title: Individual Differences in Temporal Summation of Pain Reflect Pronociceptive and Antinociceptive Brain Structure and Function.
abstract: Temporal summation of pain (TSP), the perception of increasingly greater pain evoked by repetitive noxious stimuli, is highly variable between individuals. Individuals with facilitated pain processing and/or reduced pain-modulatory capabilities are regarded as pronociceptive, whereas individuals with reduced pain processing capacity are characterized as antinociceptive. Brodmann area (BA) 3a of the primary somatosensory cortex is part of an ascending pathway from the sensory thalamus that mediates TSP. Descending pain modulation involves projections from the subgenual anterior cingulate cortex (sgACC) to the periaqueductal gray to the rostral ventromedial medulla (RVM). Here, we tested the hypothesis that pronociceptive individuals have an enhanced TSP response compared with antinociceptive individuals, marked by facilitated ascending nociceptive processing and/or reduced capacity for descending pain modulation. Eighty healthy humans were tested with a TSP protocol and underwent structural and resting-state functional magnetic resonance imaging. We found large interindividual differences in TSP responses, which were positively correlated with functional connectivity (FC) between individuals' right sensory thalamus with their BA 3a (thal-BA 3a), and with cortical thickness in their insula and medial prefrontal cortex. In contrast, TSP was negatively correlated with FC between individuals' RVM with their sgACC (RVM-sgACC). When subjects were grouped as pronociceptive or antinociceptive based on whether they had greater thal-BA 3a or RVM-sgACC FC respectively, pronociceptive subjects showed greater TSP responses. Furthermore, TSP was positively correlated with the extent of imbalance toward ascending nociceptive processing. Our study indicates that individuals with enhanced TSP have facilitated ascending nociceptive processing and reduced pain-modulatory capacities.
  
  
  CONCLUSIONS
  This study provides novel evidence that an individual's propensity to experience amplified pain with repeated stimuli [i.e., temporal summation of pain (TSP)] reflects attributes of their "pain connectome," namely stronger ascending nociceptive and weaker descending pain-modulatory components. Understanding the individual neural mechanisms underlying TSP within individuals has implications for developing personalized pain-management strategies for chronic pain.
authors.affiliation: Division of Brain, Imaging & Behaviour Systems, Toronto Western Research Institute, Toronto M5T 2S8, Canada, Institute of Medical Science, University of Toronto, Toronto M5S 2J7, Canada, and.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Division of Brain, Imaging & Behaviour Systems, Toronto Western Research Institute, Toronto M5T 2S8, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Erpelding
authors.affiliation: Division of Brain, Imaging & Behaviour Systems, Toronto Western Research Institute, Toronto M5T 2S8, Canada, Institute of Medical Science, University of Toronto, Toronto M5S 2J7, Canada, and.
authors.forename: Aaron
authors.initials: A
authors.lastname: Kucyi
authors.affiliation: Division of Brain, Imaging & Behaviour Systems, Toronto Western Research Institute, Toronto M5T 2S8, Canada, Institute of Medical Science, University of Toronto, Toronto M5S 2J7, Canada, and.
authors.forename: Danielle D
authors.initials: DD
authors.lastname: DeSouza
authors.affiliation: Division of Brain, Imaging & Behaviour Systems, Toronto Western Research Institute, Toronto M5T 2S8, Canada, Institute of Medical Science, University of Toronto, Toronto M5S 2J7, Canada, and Department of Surgery, University of Toronto, Toronto M5T 1P5, Canada kdavis@uhnres.utoronto.ca.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Davis
mesh_terms: D000328:Adult; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D021621:Imaging, Three-Dimensional; D007206:Individuality; D008279:Magnetic Resonance Imaging; D008297:Male; D015233:Models, Statistical; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology*; D059225:Nociception / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D011601:Psychophysics; D013003:Somatosensory Cortex / Q000098:blood supply / Q000502:physiology*; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: RVM; S1; antinociception; functional connectivity; nociception; temporal summation of pain