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

• Subject Area: Medicine ; Social and Behavioural Sciences
• Term: since 2015
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 255156212

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.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Silent nociceptors in mice and humans (human-rodent tandem) (Project Heads Lechner, Stefan ;  Schmelz, Martin )
• A03 - Longitudinal analysis of structural and functional changes in peripheral circuits determining the clinical symptoms of painful neuropathies (Project Heads Bendszus, Martin ;  Gangadharan, Vijayan ;  Jende, Johann ;  Nawroth, Peter ;  Pham, Mirko )
• A04 - Interactions between nociceptive and non-nociceptive circuits: intranasal lidocaine to treat primary and secondary headache (Project Heads Carr, Richard ;  Frings, Stephan ;  Hu, Jing ;  Lechner, Stefan ;  Oehler, Beatrice )
• A06 - Functional and structural plasticity following spinal cord injury: contributions to chronic central neuropathic pain (Project Heads Blesch, Ph.D., Armin ;  Bradke, Frank ;  Puttagunta, Ph.D., Radhika ;  Weidner, Norbert )
• A07 - Energy-metabolic interference as novel experimentaltherapeutic intervention for pathological forms of pain (Project Heads Bading, Hilmar ;  Siemens, Jan )
• A08 - Targeting Oat1 and Lrg1 in chronic pain (Project Heads Bading, Hilmar ;  Mauceri, Daniela ;  Ruiz de Almodovar Egea, Ph.D., Carmen ;  Tappe-Theodor, Anke )
• A09 - Glial adrenergic receptors as targets for the treatment of neuropathic pain (Project Heads Agarwal, Ph.D., Amit ;  Kirchhoff, Frank ;  Kuner, Rohini ;  Simonetti, Ph.D., Manuela )
• A10 - Mechanisms of globotriaosylceramide-induced dorsal root ganglion pathology and pain in Fabry disease (human-rodent tandem) (Project Heads Pham, Mirko ;  Sommer, Claudia ;  Üçeyler, Nurcan )
• B01 - Cellular basis and mechanisms underlying the role of the prefrontal cortex in nociception and chronic pain (Project Head Kuner, Rohini )
• B02 - Effects of intranasal oxytocin on the extinction of fear memories in patients and rodent models with chronic pain (Project Heads Ditzen, Beate ;  Grinevich, Valery ;  Herpertz, Sabine C. )
• B04 - Towards a mechanism-specific intervention of thalamo-limbic pain processing (Project Heads Bilbao, Ainhoa ;  Spanagel, Rainer ;  Tesarz, Jonas ;  Tost, Heike ;  Weber-Fahr, Wolfgang ;  Wieland, Sebastian )
• B06 - Modulating oscillatory rhythms and their origins in GABAergic circuitry towards pain relief (human-rodent tandem) (Project Heads Kuner, Rohini ;  Monyer, Hannah ;  Ploner, Markus )
• B07 - Neural circuits involved in phantom limb pain (Project Heads Andoh, Jamila ;  Flor, Herta )
• B08 - Multiscale analysis of structural plasticity in secondary motor cortex (Project Heads Gangadharan, Vijayan ;  Kuner, Thomas ;  Weber-Fahr, Wolfgang )
• B09 - Modulation of brain circuits underlying bidirectional interactions between pain and depression (Project Heads Magerl, Walter ;  Meyer-Lindenberg, Andreas ;  Treede, Rolf-Detlef )
• B11 - Social modulation of chronic pelvic pain: Neural inter-individual co-variation and partner interaction (Project Heads Bilek, Edda ;  Ditzen, Beate )
• S02 - Human pluripotent cell-derived neurons as a tool to study central and peripheral nociceptive mechanisms (Project Heads Acuna Goycolea, Ph.D., Claudio ;  Schrenk-Siemens, Katrin )
• S03 - Multimodal Intervention platform (Project Heads Ahmadi, Rezvan ;  Andoh, Jamila ;  Reininghaus, Ulrich )
• Z01 - Central Tasks (Project Head Kuner, Rohini )
• Z02 - Central data, project and analytics infrastructure (Project Heads Rupp, Rüdiger ;  Schwarz, Ph.D., Emanuel ;  Solinski, Hans Jürgen ;  Weidner, Norbert )

Completed projects

• A02 - Defining the contribution of C-fibre low threshold mechanoreceptors to nociception, acute pain and pain chronicity (Project Head Heppenstall, Paul A. )
• A05 - Characteristics and consequences of subcellular calcium signalling in spinal neurons and glia in chronic inflammatory and neuropathic pain (Project Heads Bading, Hilmar ;  Sprengel, Rolf )
• B03 - The role of learning, stress and underlying brain circuits involving prefrontal-limbic interactions in the development of chronic back pain (Project Heads Flor, Herta ;  Nees, Frauke )
• B05 - The cortical signature of nociception and pain in circuits of the lateral somatosensory system (Project Heads Baumgärtner, Ulf ;  Draguhn, Andreas ;  Rupp, André )
• B10 - Cellular mechanisms of nociception and nociceptive modulation in lateral and medial thalamocortical circuits in mice (Project Heads Groh, Ph.D., Alexander ;  Mease, Ph.D., Rebecca )
• G01 - Thalamic processing of pain and putative control by cortical feedback (Project Head Groh, Ph.D., Alexander )
• S01 - Standardization and development of new pain-related models and methods in rodents and humans (human-rodent tandem) (Project Heads Tappe-Theodor, Anke ;  Treede, Rolf-Detlef )

• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Participating University: Heinrich-Heine-Universität Düsseldorf; Julius-Maximilians-Universität Würzburg; Rheinische Friedrich-Wilhelms-Universität Bonn; Technische Universität München (TUM); Universität Hamburg; Universität des Saarlandes
• Spokesperson: Professorin Dr. Rohini Kuner