AN EEG INVESTIGATION OF PAIN PROCESSING IN PARKINSON’S DISEASE

Abstract

Chronic pain in Parkinson’s disease (PD) is significantly higher than in the general population, and is often overlooked to be a side effect of the impaired movement and stiffness associated with the disease. There is scientific rational to link the degeneration which occurs in the PD brain to the increased prevalence of chronic pain. Although acute pain thresholds have been shown to be lower in PD, there is a lack of neuroimaging research which investigates the role of central processing in PD. Therefore, this thesis documents one of the first neuroimaging studies to investigate whether central pain processing is abnormal in people with PD. The perception of pain can be modulated by subject driven processing such as attention, salience assignment and cognition, which is regarded as top-down modulation and is often abnormal in chronic pain conditions. A technique to investigate top-down processing is to study the neural activity during the anticipation of acute pain stimulus. Hence, in this thesis, we used EEG to record the anticipatory response to acute pain stimuli delivered by a CO2 laser. Our first experiment compared people with PD whilst off their medication to a healthy age-matched cohort and concluded that the PD patients showed an amplified anticipatory response and a higher sensitivity to the laser. In contrast, following dopamine increasing medication, no difference was shown between the PD and healthy controls. To investigate the role of dopamine in altering pain perception in PD, the second study investigated the effect of manipulating the dopamine D2 receptor in young healthy volunteers. The study reported that the agonist and antagonist induced reductions in neural activity in the parietal and temporal lobes during pain perception, and the antagonist induced a reduction in the activity of the insula during pain perception, and intensified the effect of certainty during anticipation on the rating of pain. The patient and the D2R manipulation studies demonstrated that dopamine may play a role in the top-down processing of pain and hence explain why chronic pain in PD is prevalent. Importantly the pain rating and sensitivity were not changed by Levodopa administration or D2R manipulation and supports the notion that dopamine is central to modulating top-down processing, rather than directly coding the intensity of pain. Therefore, together with further neuroimaging research conducted during the PhD, there is strong evidence of a disruption in the central processing of pain in PD and promotes the use of alternative therapies in the treatment of chronic pain in PD.

Date of Award	31 Dec 2019
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Anthony Jones (Supervisor), Christopher Kobylecki (Supervisor), Christopher Brown (Supervisor) & Monty Silverdale (Supervisor)