B3597 - Resilience and Susceptibility to Chronic Pain in ALSPAC - 28/08/2020

B number: 
Principal applicant name: 
Anthony Pickering | University of Bristol (United Kingdom)
Dr Jim Dunham, Dr Jon Brooks, Dr Tom Lancaster, Dr. Laura Corbin, Dr. Laura Howe, Prof. Christopher Eccleston, Prof. Rachael Gooberman-Hill, Prof. Emma Robinson, Prof. Ian Penton-Voak
Title of project: 
Resilience and Susceptibility to Chronic Pain in ALSPAC
Proposal summary: 

Pain which lasts for more than 3 months is termed chronic or persistent pain. It often occurs in the absence of obvious injury. It can be very difficult to treat. The UK is home to several large databases that contain information about subjects’ life history of pain and their genetic “make-up”. We plan to use the largest of these (UK Biobank) to help identify the genes that are related to the presence of a chronic pain condition (e.g. pain of duration >3 months) and the related symptoms experienced by sufferers e.g. low mood, poor sleep, lack of motivation, (pain) anxiety or pain depression. By gaining confidence that these genetic markers are related to the presence of a chronic pain condition, we will then use this information to recruit two small (each <200) groups of ALSPAC subjects who may or may not already have a pain condition. The beauty of this approach, is that by identifying the genes that make people susceptible to developing a pain condition, we will see how this interacts with health factors e.g. weight, blood pressure, and events that shape a person’s psychology e.g. adverse life events such as bereavement, to try to provide a means for people to modify their risk, or identify people for whom early intervention might be most beneficial following an injury – to hopefully avoid them going on to suffer life-long pain.

To achieve this goal, we would ask those subjects to undergo a series of pain tests (which of themselves cause only temporary discomfort) and undergo an MRI scan of their brain and spinal cord.

To better characterise pain present in the ALSPAC cohort, we propose to add pain-specific questionnaires (and tasks) to the upcoming age 30 clinics and questionnaires, which would target all participants. These questionnaires/tasks would explore the incidence of pain in the cohort, which will provide a more complete picture than is currently available. By adding information to this time point, we will gain insight to the cohort and to which genetic and biological factors can influence the development of a chronic pain condition. The availability of this window, where the majority of the cohort are still (hopefully) pain-free, will provide a baseline from which future studies will be able to reflect on the factors that ultimately led some participants to develop a chronic pain condition.

Impact of research: 
1. Defining a polygenic risk score for chronic pain, if validated, will aid in the future delivery of personalised patient care. 2. The PRS with MR PheWAS can suggest causality and directionality enabling better understanding of the complex relationships between pain and psychosocial influences. 3. The recall arm will determine if high and low risk individuals, identified via the PRS, have altered pain processing in the absence of chronic pain. This will informed understanding on the development of chronic pain and could well aid in delivery of personalised patient care. 4. Inclusion of a set of standard pain (and pain related) questionnaires within the ALSPAC cohort will create a resource to the pain community of international importance.
Date proposal received: 
Friday, 14 August, 2020
Date proposal approved: 
Tuesday, 18 August, 2020
Genetic epidemiology (including association studies and mendelian randomisation), Pain, As described above: PRS and MR-PheWAS QST, CPM and Imaging New Questionnaires, Genetic epidemiology