Consortium Against Pain inEquality (CAPE) - The impact of adverse childhood experiences on chronic pain and responses to treatment

Adverse childhood experiences (ACEs) include physical or emotional abuse, neglect, and domestic violence. The World Health Organisation describes ACEs as the commonest and most intense childhood stressors. About half of us may endure at least one, but children exposed to several are likely to have more health problems later in life, including chronic pain. There are links between exposure to multiple ACEs and social deprivation and the likelihood of ACE exposure is higher for boys, and for children of a young mother. Although there is good evidence that ACEs contribute to health inequalities, there is no widespread screening or systematic approach to reducing long term harms. Reasons for this include limitations in existing assessment approaches, and little consideration of other factors that might increase vulnerability.

Our CAPE consortium will bring together people from a wide range of backgrounds- such as scientists, people with lived experience of ACE and chronic pain, clinical researchers, epidemiologists and psychologists. We will use an inclusive approach to integrate biological, psychological, social and cultural factors to understand the impact of ACE on chronic pain and how people respond to treatment. There are 5 related work packages:

1. We aim to develop a questionnaire-based assessment that captures ACEs. We will analyse current approaches to see which ones work best. Alongside this we will use people's first-hand accounts, to ensure that lived experiences of ACEs and chronic pain, are accurately reflected in our approach. Working with patient partners we will bring together this information to develop and test a new ACE questionnaire (the CAPE ACEQ).
2. The CAPE ACEQ will be used to enrich pre-existing data in large scale population research datasets, (e.g. UK Biobank). We will also collect data about pain and social interactions (adult relationships). We will link this to prescribing, health records (including mental health) to identify psychosocial factors that create vulnerability to chronic pain and adverse responses to treatment in those exposed to ACEs. We will examine whether the increased burden of chronic pain, which disproportionately affects those exposed to multiple ACEs, leads to higher levels of opioid prescribing and associated adverse events observed in deprived communities.
3. We will collect similar data on pain, its impact (mood, sleep, fatigue etc), ACEs, health and social factors from a large group of young patients suffering from a condition called juvenile idiopathic arthritis (JIA), who attend a specialist unit in London. We will be able to understand what factors lead to different pain routes and outcomes in these young people.
4. We will use brain imaging data from the existing population studies and new brain imaging from the young JIA group, to establish whether there are changes in brain structure and/or function that may be associated with the development of poor pain and prescribing outcomes in those exposed to ACEs.
5. We will seek biological markers of vulnerability or resilience to chronic pain and treatment in those exposed to multiple ACEs. For this we will study genetic factors, and test properties of brain cells, from donated samples. Participants in a population study called the Lothian Birth Cohort will be asked about their exposure to ACEs. Many have consented to donate brain tissue post-mortem and have already provided blood for the production of pluripotent stem cells. These special cells will be differentiated to form brain cells.

We anticipate that high quality evidence linking ACEs to chronic pain and treatment outcomes, combined with knowledge of mental health and social support, will provide a basis to develop individualised approaches to pain management and identify public health interventions to improve outcomes.

The WHO describes adverse childhood experiences (ACEs) as the commonest and most intense childhood stressors. About 50% of people experience at least one and those exposed to several are more likely to suffer health problems later in life, including chronic pain, misuse of pain medications and polysubstance dependence. Recent evidence in young people suggests that ACEs are associated with an exposure-dependent increase in the prevalence of chronic pain. ACEs are emerging as leading contributors to multiple health disparities, disproportionately affecting the poorest in society. However, although there is increasing recognition that ACEs contribute to health inequalities, there is a lack of widespread screening, which might otherwise enable stratified health interventions. There are several reasons for this including inconsistencies regarding ACE assessment and poor understanding of additional factors that may contribute to vulnerability to ACE exposure.
The aim of CAPE is to determine whether exposure to ACEs, contributes to inequalities in chronic pain, its treatment and adverse outcomes of opioid analgesics, influenced by vulnerabilities to early life stress. In consultation with our patient advisory group (PAG), CAPE will:

1) Develop a comprehensive tool for assessing the impact of ACEs on chronic pain and its treatment
2) Enrich existing large population cohort data, examining associations between ACE exposure, adverse events in adulthood, chronic pain and opioid analgesic treatment in those exposed to ACEs
3) Examine associations between ACE exposure and divergent pain trajectories in a deeply phenotyped juvenile idiopathic arthritis patient cohort
4) Establish neuroimaging markers of vulnerability/resilience to chronic pain in those exposed to ACEs
5) Identify biomarkers of vulnerability/resilience to chronic pain in those exposed to early life stress