Objective Chronic pain undermines the health and welfare of millions of EU citizens and carries enormous financial costs. Individual variability in the burden of pain has traditionally been attributed to psychosocial factors. However, new data indicate that there is an important heritable predisposition to pain, particularly to the development of chronic pain after neural injury (neuropathic pain). Pain susceptibility genes are intrinsically hard to detect in human lineages and populations. We propose the alternative approach of exploiting new rodent models of neuropathy to uncover pain susceptibility loci and associated neurobiological processes, using inbred mouse strains that show high versus low pain phenotype. Linkage analysis and positional cloning, together with expression arrays and a variety electrophysiological and neurochemical methods applied to primary sensory neurons, will be used to identify the biological causes of contrasting pain phenotype. The strategy is to identify genetic and cellular variables that co-vary with pain phenotype across strains. With mouse candidate genes in hand, identification of the human orthologs is feasible. We stress that our project does not aim to find genes that affect susceptibility to specific disease entities that may be painful. Rather, we focus on genes and processes that determine the amount of pain felt by an individual in the presence of a specific disease state or degree of tissue injury. That is, we will investigate pain susceptibility genes rather than disease susceptibility genes. Such genes, and the neural processes with which they are associated, are expected to affect pain intensity irrespective of the proximate cause of the neural damage: trauma, surgery, neoplasm, infection or disease. Results will facilitate the development of novel prognostic, diagnostic and treatment options for chronic pain sufferers, with benefits also for their families, employers and European economies. Fields of science medical and health sciencesclinical medicinesurgerynatural sciencesbiological sciencesbiochemistrybiomoleculesnatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysisnatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomes Keywords nerve injury neuropathy pain Programme(s) FP6-LIFESCIHEALTH - Life sciences, genomics and biotechnology for health: Thematic Priority 1 under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) LSH-2002-2.1.3-8 - Genetics and neurobiology of pain Call for proposal FP6-2002-LIFESCIHEALTH See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator THE HEBREW UNIVERSITY OF JERUSALEM EU contribution No data Address Mt Scopus campus JERUSALEM Israel See on map Total cost No data Participants (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all KAROLINSKA INSTITUTET Sweden EU contribution No data Address Nobels Vaeg 1 STOCKHOLM See on map Total cost No data FRIEDRICH-ALEXANDER UNIVERSITAET ERLANGEN - NUERNBERG Germany EU contribution No data Address Schlossplatz 4 ERLANGEN See on map Total cost No data UNIVERSITY OF PECS Hungary EU contribution No data Address Szanto Kovacs J. u. 1/b PECS See on map Total cost No data SANOFI-AVENTIS DEUTSCHLAND GMBH Germany EU contribution No data Address Industriepark Hoechst, Building G 879 FRANKFURT AM-MAIN See on map Total cost No data