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

- Acute changes in pupil diameter reflect changes in locus coeruleus activity.
- Pupil dilation occurs in response to noxious stimulation, but the effect of heat stimuli on pupil response has not been tested.
- In volunteers, pupil dilation correlates with heat temperature and with pain intensity.
- The relationship between pupil dilation and pain intensity report is disrupted when cognitive load is increased.

BackgroundThe 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 methodHealthy 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.ResultsA 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 methodsThe 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.ConclusionsA method is described applying PDR to standard heat nociceptive testing, demonstrating stimulus response, reliability, and disruption by cognitive manipulation.