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Modulatory capacity: Understanding individual differences in the relationship between sensory input and pain perception

Final Report Summary - MODULATORY CAPACITY (Modulatory capacity: Understanding individual differences in the relationship between sensory input and pain perception)

The work outlined in my Marie Curie International Incoming Fellowship (IIF) sought to develop a set of brain and behaviour based measuresto characterize individual differences in the ability to adaptively modulate pain. We examined how various potential brain and behavioural markers converge and diverge and characterized the neural mechanisms of various aspects of and individual’s overall pain response. Finally, we aimed to examine whether these measures are associated with cognitive and emotional modulation of pain. The distal goal of the project was to establish a set of measures that could be translated into direct clinical use and to form the collaborations that would facilitate these clinical applications.

To accomplish these aims during the period of my IIFmy laboratory ran three main projects.. The first was the project that formed the core of my original application. 69 participants completed a four session study. We collected static and dynamic quantitative sensory testing, individual differences questionnaires and measrues of cognitive and emotional modulation of pain in all participants. In a subset of 40 participants we also collected resting state and pain evoked functional magnetic resonance imaging.. We observed relationships between individual differences in sensory and emotional responsiveness and connectivity of the brain’s descending modulatory circuitry. These results have been presented at a number of international conferences and two manuscripts are presently being prepared for publication with more expected in the coming months.

During collection of this data, we observed sex and gender differences in some of our measures. To investigate the degree to which this reflected reporting bias or even selective sampling, we enrolled 137 participants in a study examining the degree to which sex and identification with traditional gender roles influenced willingness to participate in a study involving pain and pain responses observed in those individuals who did agree to participate. . We found critical relationships between identification with traditional gender roles and study participation, which suggest that pain studies might not obtain samples that fully represent the range of sex and gender identification groups and that this might, in fact, bias sex differences observed in pain studies. These findings are critically important to understanding individual differences in pain response, particularly insofar as they inform us about generalizability across sex and gender identification.
A final project facilitated bythe support of the IIF is a study of neural pain responses in individuals born with congenital insensitivity to pain. We found that these individuals born without the ability to experience pain had intact neural “pain matrix” responses, indistinguishable from those observed in healthy controls. These results were published in JAMA Neurology and have been featured in Scientific American and Nature Outlooks. Theychallenge how we interpret neuroimaging results of pain, and provide critical context for the use of these tools to obtain “objective markers” of pain within and beyond the research conducted during my IIF..

Findings supported by the IIF have been presented at a number of international meetings (Reading Emotions, 2015; British Pain Society, 2016; International Association for the Study of Pain, 2016) and a number of manuscripts are currently being prepared for peer-reviewed publication.I’ve presented this work in a number of presentations to clinicians and patients. These include the Thames Valley Injuries and Emergencies Specialty Group Meeting (February, 2015), Celebrating Trauma Research in the Thames Valley (January, 2015), Prospect Park and Wrexham Hospital research rounds, and the Fibromyalgia support group at West Berkshire Regional Hospital (June, 2016). I have also disseminated my work in a number of public forums, including Café Scientifique (public outreach event in Reading for British Science Association), U3A (public academic gatherings for Senior citizens) and Maidenhead Skeptics in the Pub. I have scheduled further public talks for June, 2016 (London Skeptics in the Pub) and September, 2016 (Henley Café Scientifique). I have disseminated my work through interviews in print (The Guardian, the Daily Mail, The Nation, The Evening Telegraph etc.) and radio (BBC Berkshire) and in Scientific American.

The IIF has been critical to my integration within the University of Reading (my host institution) and my establishment as an independent scientist. During the period of the IIF, I have been prom In the immediate future we will be conducting analysis to identify aset of behavioural and neuroimaging markers that together characterize emotional and cognitive modulation of pain. We have already begun to develop studies in clinical pain populations that will allow us to directly test the clinical utility of these findings. Work funded by Marie Curie was the core of a joint studentship obtained with the Royal Berkshire Hospital (RBH), focused developing clinical applications for our assessment battery in to predict clinical outcomes in chronic pain. This has allowed us to streamline pain assessment within the hospital and to strengthen collaboration with Dr. Atul Kapila (Anesthetist and Clinical Lead of Research and Development at RBH) and Dr. Deepak Ravindran (Head, Pain Management Unit, RBH). Our first project is to test the utility of the assessment battery in predicting outcomes in patients undergoing total knee replacement. Data gathered as part of the IIF has been vital to funding applications to support this work and will continue to be critical to the development of this long term research program. Building these links has enhanced my integration at the University of Reading and has helped the host in terms of meeting its long term research strategies for building in the area of health related teaching and research, including plans for a Life Sciences building with public facing clinical facilities.

Thus, the project is the first step towards the goal of establishing a set of brain and behaviour based markers for development of chronic pain and treatment response. The support of the IIF has not only been vital in collecting data to support future work, but in allowing strong integration into the host institution, facilitating new partnerships and establishing myself as an independent scientist. During the period of the IIF I was promoted to associate professor and have obtained external funding and built new collaborations. This has positioned me to begin examining how these measurement techniques can be used to identify individuals at high risk of developing chronic pain ad possibly how early interventions might mitigate this risk.