Pupil dilation response to noxious stimulation: Effect of varying nitrous oxide concentration

ObjectiveThis report examines the pain-related pupil dilation response (PDR), tracking it across mixture concentrations of nitrous oxide (N2O) in oxygen (O2) and relating its variation to change in long latency somatosensory evoked potentials (SEPs) and visual analogue scale (VAS) pain report.MethodsWe varied mixture concentrations of N2O in O2 (0%, 10%, 30%, and 50%), measuring PDR, SEP and VAS responses to painful electrical fingertip stimulation at high and low intensities in 15 volunteers.ResultsMixed effect model statistical analyses revealed that: (1) PDR increased significantly with stimulus intensity and constricted significantly with mixture concentration; (2) SEP and VAS decreased significantly with increasing mixture concentration; (3) PDR correlated with SEP amplitude and VAS across mixture concentrations; (4) subjects differed significantly in: (a) baseline PDR and SEP amplitudes, (b) rate of change of these measures across mixture concentrations; and (5) VAS increased significantly with stimulus intensity and decreased significantly with mixture concentration without significant individual differences.ConclusionsThe findings support the hypothesis that the pain-related PDR is a complex brain-mediated response rather than a simple sympathetic reflex.SignificancePDR may provide a useful indicator for studying the central processing of noxious stimuli and the effects of analgesic interventions.