Latent enhancers - a novel mechanism for pain chronification?

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All of us are likely to know someone that suffers from chronic pain - it is a very common condition, which can be caused by sports injuries, various diseases and the process of ageing. Treatment options are limited, and doctors are often unable to offer anything more than partial relief with a prescription of painkillers, leaving their patients resigned to suffering.While chronic pain can have many different causes, the outcome is often the same: an overly sensitive nervous system which responds much more than it normally would. However, a question still remains as to why the nervous system should remain in this sensitive state over long periods of time, especially in instances where the underlying injury or disease has gone.This grant seeks to investigate this paradox. It is based on findings that nerve damage can change epigenetic marks on some of the genes in immune cells that are known to be important for the generation of persistent pain. Epigenetics is the process that determines which gene is expressed and where. Some epigenetic signals have direct functional consequences, while others are just primers: flags that indicate a potential to act or be modified. This grant is designed to investigate this phenomenon further: we would like to find out whether a chronic pain state alters epigenetic marks not only in immune cells, but also in neurons, and we would like to investigate the functional consequences of these alterations. Our overall hypothesis is that the many small injuries we encounter over our lifetimes - innocuous in isolation - might leave a plethora of molecular 'footprints', which can add up to more lasting damage, and ultimately chronic pain.