Pediatric chronic pain - proteome-based systems biology

Pain represents a state of enormous physical and psychological stress and is the most common reason for medical advice. Patients with chronic pain are exposed to great suffering. Limited therapeutic efficacy and undesirable side effects are often associated with current therapies for severe and chronic pain. According to the latest estimates, 1.5 million people are affected by chronic pain in Austria, with 50% of them reporting direct impairments in their lives. This explains the immense need for new analgesics and for the development of utterly new therapeutic approaches, which, however, depends on comprehensive basic research into pain and its various manifestations. In particular, we lack knowledge about the differences in chronic pain in childhood compared to adults and also between female and male patients. Knowledge of these differences at the molecular level would enable us to design therapies specifically tailored to these patient groups (i.e., children vs. adults, or female vs. male). This is of high clinical relevance, since the chronicity and severity of pain differs in many aspects in these patient groups, e.g. onset (usually delayed in children), prevalence (often higher in women) and severity (often more severe in women). With regard to these differences, it is the declared goal of our project to identify exactly those changes that occur specifically only in the so-called sensory nerve fibers in the peripheral nervous system (PNS) and only during chronic pain or in certain pain phases. For this purpose we will conduct experiments on mice (males and females) of different ages (children versus adults). We will use an established preclinical mouse model of nerve injury to mimic clinically relevant symptoms of nerve pain (so-called neuropathic pain). Methodologically, we use high-resolution mass spectrometry to reveal dynamic changes in the entirety of proteins (the proteome) during chronic pain and different pain phases. We hope to be able to identify those molecular factors that are important for the different phases of pain. This knowledge lays the foundation for further experiments, in which we will try to manipulate pain in mice by specifically influencing these factors. The results obtained in this way can be used as a starting point for future therapies - after thorough pre- and clinical validation - in order to make the treatment of pain in children more effective and reduce side effects.