Abstract

How pain emerges from cortical activities remains an unresolved question in pain neuroscience. A first step toward addressing this question consists in identifying brain activities that occur preferentially in response to painful stimuli in comparison to non-painful stimuli. A key confound that has affected this important comparison in many previous studies is the intensity of the stimuli generating painful and non-painful sensations. Here, we compared the brain activity during iso-intense painful and tactile sensations sampled by functional MRI in 51 healthy participants. Specifically, the perceived intensity was recorded for every stimulus and only the stimuli with rigorously matched perceived intensity were selected and compared between painful and tactile conditions. We found that all brain areas activated by painful stimuli were also activated by tactile stimuli, and vice versa. Neural responses in these areas were correlated with the perceived stimulus intensity, regardless of stimulus modality. More importantly, among these activated areas, we further identified a number of brain regions showing stronger responses to painful stimuli than to tactile stimuli when perceived intensity was carefully matched, including the bilateral opercular cortex, the left supplementary motor area and the right frontal middle and inferior areas. Among these areas, the right frontal middle area still responded more strongly to painful stimuli even when painful stimuli were perceived less intense than tactile stimuli, whereas in this condition other regions showed stronger responses to tactile stimuli. In contrast, the left postcentral gyrus, the visual cortex, the right parietal inferior gyrus, the left parietal superior gyrus and the right cerebellum had stronger responses to tactile stimuli than to painful stimuli when perceived intensity was matched. When tactile stimuli were perceived less intense than painful stimuli, the left postcentral gyrus and the right parietal inferior gyrus still responded more strongly to tactile stimuli while other regions now showed similar responses to painful and tactile stimuli. These results suggest that different brain areas may be engaged differentially when processing painful and tactile information, although their neural activities are not exclusively dedicated to encoding information of only one modality but are strongly determined by perceived stimulus intensity regardless of stimulus modality.

Highlights

  • IntroductionTransient nociceptive stimuli causing pain elicit robust responses in a set of widely distributed brain regions including the thalamus, the primary and secondary somatosensory areas, the insula, the cingulate cortex and some areas in the frontal and parietal lobes (Boly et al, 2008; Garcia-Larrea and Peyron, 2013; Iannetti et al, 2005b; Ingvar, 1999; Jones, 1998; Ploghaus et al, 1999; Stern et al, 2006; Talbot et al, 1991; Tracey and Mantyh, 2007; Wager et al, 2013; Whyte, 2008)

  • To rigorously match the perceived intensity between painful and tactile stimuli, a subset of stimuli was selected in each participant

  • Using a voxel-wise general linear model (GLM) analysis modelling the perceived stimulus intensity regardless of stimulus modality, we found that the amplitude of functional magnetic resonance imaging (fMRI) responses correlated with perceived stimulus intensity in a broad network of brain areas

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Summary

Introduction

Transient nociceptive stimuli causing pain elicit robust responses in a set of widely distributed brain regions including the thalamus, the primary and secondary somatosensory areas, the insula, the cingulate cortex and some areas in the frontal and parietal lobes (Boly et al, 2008; Garcia-Larrea and Peyron, 2013; Iannetti et al, 2005b; Ingvar, 1999; Jones, 1998; Ploghaus et al, 1999; Stern et al, 2006; Talbot et al, 1991; Tracey and Mantyh, 2007; Wager et al, 2013; Whyte, 2008). Many studies have attempted to identify the neural correlates of pain using a variety of brain imaging techniques and suggested neural activities that might be preferentially involved in pain processing It has been claimed, on the basis of recordings using intracerebral local field potentials (LEPs), scalp electroencephalography (EEG), functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that the secondary somatosensory cortex (S2) (Peyron et al, 2002), the insula (both posterior (Isnard et al, 2011; Peyron et al, 2002) and anterior (Peyron et al, 2002)) and the anterior cingulate cortex (ACC) (Lieberman and Eisenberger, 2015) might contain neural activities selective to pain. Given that the amplitude of neural activity in many brain areas was found to correlate with stimulus intensity (Coghill et al, 1999; Iannetti et al, 2008), it remains unclear whether these previously identified brain areas responded to pain preferentially or because painful stimuli were more intense (Hu and Iannetti, 2016)

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