Year: 2021
Type: dissertation
Abstract: Aims: A shift in attention away from a painful stimulus can cause pain relief.The mechanisms behind this process are thought to either be fully supraspinal or to involve spinal cord modulation by brainstem nuclei.The main object of investigation of the present thesis is to identify the neural pathways engaged during the attentional modulation of pain in healthy subjects and in patients with chronic pain (fibromyalgia) using functional magnetic resonance imaging.The role of endogenous opioids and of noradrenaline is investigated using selective pharmacology.Methods: In two different studies, healthy volunteers (n=57, Study1) and fibromyalgia patients (n=40, Study2) performed an attentional analgesia experiment during fMRI scanning of brain and brainstem.A third study (n=39, Study3) used an imaging sequence with manual shimming to acquire data simultaneously from brain, brainstem, and spinal cord.The opioid receptor antagonist naltrexone and the noradrenaline re -uptake inhibitor reboxetine are administered to the participants to examine the neurochemical components of attentional analgesia.Results: The attentional task was successful in inducing analgesia in healthy volunteers in all three studies presented.In Study1, a top-down mechanism where the cortex functionally connects to brainstem nuclei was demonstrated.In Study2, attentional analgesia was also observed in fibromyalgia patients, with involvement of similar brainstem mechanisms.In Study3, spinal cord activity mirrored the perceived pain intensity.A cortico-brainstem pathway was shown to modulate the dorsal horn of the spinal cord.Naltrexone blocked this path as well as the analgesic effect behaviourally.Conversely, reboxetine did not influence attentional analgesia.Conclusion: During high cognitive load and concomitant painful stimulation, the descending pain modulatory system, including locus coeruleus and rostroventromedial medulla is recruited for spinal cord modulation.This process is dependent on endogenous opioids.Fibromyalgia patients can achieve attentional analgesia by recruitment of brainstem nuclei, similarly to healthy volunteers. My deepest thanks go to my main supervisors Jon and Tony.Your mentorship guided me through this journey, helping me to grow a lot during the past years.It was very important knowing that I could always count on you.Many thanks to Rosalyn for our long-distance modelling.We have been a great team!Thanks to Lee, Rob, and Wendy for acquiring the data that I could analyse.Special thanks to all the staff in Cric that made all this work possible.Especially, thanks, Aileen, for supporting me during data acquisition and for helping me to find swift solutions at every step
Author: Oliva, Valeria
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7139885187