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Where Is Pain in the Brain?

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Where Is Pain in the Brain?
Fort Lauderdale, Florida — Researchers are making progress in determining the neural mechanisms underlying modulation of cognitive acute pain.

A team at Stanford University in Palo Alto, California, has demonstrated the involvement of the dorsal anterior cingulate cortex (dACC), which could have important implications for future research targets.

Their work received a good deal of attention during the American Academy of Pain Medicine (AAPM) 29th Annual Meeting here.

"What is novel about this research direction is that we were looking for the area specifically involved in the cognitive modulation of pain within a clinical range," said team leader Heather Chapin, PhD, postdoctoral research fellow, anesthesia, Stanford University.

The involvement of the ACC in cognitive modulation of pain is not surprising. "This is a region that often shows up in relation to pain, cognitive control, and self-regulation," said Dr. Chapin. "In fact, our lab has used a different portion of the ACC as a target for real-time fMRI [functional MRI] neurofeedback in the past."

But what this new study found was that a different area of the ACC was associated with the perception of pain during pain modulation, she said.

Pain Modulation





Eric A. Dixon

The study included 15 healthy controls (mean age, 31.8 years; 8 women) that behavioral experiments had shown were able to cognitively modulate acute heat pain by at least 30%. The earlier behavioral experiment included 80 participants, and of those, about half were able to modulate their pain, said Eric A. Dixon, a research assistant in Dr. Chapin's lab who presented the findings at the AAPM meeting.

Researchers delivered a moderate heat pain stimulus to the left inside forearm of the participants. Participants were asked to use whatever cognitive strategies they wanted to increase and decrease pain (most used imagine/visualization strategies).

Meanwhile, the participants underwent fMRI. The scan consisted of an initial 30-second stimulation only (with no modulation) block followed by five 30-second "increase" and "decrease" modulation blocks in pseudorandom order. Each modulation block was followed by a 10-second rating period and a 40-second rest period.

In general, the analysis showed that pain modulation was associated with activation in areas related to body awareness and cognitive regulation and deactivation in areas related to sensation and emotion. Researchers found activation differences in areas related to pain processing, self-regulation, and cognitive control.

Midline frontal areas and rostral anterior cingulate showed greater deactivation during "increase" pain. Dorsal ACC and presupplementary motor area showed greater activation during "decrease" pain. Signal increases in the prefrontal cortex, dACC, and thalamus predicted decreased pain ratings.

These results show that successful cognitive modulation of pain involves brain areas associated with pain processing and cognitive control, said the authors.

Key Component

Importantly, the dACC, a region shown to be important for self-regulation, was correlated with pain ratings and showed a significant difference in activation between conditions. This, said the researchers, indicates that the dACC may be a key component in modifying pain perception within a clinically significant range.

The researchers now plan to take this a step further and study the dACC in neuromodulation. They will use real-time fMRI to train participants to modify their pain experience by directly controlling neural processes related to pain.

Asked for his opinion on this research, Eric Kerstman, MD, assistant professor, physical medicine and rehabilitation with a subspecialty in pain medicine, Baylor College of Medicine, Houston, Texas, said that although he's not a researcher in this field, it sounds like a good example of basic science that could be translated to clinical medicine.

"This is translational science; it potentially could be translated into clinical application to maybe develop new medications that act on certain parts of the brain that modulate pain," he said. "The idea from this is that you might be able to target that area in order to control pain more effectively."

The study was supported by a grant from the National Institutes of Health, the National Institute on Drug Abuse, and the Redlich Pain Research Endowment.

American Academy of Pain Medicine (AAPM) 29th Annual Meeting. Poster 227. Presented April 12, 2013.

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