title: An fMRI-based neurologic signature of physical pain.
abstract: BACKGROUND
  Persistent pain is measured by means of self-report, the sole reliance on which hampers diagnosis and treatment. Functional magnetic resonance imaging (fMRI) holds promise for identifying objective measures of pain, but brain measures that are sensitive and specific to physical pain have not yet been identified.
  
  
  METHODS
  In four studies involving a total of 114 participants, we developed an fMRI-based measure that predicts pain intensity at the level of the individual person. In study 1, we used machine-learning analyses to identify a pattern of fMRI activity across brain regions--a neurologic signature--that was associated with heat-induced pain. The pattern included the thalamus, the posterior and anterior insulae, the secondary somatosensory cortex, the anterior cingulate cortex, the periaqueductal gray matter, and other regions. In study 2, we tested the sensitivity and specificity of the signature to pain versus warmth in a new sample. In study 3, we assessed specificity relative to social pain, which activates many of the same brain regions as physical pain. In study 4, we assessed the responsiveness of the measure to the analgesic agent remifentanil.
  
  
  RESULTS
  In study 1, the neurologic signature showed sensitivity and specificity of 94% or more (95% confidence interval [CI], 89 to 98) in discriminating painful heat from nonpainful warmth, pain anticipation, and pain recall. In study 2, the signature discriminated between painful heat and nonpainful warmth with 93% sensitivity and specificity (95% CI, 84 to 100). In study 3, it discriminated between physical pain and social pain with 85% sensitivity (95% CI, 76 to 94) and 73% specificity (95% CI, 61 to 84) and with 95% sensitivity and specificity in a forced-choice test of which of two conditions was more painful. In study 4, the strength of the signature response was substantially reduced when remifentanil was administered.
  
  
  CONCLUSIONS
  It is possible to use fMRI to assess pain elicited by noxious heat in healthy persons. Future studies are needed to assess whether the signature predicts clinical pain. (Funded by the National Institute on Drug Abuse and others.).
authors.affiliation: Department of Psychology and Neuroscience, University of Colorado, Boulder, 80305, USA. tor.wager@colorado.edu
authors.forename: Tor D
authors.initials: TD
authors.lastname: Wager
authors.forename: Lauren Y
authors.initials: LY
authors.lastname: Atlas
authors.forename: Martin A
authors.initials: MA
authors.lastname: Lindquist
authors.forename: Mathieu
authors.initials: M
authors.lastname: Roy
authors.forename: Choong-Wan
authors.initials: CW
authors.lastname: Woo
authors.forename: Ethan
authors.initials: E
authors.lastname: Kross
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use; D001185:Artificial Intelligence; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010146:Pain / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology; D010147:Pain Measurement / Q000379:methods*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D012372:ROC Curve; D000077208:Remifentanil; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil