Pupil responses and pain ratings to heat stimuli: Reliability and effects of expectations and a conditioning pain stimulus

Background: 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. New method: 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. Results: 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. Comparison with existing methods: 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. Conclusions: A method is described applying PDR to standard heat nociceptive testing, demonstrating stimulus response, reliability, and disruption by cognitive manipulation. (C) 2017 Elsevier B.V. All rights reserved.