Central sensitization increases the pupil dilation elicited by mechanical pinprick stimulation

Abstract

High frequency electrical stimulation (HFS) of skin nociceptors triggers central sensitization, manifested as increased pinprick sensitivity of the skin surrounding the site at which HFS was applied. The aim of the present study was to compare the effects of HFS on pupil dilation and brain responses elicited by pinprick stimulation delivered in the area of increased pinprick sensitivity. In fourteen healthy volunteers HFS was applied to one of the two forearms. Before and twenty minutes after applying HFS, mechanical pinprick stimuli (64 mN and 96 mN) were delivered to the area surrounding the site at which HFS was applied as well as the contralateral control arm. During pinprick stimulation both the pupil size and electroencephalogram were recorded. HFS induced a clear and comparable increase in pinprick sensitivity for both the 64 and 96 mN stimulation intensity. Both pinprick stimulation intensities elicited a greater pupil dilation response when delivered to the area of increased pinprick sensitivity. However, this greater pupil dilation response was larger for the 64 mN compared to the 96 mN stimulation intensity. A similar pattern was observed for the negative wave of the pinprick-evoked brain potentials (PEPs), however, the increase was not significant for the 96 mN and showed only a trend towards significance for the 64 mN. These results show that there is a correspondence between the increase in pupil dilation and the increase in PEPs, but that pupil size is a more sensitive measure for detecting the effects of central sensitization than PEPs.