse intelligence tests are more sensitive to chronic pain. The finding bolsters a link between the physiological mechanisms of pain and memory and could point the way to better drugs for chronic pain.
A year and a half ago, the engineered mice caused a media stir, when their creators at Princeton University reported in Nature that they outperformed their normal counterparts on a variety of learning and memory tests (ScienceNOW, 1 September 1999 ). The researchers had meddled with the animals' so-called NMDA receptors, which play a variety of roles in the central nervous system; the "smart" mice make an abundance of a particular type of NMDA receptor which contains the so-called NR2B subunit. To find out if these receptors are also involved in pain responses, Min Zhuo and his colleagues at Washington University in St. Louis subjected the engineered mice to a battery of tests.
When the researchers injected one hind paw of the mice with a compound that causes chronic, painful swelling, the NR2B mice continued to lick the affected paw longer and were more likely to withdraw it in response to a light touch. In contrast, there was no difference between NR2B mice and normal mice in their response to acutely painful stimuli, such as a heating probe applied to the tail. Zhuo says the findings suggest that future drugs able to selectively target NR2B-containing NMDA receptors could relieve chronic pain without disrupting a patient's responses to acutely painful stimuli that warn of immediate danger--a hot stove, for example.
That's a nice idea, says Edwin McCleskey, a neurobiologist at Oregon Health Sciences University in Portland, Oregon, but he warns that results in genetically altered mice don't always apply to humans. It does make sense, however, that a single receptor would play a role in both pain perception and memory, says David Hewitt, a clinical pain researcher at Emory University in Atlanta. "In evolutionary terms, the most important thing to know is not to hurt yourself--pain is one of the most important things to remember."