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Wellcome Trust conference The Challenges of Chronic Pain

11-13 March 2015
Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

Abstract deadline: 30 January 2015
Registration deadline: 16 February 2015

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Europain consortium receives EU and industry funding and begins five year research into better treatments for chronic pain Europain, a public-private consortium funded by the Innovative Medicines Initiative (IMI), announced today the launch of a five-year research project to understand and improve treatment of chronic pain. The project will receive 6MÄ from the IMI as well as 12.5MÄ in kind contribution from the European Federation of Pharmaceutical Industries and Associations (EFPIA) over the coming five years.

One in five adults suffers from chronic pain. This constitutes a major cause of long-term sick leave and forced early retirement, placing a great financial burden on both individuals and healthcare systems. Despite extensive research programmes by biopharmaceutical companies and academia, there remains a need for treatments that are more effective and with fewer side-effects.

Europain has established an international team of leading researchers and clinicians from both academia and industry to undertake multidisciplinary translational research. This team aims to increase the understanding of chronic pain mechanisms, help to develop novel analgesics, and develop better biomarkers for pain. Their ultimate goal is to improve the lives of people suffering from chronic pain.

During the five-year project, Europain will undertake a large number of preclinical and clinical studies. The program will be delivered through collaboration between laboratories in the Europain network, sharing resources to improve the value derived from the budget. Results will be made public during and after the project, ensuring that the knowledge created can be widely applied to the development of better therapies for patients suffering from chronic pain.

Kingís College London, the managing entity of Europain and the academic lead institution will contribute to both the pre-clinical and clinical aspects of the project. One role will be to study the expression of potential pain mediators in both animal models of pain and samples from patients suffering from chronic pain. The role of novel pain mediators will then be investigated using an array of techniques ranging from cell culture to quantitative sensory testing in humans.

Professor Steve McMahon, who along with Dr Dave Bennett will be running the project at Kingís, comments: ĎThere are some big questions facing the pain field at the moment and this consortium, drawing on the skills and expertise of both academia and industry, is in a unique position to address themí.

The consortium network involves scientists representing 12 renowned European Universities: Kingís College London (Academic lead), University College London, Imperial College London, the University of Oxford, the Christian-Albrechts-University of Kiel, the Medical Faculty Mannheim/Heidelberg University, the Technische Universitšt MŁnchen, the Goethe University of Frankfurt, the BG University Hospital Bergmannsheil/Ruhr University Bochum, the University Hospitals of Aarhus, Rigshospitalet Copenhagen, University of Southern Denmark, the SME Neuroscience Technologies from Barcelona, and the research resources and expertise of Europeís most active pharmaceutical companies working in the field of analgesics, including AstraZeneca (co-ordinator), Boehringer-Ingelheim, Eli Lilly, Esteve, Pfizer, Sanofi-Aventis, UCB Pharma.

About the Innovative Medicines Initiative

IMI is a unique Public-Private Partnership (PPP) between the pharmaceutical industry represented by the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the European Union represented by the European Commission.
www.imi.europa.eu.
 
Current Research
Functional Imaging in Persistent Pain Models and Chronic Pain Patients
Functional brain imaging has been used to measure the neural correlates of the subjective experience of pain. Non-invasive imaging methods will be used to understand the central mechanisms involved in pain processing and pain relief in humans. The focus will be to dissect the factors that influence nociceptive inputs to alter pain perception in healthy subjects and in patients suffering from chronic pain.

We will examine specific brainstem nuclei in pro- and anti-nociception during cognitive manipulations and chronic pain states. To achieve this, we will apply high-resolution structural and fMRI as well as diffusion tractography to dissect both the functional and anatomical links between key brainstem nuclei (e.g. PAG, nucleus cuneiformis, RVM, PB) and other sub-cortical and cortical structures during administration of topical capscaicin or a psychological/cognitive manipulation. We will also study post opioid-induced hyperalgesia as a model of non-nerve injury that produces a key symptom of neuropathic pain. We hypothesise that this effect is brainstem mediated via descending facilitation. By identifying pain-related regions in humans on a spatial scale near-equivalent to the functional zones reported from electrophysiological studies in animals, we will generate a tight correlation of findings and hypotheses between the animal and human studies.

We will perform fMRI on cohorts of diabetic neuropathy patients with and without pain and the contribution of central sensitisation and the brainstemís descending modulatory system to their clinical pain investigated using various pain fMRI protocols. The patientís state and trait anxiety levels will be included as co-variates in the analysis; the separate contribution of anxiety to the patientís pain can thus be neuroanatomically determined. Further analyses will investigate whether top-down modulation of brainstem regions via anxiety-driven subcortical structures additionally contribute to pain amplification in patients.

Finally, ongoing tonic pain is a key symptom of chronic pain that is notoriously difficult to model and image either in human models or patients using the conventional Blood Oxygen Dependent Level - fMRI, which requires a change in stimulus input (i.e. pain level) during the experiment. We propose therefore to apply whole-brain cerebral blood flow based-fMRI at two time points when ongoing pain is altered (via normal processes or a drug manipulation) to obtain the neural signature of persistent pain in both our capsaicin model in normal as well as selected chronic pain patients.