SFB 1158: From nociception to chronic pain: Structure-function properties of neural pathways and their reorganisation

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Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle has been that the nature of neural circuits underlying the complex, multidimensional experience of pain is not well understood and the diverse maladaptive plasticity processes that accompany pain chronicity have not been decoded in terms of underlying mechanisms and functional relevance. Importantly, interrelationship of chronic pain with anxiety, fear and depression, which worsen prognosis is still not understood. The primary goal of this consortium is to understand structure-function properties of cells, circuits and networks that impart specificity to the perception of pain and to address how these are altered during the transition from acute to chronic pain. Importantly, the consortium encompasses animal models of chronic pain as well as chronic pain patients and strives to implement translational measures to use the knowledge gained towards deriving new therapeutic principles. Our structure-function analyses conducted over the first funding period elucidated the differential contributions of specific regions, pathways and particular activity rhythms to the generation and maintenance of chronic pain. Our detailed mechanism-oriented analyses in the second funding period uncovered cellular determinants, molecular mechanisms and genetic/epigenetic regulation in plasticity of neurons and glia in the transition from acute to chronic pain, and revealed the basis of psychological, social and environmental influences on pain perception. With these deep mechanistic insights gained thus far, we now propose to place a particular focus on optimizing existing therapies for chronic pain by elucidating neural circuits and mechanisms underlying therapeutic effects and identifying predictive biomarkers associated with pain relief. Moreover, we aim to develop innovative strategies for new therapeutic interventions in chronic pain. Our analyses will span pharmacological and gene therapy approaches, different types of neuromodulation/neurostimulation and sensory-motor paradigms, virtual reality applications, cognitive behavioural and social interventions as well as digital diagnostics and interventions. Translationally-oriented supporting projects, including in vitro human cellular model systems, an in vivo interventional platform and a central data infrastructure project, will assist rodent-, human- and human-rodent tandem projects. Via this strategy, the CRC seeks to generate mechanistic and unique knowledge as well as concrete strategies for defeating chronic pain and associated suffering.