EVALUATION COMMITTEE

The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture: 

• Dr. Francesca Fardo, Center of Functionally Integrative Neuroscience & Danish Pain Research Center, Aarhus University, Denmark
• Dr. Wolfgang Greffrath, University of Heidelberg, Germany
• Dr. Laura Petrini, HST, Aalborg University, Denmark (Chairman).

Moderator: Dr. Ken Steffen Frahm, Health Science and Technology, Aalborg University

ABSTRACT

The nociceptive system, which is responsible for detecting and responding to noxious or potentially harmful stimuli, plays a critical role in protecting the body from harm and alerting us to potential dangers. The nociceptors are located throughout the body and are particularly innervated in the skin, muscles, and internal organs. To investigate the processing of pain information through the nociceptive system, noxious stimuli are employed to activate myelinated Aδ fiber and unmyelinated C fiber nociceptors. Various types of noxious stimuli have been utilized to activate cutaneous nociceptors including mechanical, electrical, pressure, heat, cold and chemical stimuli. Most of these stimulation modalities need to be in mechanical contact with the stimulation site which leads to the activation of mechanoreceptors in addition to nociceptors. Removing the co-activation of mechanoreceptors allows for a more precise investigation of pain processing mechanisms and underlying neural pathways engaged. Over the past 4 decades, laser stimulators have gained attention in pain studies due to their capability to selectively activate cutaneous nociceptors. Lasers also provide non-contact stimuli which allow entirely thermal stimulation without coactivating mechanoreceptors. However, the difficulty of thermal laser stimulation is to make sure uniform activation of cutaneous nociceptors, which is possible by controlling the skin temperature during stimulation. Typically, the intensity of stimulation has been controlled using an open-loop approach (i.e. using fixed laser power), however, some studies implemented closed-loop control for stationary laser stimuli to provide low-temperature variations. While these stationary closed-loop control systems provide valuable information about temporal and spatial mechanisms, it is still missing the combined tempo-spatial information. To probe the combined tempo-spatial mechanisms of the nociceptive system, it is necessary to employ a stimulation system that enables displacement of the laser beam across the stimulation area. Moving stimuli allow for the investigation of tempo-spatial acuities such as directional discrimination, which have not been studied in a closed-loop system. Therefore, using a displaceable closed-loop system helps us investigate directional discrimination more accurately and how it can be improved within subjects.

The principal purpose of this Ph.D. project was to investigate the tempo-spatial integration of pain information in the nociceptive system, using directional discrimination. To this end, a novel displaceable closed-loop, temperature-controlled laser stimulation system was developed to provide a more accurate investigation of directional discrimination. The displaceable closed-loop laser stimulation system was implemented, tested and validated (Study I). This stimulation system was then employed to investigate tempo-spatial acuity in the nociceptive system using directional discrimination (Study II). Finally, it was investigated if directional discrimination can be improved by perceptual learning (Study III).

The results of Study I showed that the closed-loop laser stimulation system was capable to reduce the variability of perceived stimuli during a movable stimulus. Study II showed that the variability of directional discrimination decreased using closed-loop stimulation which means the obtained directional discrimination threshold is more reliable compared to open-loop control. Finally, Study III revealed that perceptual learning could improve directional discrimination, indicating that tempo-spatial acuity in the nociceptive system could be improved by learning.

Therefore, the new developed displaceable closed-loop control system could provide a reliable tool for pain studies to deliver more uniform activation of nociceptors. This control system can be extensively employed in the nociceptive system to have a more accurate investigation of how nociceptive information can be integrated.