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Babies cry. They cry when they’re hungry, when they’re tired, when they need a diaper change — and when they’re in pain. For doctors, this is a problem. Could a baby’s cry mean an anesthetic isn’t working well during a procedure? That a painkiller for postoperative pain has worn off? Or could it mean something else entirely?

Scientists at the University of Oxford think they have found a new way around that problem. Neuroscientist Caroline Hartley and her colleagues studied 72 infants undergoing medically necessary painful procedures, like a needle prick for a blood test. They found, using electrodes on the babies’ scalps, a signature change in brain activity about a half-second after a painful stimulus. In the future, that measure could help pain researchers objectively establish if an infant is in pain and, ultimately, determine how to manage it. The study was published in Science Translational Medicine on Wednesday.


Other indicators are currently used to gauge an infant’s pain, like heart rate, oxygen saturation levels, and facial expression. Doctors should still use these indicators when they examine individual patients, Hartley noted, because they’re easy to assess in a clinical setting. But an EEG signature could be more specific than those and less likely to be triggered by other stressful, non-painful events.

And the approach is about to get its first field test. Hartley and another one of her coauthors have started recruiting patients for what is expected to be a three-year clinical trial to test the efficacy of morphine in infants. Treating an infant in pain is not like treating a tiny adult: Infants’ skins and intestines absorb drugs differently, and they can have different levels of enzymes that break down drugs and the receptors to which drugs bind, too.

This new EEG assessment will be one of two ways Hartley and her colleagues measure pain in their trial, in addition to a test based on an infant’s behavior, the revised Premature Infant Pain Profile.


That test was revised in 2014 by Bonnie Stevens, a professor at the University of Toronto and a senior scientists at the Hospital for Sick Children. Stevens, who was not involved in the EEG research, said the research was “exciting.”

“I think it’s really moving the science of pain assessment in babies forward,” Stevens said. However, she added, “I don’t think looking at EEG responses is going to replace everything else.”

Stevens agreed with the authors of the paper that an EEG is a specialized measurement best suited for research. (Determining medication dosages for infants is an area that needs more research — not just for pain medication, but for many other kinds.) She also noted that the researchers validated their results with only a part of the revised PIPP test and could have observed the EEG signals for a longer window to match the time it takes to see a behavioral response.

Hartley acknowledged the study had other limitations, too. The study included 12 babies who were born after 34 weeks but before a full 40-week gestational period — but babies born even earlier than 34 weeks have different brain activity patterns, so the test wouldn’t be usable for them. The accuracy of the test is not great on an individual level; it could only accurately detect an infant in pain 64 percent of the time and was able to identify an infant not in pain 65 percent of the time.

“We think that further research is needed before you could use it [on an individual basis],” Hartley said. However, it does a better job of determining across a group of infants if a painkiller is working as it should. In one of the team’s experiments, 11 out of 12 infants had a decreased pain-related EEG signal after doctors applied a topical anesthetic to their feet.

Ultimately, an EEG could be a new, potentially valuable tool for pain researchers, Stevens said.

“At the end of the day, we are going to need a multi-modal pain assessment for babies that is going to include both behavioral and physiological [measures] as well as something like EEG, which will pull everything together to give us a comprehensive pain assessment in babies.”