title: Pupil responses and pain ratings to heat stimuli: Reliability and effects of expectations and a conditioning pain stimulus.
abstract: The locus coeruleus (LC) signals salience to sensory stimuli and these responses can modulate the experience of pain stimuli. The pupil dilation response (PDR) to noxious stimuli is thought to be a surrogate for LC responses, but PDR response to Peltier-controlled noxious heat stimuli, the most commonly used method in experimental pain research, has not been described.
  
  
  
  Healthy volunteers were presented with randomly presented heat stimuli of 5 sec duration and provided pain intensity ratings to each stimulus. Pupillometry was performed and a method developed to quantify the PDR relevant to these stimuli. The stimulus response, reliability, and effect of commonly used manipulations on pain experience were explored.
  
  
  
  A method of artifact removal and adjusting for lag from stimulus initiation to PDR response was developed, resulting in a close correlation between pain intensity rating and PDR across a large range of heat stimuli. A reliable assessment of PDR within an individual was achieved with fewer presentations as heat stimulus intensity increased. The correlation between pain rating and PDR was disrupted when cognitive load is increased by manipulating expectations or presenting a second pain stimulus.
  
  
  
  The PDR began later after skin heating than electrical stimuli and this is the first examination of the PDR using standard nociceptive testing and manipulations of expectations and competing noxious stimulation.
  
  
  
  A method is described applying PDR to standard heat nociceptive testing, demonstrating stimulus response, reliability, and disruption by cognitive manipulation.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, United States. Electronic address: jimeisenach@gmail.com.
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
authors.forename: Regina
authors.initials: R
authors.lastname: Curry
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Aschenbrenner
authors.affiliation: Division of Anesthesiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Coghill
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Houle
mesh_terms: D000328:Adult; D059031:Anticipation, Psychological / Q000502:physiology; D016477:Artifacts; D003080:Cold Temperature; D003213:Conditioning, Psychological / Q000502:physiology; D003463:Cues; D053483:Eye Movement Measurements / Q000295:instrumentation; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008125:Locus Coeruleus / Q000503:physiopathology; D008297:Male; D009929:Organ Size; D010146:Pain / Q000473:pathology / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods*; D058748:Pain Perception / Q000502:physiology; D011680:Pupil / Q000502:physiology*; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires
keywords: Experimental pain testing; Human study; Locus coeruleus; Pupillometry