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.
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Funding SchemeSTREP - Specific Targeted Research Project