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researchers switched to using higher-resolution video cameras, their predictions became up to 97% The author file accurate. The study would have been much quicker had researchers begun the project using a $600 cam- Jeffrey Mogil era versus a $300 camera, says Mogil. “I’m kicking Putting a face on in mice should improve myself for being so cheap.” our ability to measure it. Mogil also wanted to know whether mouse facial expression could be used to study the emotional In the late 1980s, Jeffrey Mogil intended to become a aspects of pain, which clinicians are eager to under- pharmacologist. He entered John Liebeskind’s labora- stand and mitigate. If facial expression conveyed tory at the University of California, Los Angeles, where pain-related emotion, Mogil reasoned, then lesions researchers had access to strains of mice that exhibited to appropriate brain areas should prevent grimaces varying pain thresholds. after painful stimuli. Mogil’s team created lesions in Soon after Mogil joined the two regions associated with pain emotion in humans. lab, his advisor came across This damage had no effect on grimacing. Next, Mogil a paper explaining how to came across evidence for a third brain area. Lesions identify specific genes via in this area resulted in only a very modest effect. But selective breeding. Mogil just after viewing these disappointing data, Mogil was the newest graduate received an e-mail explaining that two of the mice student; he expressed an had lesions in the wrong brain region. “Suddenly interest and suddenly found this experiment that had failed actually had worked himself getting into pain beautifully.” genetics, becoming perhaps Training people to use the MGS is straightforward, the first scientist to study says Mogil. Even a novice can be trained to 75% this systematically. accuracy within an hour. However, the process of “For a long time no one cared,” Mogil recalls. “Pain rendering video into still researchers had never heard of genetics.” He used to images that can be used “This is directly go to the Society for Neuroscience meetings and stand for assessment is time- alone by his posters. Then transgenic knockout mice consuming. Whereas get- taken from a started becoming ubiquitous tools for disease model- ting results from a stan- human scale.” ing, and researchers realized that understanding the dard behavioral test may genetic background of a new mouse strain was cru- take only minutes, getting —Jeffrey Mogil cial for interpreting data. Suddenly everyone needed images appropriate for Mogil’s data and insights. “Voila,” he says, “career.” MGS can take hours or even days per experiment. Later, as a professor at McGill University, Mogil Clinicians seem particularly keen to see results showed, surprisingly, that mice have a heightened using the MGS. “The clinical people love anything

© 2010 Nature America, Inc. All rights reserved. All rights Inc. America, Nature © 2010 response to painful stimuli after observing a cage- that reminds them of humans, and this is directly mate in pain. His team established that the way mice taken from a human scale,” says Mogil. Basic scien- conveyed pain to each other was visual, but exactly tists, however, seem less receptive, perhaps because how the communication occurred was unclear. “To they have already established tests for studying pain see how mice could observe each other’s pain, we and do not want to be reminded that these might had to see if we could observe their pain,” Mogil measure behavioral responses that only indirectly says. “Then we realized that that’s a more impor- assess desired clinical outcomes. tant question.” Addressing that question resulted in Currently Mogil is repeating classic experiments a new way to measure pain, the mouse grimace scale in the pain field to assess whether the MGS predicts (MGS; p. 447). efficacy in humans better than other measures and It was not hard to show that mice convey pain is collaborating with software engineers to develop through their facial expressions, says Mogil. Faced algorithms that can automatically identify appropri- with a collage of faces of mice in painful and pain- ate frames. He believes that face-based assessment free situations, even a casual human observer can can be sped up, but he is also hopeful that researchers distinguish which set of mice is in pain, says Mogil, may be willing to use more labor-intensive tests if but being able to assess pain from a single photo- data from such studies are more relevant to relieving graph was considerably more difficult. human pain. Mogil and colleagues broke mouse facial expres- Monya Baker sion into parameters that could be scored by obser- vations of eyes, nose, ears, cheeks and whiskers. Langford, D.J. et al. Coding of facial expressions Researchers using these parameters could pre- of pain in the laboratory mouse. Nat. Methods 7, dict whether images depicted mice subjected to 447–449 (2010). pain stimuli with 72% accuracy. However, when

nature methods | VOL.7 NO.6 | JUNE 2010 | 415