Identifying pain-specific connectivity in the human brain

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We have all experienced pain. It signals potential injury, and comprises sensory, emotional, motivational and cognitive dimensions, which must be integrated to mount an appropriate response. Brain imaging studies using functional magnetic resonance imaging (fMRI) have repeatedly shown that subjecting individuals to painful stimuli results in a consistent pattern of brain activity. However, this pattern is not pain specific — in fact, this pattern is indistinguishable from a touch stimulus. This is because the observed pattern represents the extent to which pain captures our attention — i.e., pain's salience. As such, there has yet to be a pain-specific brain region, or set of brain regions. Although the activation pattern is indistinguishable between pain and touch, these stimuli feel very different, and thus must have different representations in the brain.******Brain regions do not function in isolation. They form networks to integrate information and produce perceptual experiences and behaviour. Therefore, although the same sets of brain regions are activated by touch and pain, these regions may be forming networks with different regions. Determining if this is the case could reveal a fundamental mechanism by which pain is perceived in the brain. ******The overall aim of this proposal is to identify a mechanism for pain perception. To achieve this, we will identify network differences during painful and touch stimuli, that have been matched for salience. However, given that pain and touch are perceptually different — pain is inherently unpleasant, whereas touch is not — it is important to determine whether brain differences between touch and pain are related to unpleasantness, rather than pain itself. One way to answer this question is to compare brain activity elicited by unpleasant stimuli from different modalities. Therefore, the second aim of this study is to compare whether the identified pain connectivity 1 encodes unpleasant stimuli across three different modalities: visual, tactile and nociceptive. Third, the strength of pain-specific connectivity may be related to the intensity of the pain perceived. The third aim of this study is to test whether the pain specific connectivity shows a graded response to different stimulus intensities. Finally, we will determine whether there is a structural basis for the observed pain-specific connectivity using novel structural brain imaging techniques. These studies will greatly advance our fundamental understanding of the pain system, and have profound translational impact for health researchers to develop a biomarker for pain, and identify novel therapeutic markers.