Mechanistic Dissection of The Attentional Modulation of Pain

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

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.
Date of Award10 Feb 2021
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorAnthony Edward Pickering (Supervisor), Jonathan C.W Brooks (Supervisor) & Rosalyn Moran (Supervisor)

Keywords

  • Pain
  • fMRI
  • attention
  • analgesia
  • brainstem
  • spinal cord

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