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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
Mechanisms of HIV viral envelope protein gp120-induced painful neuropathy
Background
Painful peripheral neuropathy affects approximately 30% of HIV patients. Although the precise aetiology of HIV-associated painful neuropathy is unknown, direct invasion of cells of the nervous system by HIV is unlikely. There is evidence however that the presence of the HIV-1 envelope glycoprotein, gp120, in the peripheral and central nervous systems can initiate a cytokine-driven neurotoxic cascade involving glia and immune cells (Herzberg & Sagen 2001; Milligan et al., 2000;2001). In addition gp120 may directly activate sensory neurons (Oh et al., 2001). Gp120 binds primarily to the CD4 receptor allowing entry of HIV into immune cells. However, gp120 is also a ligand at the chemokine receptors; CXCR4 and CCR5. There is increasing evidence that chemokine receptors are expressed by neurons and glia and that their activation results in pathological responses which may be involved in the development of persistent pain. This project aims to establish a gp120-associated model of peripheral and central neuropathic pain in rodents and to investigate the anatomical and functional basis for this interaction.

Proposed studies
1: Establishment of Behavioural Models of gp120-associated pain.

Behavioural hypersensitivity has been shown to occur in rodents following either intrathecal, or periaxonal administration of gp120 (Minami et al., 2003; Milligan et al.,2001; Herzberg & Sagen, 2001). Based upon these studies, rodent models of HIV related, gp120-induced painful neuropathy are currently being developed involving delivery of gp120 either intrathecally to the spinal cord or perineurally to the sciatic nerve. Initially, behavioural correlates of chronic pain will be assessed in each model employing hind paw withdrawal reflex tests to mechanical, thermal and cold stimulation. Once characterized behaviouraly, the mechanisms of the pain associated with these models will investigated via pharmacological, immunohistochemical and electrophysiological approaches.

2: Development of integrative measurements of chronic pain
In addition to reflex limb withdrawal tests, we are investigating more sophisticated outcome measures for the analysis of integrative pain behaviours. Such paradigms include;
-Place preference and avoidance behavior to mechanical stimuli (LaBuda & Fuchs 2000).
-Weight bearing and paw pressure of injured and contralateral limbs.
-Ultrasound vocalization in response to noxious and innocuous stimuli
-Open field activity to assess exploratory and locomotor behaviour.
-Brush evoked Fos expression (Catheline et al. 1999) which is probably a correlate of the phenomenon of brush evoked dynamic mechanical allodynia, a common feature of clinical neuropathic pain. We will use this approach and ascertain whether such Fos expression can be activated in gp120 treated animals and prevented by pharmacological perturbation.

3: Gene profiling
Dorsal root ganglia and spinal cords from GP120 treated animals will probably be used for studies of differentially expressed genes measured using the microarray facility available to the Consortium. The results will be compared to those obtained from other neuropathic pain models with the intention of identifying differentially expressed genes which are common to neuropathic pain.