Abstract
Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO2 laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.
Highlights
For the past 30 years, investigators have relied extensively on infrared laser stimulators to study nociception and pain perception in humans [1,2,3,4]
CO2 laser stimulation of Ad- and C-fibre afferents Thermal stimuli were applied to the dorsum of the nondominant hand, using a new CO2 laser stimulator whose power is regulated using a feedback control based on an online measurement of skin temperature at the site of stimulation (Laser Stimulation Device, SIFEC, Belgium)
The bimodal vs. unimodal nature of the distribution of reaction times was tested by comparing the fitting of the data to this unimodal function, with the fitting of the data to a bimodal model consisting of the sum of these two functions
Summary
For the past 30 years, investigators have relied extensively on infrared laser stimulators to study nociception and pain perception in humans [1,2,3,4]. As a source of radiant heat applied onto the skin, infrared lasers can be used to activate heat-sensitive Adand C-fibre afferents selectively. Because of their very high power output, infrared lasers can generate the very steep heating ramps required to elicit time-locked responses such as reaction-times and event-related brain potentials [5], and are well suited to study the human nociceptive system. For reasons that remain a matter of debate, brain responses related to the activation of C-fibres can be identified only if the concomitant activation of Ad-fibres is avoided [6,7,8]. In humans, the current research has focussed almost exclusively on characterizing the neural processes triggered by Adfibre input, because of the lack of reliable methods to study the responses triggered by the selective activation of C-fibres. To progress in our understanding of the physiology and pathophysiology of nociception, developing means to study the signals ascending through C-fibres is essential [9]
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