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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 6M€ from the IMI as well as 12.5M€ 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.

King’s 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 King’s, comments: ‘There 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 them’.

The consortium network involves scientists representing 12 renowned European Universities: King’s 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 Universität München, 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 Europe’s 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.
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Past Research
Using RNA interference to study the role of potassium channels in neuropathic pain
One of the main mechanisms for the emergence of neuropathic pain is increased spontaneous activity of neuronal components in the nociceptive pathway. Ion channels are undoubtedly implicated in the determination of a neuron?s intrinsic electrical activity and therefore their ability to generate high frequencies of action potentials. Research has traditionally focused on a number of sodium channels, mainly Nav1.7, Nav1.8 and Nav1.3, as candidates responsible for the increased ectopic activity seen in chronic pain. Recent data however indicates that mice lacking these genes develop neuropathic pain normally.

Potassium channels have mainly been explored as drug targets to reverse chronic pain symptoms by reducing the excitability of the affected neurons. Although there is circumstantial evidence for a role of a number of voltage-gated potassium channels (Kv) in chronic pain, definitive evidence is lacking. Our hypothesis is that reduced expression of Kv channels can contribute to the development of neuropathic pain, by mediating increased neuronal ectopic activity.

Our potassium channel targets are derived from a microarray study that demonstrated down-regulation of voltage-gated potassium channels (Kv) in a peripheral nerve injury model. Some of the candidates encode functional channels with widespread distribution in the nervous system, while others are electrically silent but encode subunits that potentially regulate other Kv channels. Elucidation of how the interaction and relative expression levels of Kv subunits influence neuronal excitability and promote ectopic activity, could be a significant advance in our understanding of the genesis of pain.

We aim to experimentally induce a similar down-regulation by using non-integrating lentiviral vectors encoding shRNAs against these targets. These vectors are safer for clinical applications and in preliminary experiments have been shown to efficiently transfect neuronal cells in vitro and in vivo, featuring prolonged expression as well. After validating the microarray data by RT-PCR, we will use such vectors to transfect DRG neurones in culture and down-regulate the expression of the genes of interest. The hypothesis is that this will allow us to simulate components of neuropathic pain. Co-transfection experiments with vectors encoding shRNAs against different Kv subunits will allow investigation of the synergistic effect of Kv current suppression. Cellular biology experiments will determine subunit interactions, patterns of localisation and how these are altered by the relative expression of the component subunits. Calcium imaging and patch-clamping of cultured neurons will explore how differential Kv expression influences the intrinsic neuronal excitability. Provided that the lentiviral vectors prove efficient for the knocking-down of genes in cells of interest, the experiments will be extended to the living organism. Electrophysiology and behaviour techniques will attempt to correlate electrical activity with pain phenotype.