CoEN5028 Can a dysfunction of the basal ganglia and related low level nociceptive network underlie some central neuropathic pain symptoms in..

Lead Research Organisation: University of Sheffield
Department Name: Neurosciences

Abstract

Pain is a very common and troublesome, but poorly understood symptom in Parkinson's disease (PD). Central neuropathic pain in PD is often described by patients as otherwise unexplained painful sensations with no apparent origin, predominantly on the more affected side. Central neuropathic pain is thought to originate from a dysfunction of the central nervous system suggesting that the brain circuits that allow us to perceive and process pain could be dysfunctional in Parkinson's disease. While abnormal nociceptive processing has been reported in some cortical structures involved in pain, there is to date no clear pathophysiological mechanism to explain these specific symptoms. Based on our recent discovery of a novel nociceptive network, we propose to test a new hypothesis linking central neuropathic pain symptoms to abnormal activity of this nociceptive network between the basal ganglia, a group of structures known to be dysfunctional in Parkinson's disease, and a primary nociceptive structure within the brainstem, the parabrachial nucleus. We also propose to test whether this network could underlie the beneficial effect of deep brain stimulation of the subthalamic nucleus on central pain symptoms.

Technical Summary

Central neuropathic pain is a common symptom of Parkinson's Disease (PD), which can improve after deep brain stimulation of the subthalamic nucleus (DBS-STN). Both the reason why central neuropathic pain is so common in PD and why DBS-STN helps at alleviating them remains unclear. Our preliminary data suggest that the STN and the nociceptive network to which this structure is linked are dysfunctional, which could contribute to some unexplained central neuropathic pain symptoms in PD. The aim of this project is to assess the involvement of this nociceptive network in central neuropathic pain symptoms in PD as well as elucidating the effect of DBS-STN on this network. For that purpose, we will use a combination of clinical and pre-clinical approaches, namely 1) visualize (fMRI) and quantify (behaviour and electrophysiology) the consequences of painful stimuli in humans (PD patients' vs controls) and rodents (PD rat models vs sham rats) on this network; 2) study the consequences of DBS-STN and optogenetic manipulation of the STN on nociceptive perception and responses in rodents. We expect these complementary technical approaches to address a critical shortcoming in the existing knowledge on underlying mechanisms for pain as one of the most troublesome non-motor symptoms in PD.

Publications

10 25 50
 
Description Pain in Parkinson's disease 
Organisation Newcastle University
Country United Kingdom 
Sector Academic/University 
PI Contribution We are a participating site in a pragmatically orientated, predominantly questionnaire-based UK-wide study on PD pain management.
Collaborator Contribution Jenni Naisby/Newcastle is the PI of this study
Impact no outputs/outcomes so far
Start Year 2022
 
Description Pain in Parkinson's disease 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution Prof Overton and his team are co-applicants on the CoEN award application. Prof Overton will be investigating pain-related mechanisms in an animal model of PD, we will try and parallel these experiments in human patients.
Collaborator Contribution At least monthly meetings with additional advice via email or at ad hoc meetings in between regular monthly meetings. The collaboration with Prof Overton has now expanded to other members of the University of Sheffield with particular expertise in imaging (Prof Jim Wilde) or pain research (Prof Fiona Boissonade).
Impact No specific outputs yet
Start Year 2021
 
Description Alumni event, University of Sheffield 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Annual alumni event of the University of Sheffield, held in London to achieve greater target audience
Year(s) Of Engagement Activity 2022
 
Description Heritage Circle Lunch, University of Sheffield 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact This is a key annual event of the University of Sheffield to which alumni are invited from across the UK. I was given the prestigious honour to update our alumni on our research.
Year(s) Of Engagement Activity 2022