The sensory and affective components of pain differentially shape pupillary dilatation during cold pressor tests

Nociceptive and affective stimuli increase reflex sympathetic outflow to the pupils. To investigate effects of stimulus intensity, unpleasantness and distress on these pupillary reflexes, and to assess their stability, healthy participants immersed their hand in ice-water three times (for 20, 40 and 60 s; or 60, 40 and 20 s; or three times for 60 s) (N = 21 in each condition). Each ice-water immersion was preceded by a 90 s warm water immersion. To evaluate phasic sympathetic influences on pupil diameter, pupillary re-dilatation after 1 s of bright light was assessed during the last 10 s of each immersion. By-and-large, pain ratings and pupil diameter were greater during longer than shorter ice-water immersions, and ice-water immersions facilitated pupillary re-dilatation after the flash stimulus. However, mean pupil diameter during ice- and warm water immersions, minor ipsilateral amplification of the pupillary response, and ratings of pain unpleasantness and distress decreased across the experiment. Together, these findings suggest that nociceptive input increased sympathetic pupillary tone and amplified phasic increases in sympathetic activity after exposure to light. However, tonic sympathetic influences on pupil diameter and lateralization decreased across repeated immersions, possibly as novel or threatening aspects of the experience declined. Pupillary nociceptive and affective reflexes involve the locus coeruleus, an integral component of neural circuits that heighten cortical arousal and regulate pain. As these reflexes appear to reflect different aspects of sensory and affective processing, their combined assessment might increase the sensitivity and specificity of tests of locus coeruleus function in patients with suspected deficits.