EVALUATION COMMITTEE

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

• Associate Professor Diana M. Torta, Faculty of Psychology and Educational Science, Leuven
• Associate Professor Valéry Legrain, Université catholique de Louvain, Belgium
• Associate Professor Sabata Gervasio, Aalborg University, Denmark (Chairman)

Moderator: Professor Thomas Graven-Nielsen, Aalborg University, Denmark 

ABSTRACT

Chronic pain is one of the major causes of disability worldwide, yet its treatment and management remain limited. A pivotal step for arriving at an adequate treatment is an adequate understanding of chronic pain pathophysiology from its basic mechanisms. In this matter, research has shown that functional and structural reorganization of the sensorimotor cortex contributes to the chronic pain percept. This reorganization is thought to be enabled by synaptic plasticity which drives neuronal changes in a positive feedback mechanism through long-term potentiation and long-term depression. However, if this positive feedback mechanism had no restriction, the system would risk entering an excessively increased or decreased excitability state. Thus, homeostatic plasticity comes into play as a stabilizing mechanism that limits cortical excitability within a physiological range.

Homeostatic plasticity can be researched in the healthy human brain with two blocks of non-invasive brain stimulation. A reliably tested homeostatic response has been observed in healthy volunteers as a reversal of excitability (i.e., decreased amplitude) in motor-evoked potentials after an excitatory-excitatory protocol. This is not the case for states of chronic or experimental pain, where the homeostatic plasticity response is impaired. The alteration of corticomotor homeostatic plasticity during pain suggests that this mechanism may have a significant role in nociceptive physiology. Nonetheless, research on homeostatic plasticity regarding pain remains unclear, as there are yet no studies that have explored whether the sensory and nociceptive domains demonstrate a similar homeostatic plasticity response. The first aim of this PhD project was to investigate if the sensorimotor cortex (S1) demonstrated a homeostatic-like response through somatosensory evoked potentials (SEPs) after inducing homeostatic plasticity in M1. The results of this first study indicate that SEPs were facilitated after the M1 homeostatic plasticity protocol, but no homeostatic-like response was found. Therefore, confirming the initial hypothesis, that the role of homeostatic plasticity may not be intrinsically related to sensation, but to nociception. Consequently, the second aim of this PhD was to assess whether the nociceptive response would have a homeostatic-like behavior after M1 homeostatic plasticity induction. For this, an experiment was designed where there was a pain-free session and a capsaicin-induced pain session, to study whether any homeostatic-like effect would be impaired in the presence of pain. The results of this study suggest that the early lateralized N1P1 pain-related evoked potential (electrically induced with the pin electrode) showed a homeostatic-like response after the homeostatic plasticity induction over M1. This response was impaired during capsaicin-induced pain. Furthermore, capsaicin-induced pain decreased the lateralized N1P1 component away from the secondary area of hyperalgesia. The N2P2 vertex potential did not show any changes except habituation. In sum, the findings of this second study suggest that homeostatic plasticity may play a role in the early nociceptive input response. Finally, the third study aimed to confirm the latter findings with a more specific stimulation for the Adelta fibers (contact-heat evoked potentials), and to test whether changing the target of homeostatic plasticity induction from M1 to S1, would change the homeostatic-like response during pain and pain-free state.

To summarize, the methodologies and findings of this PhD show an important first step in translating the well-studied M1 homeostatic plasticity knowledge and relating it to the less-known S1 and nociceptive response. These findings aim to contribute to the basic understanding of chronic pain pathophysiology and its disturbed plasticity mechanisms.