PAiNMSK

Tissue injuries of various origins induce inflammation and this in turn causes inflammatory pain which is characterized by hypersensitivity to heat and mechanical stimuli. Inflammatory pain is most often prolonged, lasts until complete recovery, or in the absence of such recovery, even persists for more than six months. Pain of inflammatory origin affects about 50 percent of people at some point during their life. Yet, effective relief of inflammatory pain is an unmet medical need. We have reported recently that particular proteins within the cellular nucleus (the enzymes mitogen and stress-activated kinase (MSK) 1 and MSK2) are important for the process leading to heat hypersensitivity in inflamed tissue. In our preliminary studies we found that in particular MSK 1 is the principal isoform responsible inflammatory pain and specifically acts in a group of pain sensing neurons. Mechanisms involved in the development of inflammatory pain must be identified to develop new mechanisms-based and effective analgesics. We will scrutinize MSK1s role in the development of heat hypersensitivity and elucidate how MSK1-dependent molecular mechanisms contribute to the development and persistence of inflammatory pain. In an international collaboration between a Hungarian (Debrecen University) and an Austrian (Medical University Innsbruck) university, an integrated and multidisciplinary approach will be used to construct the MSK1-dependent molecular network and identify hub molecules responsible for the development of inflammatory heat hypersensitivity. Emerging data will provide mechanistic insight how the MSK1-controlled molecular events in pain sensing neurons lead to the development of inflammatory heat hypersensitivity and identify novel targets for drug development.

Tissue injuries of various origins induce inflammation and this in turn causes inflammatory pain which is characterized by hypersensitivity to heat and mechanical stimuli. Inflammatory pain is most often prolonged, lasts until complete recovery, or in the absence of such recovery, even persists for more than six months. Pain of inflammatory origin affects about 50 percent of people at some point during their life. Yet, effective relief of inflammatory pain is an unmet medical need. We have reported recently that particular proteins within the cellular nucleus (the enzymes mitogen and stress-activated kinase (MSK) 1 and MSK2) are important for the process leading to heat hypersensitivity in inflamed tissue. In our preliminary studies we found that in particular MSK 1 is the principal isoform responsible inflammatory pain and specifically acts in a group of pain sensing neurons. Mechanisms involved in the development of inflammatory pain must be identified to develop new mechanisms-based and effective analgesics. We will scrutinize MSK1's role in the development of heat hypersensitivity and elucidate how MSK1-dependent molecular mechanisms contribute to the development and persistence of inflammatory pain. In an international collaboration between a Hungarian (Debrecen University) and an Austrian (Medical University Innsbruck) university, an integrated and multidisciplinary approach will be used to construct the MSK1-dependent molecular network and identify hub molecules responsible for the development of inflammatory heat hypersensitivity. Emerging data will provide mechanistic insight how the MSK1-controlled molecular events in pain sensing neurons lead to the development of inflammatory heat hypersensitivity and identify novel targets for drug development.