Other - Mechanisms

From Cells to Humans’ Pain (and Back) – Translational Pain Research is More than Just a Vision

This workshop will provide a lively discussion about possible ways to approach translation pain research by three protagonists within this field. Each of the three presenters will give a brief overview about their way of performing translational pain research. Cheryl Stucky will talk about her recent translational approaches by using rodent models of chronic pain including inflammation, nerve injury and diseases associated with devastating pain. Her focus lies on the understanding of how ion channels on pain-sensing neurons contribute to pain, e.g. to pain of specific origin. Esther Pogatzki-Zahn will provide improvement in translational research related to acute and chronic pain after surgery, for example by improving rodent postsurgical models, using multidimensional pain behavioral approaches, unbiased proteomic studies and performing parallel studies in rodents and humans. Theodore Price will talk about his recent single-cell transcriptomics on mouse and human tissues (nociceptors and spinal cord neurons); here he comprehensively categorized similarities and differences between mouse and human cells and identified potential drug targets based on unbiased transcriptomic enrichment analysis of the human DRG and spinal cord. A discussion with the audience will focus on how the future of translational pain research will look like and research agenda should/could look like.

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Advances in Translational Pain Research Related to Acute and Chronic Pain After Surgery: Parallel Experiments in Specific Rodent Pain Models, Humans and Patients

Preclinical disease-specific pain models in rodents are essential to advance our knowledge about mechanisms inherent in pain caused by specific conditions. One example is pain after surgery; rodent plantar incision models have been developed quite some years ago and have revealed that mechanisms inherent in pain after incision injury differ significantly from those mechanisms inherent in other pain conditions.This talk will present recent finding using these plantar incision models as well as major advancements in the field of translational postoperative pain research. First, the role of more procedure specific surgical models and the assessment of multidimensional pain-related behavior to increase the translation of preclinical findings to the clinic will be discussed. Furthermore, parallel studies in rodents, preclinical human incision models and in postoperative patients will be presented; examples here are gender- specific aspects and the role of sex hormones, beyond others. Finally, ongoing studies combining extensive phenotyping with quantitative proteomics in mice and humans enabling the detection of interspecies similarities and differences between mouse models and human subjects will be discussed. At the end a perspective how to identify protein networks relevant for acute and chronic pain after surgery in patients will be shown.

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Using Human Molecular Neuroscience to Increase the Translational Potential of Preclinical Pain Research

Dr Price will discuss his lab’s work on profiling single cells in the human DRG and spinal dorsal horn and how this compares to mice. He will focus on how this new information can be used to focus on targets that are most translationally relevant. He will also discuss how pain assays can be developed using human DRG and spinal cord to build target validation in human tissues into therapeutic development programs.

 

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Innovations and Advances in Modelling and Measuring Pain in Animals and Comparisons to Humans

The translation of analgesic drug candidates to the clinic relies upon successful preclinical pain modelling. Dr. Stucky will discuss best practices for modeling persistent and chronic pain through choosing the most “face valid” animal models and pain behavior assays. Four fundamental decisions apply to every pain behaviour experiment: choice of subject (model organism), choice of assay (pain-inducing injury), laboratory environment and choice of outcome measures. She will discuss pros and cons of each of these four factors in making these choices. In addition, she will discuss how the use of human tissues (e.g. dorsal root ganglia, skin and plasma) which are increasingly accessible, can be used to validate the translatability of targets and mechanisms identified in animal pain models. The translation of analgesic drug candidates to the clinic relies upon successful preclinical pain modelling. Dr. Stucky will describe recent trends in the methods used to model pain in laboratory animals and provide recommendations for experimental designs that may increase translational success.

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