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Research Letter |

The “Pain Matrix” in Pain-Free Individuals

Tim V. Salomons, PhD1; Gian Domenico Iannetti, MD, PhD2; Meng Liang, PhD3; John N. Wood, PhD4
[+] Author Affiliations
1School of Psychology and Clinical Language Sciences, University of Reading, Reading, England
2Neuroscience Pharmacology and Physiology, University College London, London, England
3School of Medical Imaging, Tianjin Medical University, Tianjin, China
4Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London, England
JAMA Neurol. 2016;73(6):755-756. doi:10.1001/jamaneurol.2016.0653.
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This study administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with functional magnetic resonance imaging.

Human functional imaging provides a correlative picture of brain activity during pain. A particular set of central nervous system structures (eg, the anterior cingulate cortex, thalamus, and insula) consistently respond to transient nociceptive stimuli causing pain. Activation of this so-called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals,1,2 and is now considered a candidate biomarker for pain in medicolegal settings and a tool for drug discovery. The pain-specific interpretation of such functional magnetic resonance imaging (fMRI) responses, although logically flawed,3,4 remains pervasive. For example, a 2015 review states that “the most likely interpretation of activity in the pain matrix seems to be pain.”4 Demonstrating the nonspecificity of the pain matrix requires ruling out the presence of pain when highly salient sensory stimuli are presented. In this study, we administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with fMRI. Loss-of-function SCN9A mutations in these individuals abolishes sensory neuron sodium channel Nav1.7 activity, resulting in pain insensitivity through an impaired peripheral drive that leaves tactile percepts fully intact.5 This allows complete experimental disambiguation of sensory responses and painful sensations.

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Pain Matrix Activation in Pain-Free People

A, Neurosynth-based pain matrix (red) and the regions where all control participants had significant activation in response to noxious stimulation (blue). B, Activation levels (z scores) of single participants within regions of the pain matrix. C, Neurosynth-based pain matrix (red) and pain matrix regions where pain-free individuals had significant activation (yellow). D, Conjunction (green) of pain-free and control activations within the Neurosynth-based pain matrix regions.

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