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Bedside to bench and back again, a path to translational pain research?

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If you have a question about this talk, please contact Dr Dervila Glynn.

Theme: Beyond the Neuron: glia, vascular and immune cells

Abstract: Pain has both a sensory and emotional component and is driven by activation of sensory neurones called nociceptors that are tuned to detect noxious stimuli in a process called nociception. Although nociception functions as a detect and protect mechanism. and is found in many organisms, this system becomes dysregulated in a number of conditions where chronic pain presents as a key symptom, for example osteoarthritis. Nociceptors do not innervate empty space though and do not act alone. Going beyond the neurone, other cell types, such as fibroblast-like synoviocytes interact with and modify the function of nociceptors, which is likely a key contributor to the chronification of pain. In this talk, I will look at how combining pre-clinical mouse work with human tissue and genetics might provide a way to accelerate new analgesics from bench to bedside, giving examples from our work in joint pain, bowel pain and labour pain.

Biography: Ewan completed his undergraduate degree in pharmacology at the University of Bath, followed by a PhD at the University of Cambridge working on acid-sensing ion channels. He then moved to work at the Max-Delbrück Centre in Berlin as an Alexander von Humboldt Research Fellow, where he began working on pain peculiarities of the naked mole-rat. This was followed by a 1-year stint at the Skirball Institute of Biomolecular Medicine at NYU as a Max Kade Foundation Fellow, where he worked on CO2 -sensing in C. elegans. In 2013 he was appointed to a Lectureship in Pharmacology at the University of Cambridge where his research group focuses on understanding the molecular basis of nociception using mice, naked mole-rats and human tissue, as well as investigating the cancer resistance and healthy ageing of naked mole-rats. He was promoted to Senior Lecturer in 2017 and Reader in 2019, also being a Fellow of Corpus Christi College and Deputy Head of Department in Pharmacology since 2020. Work in the Smith lab is currently funded by the BBSRC , MRC, Versus Arthritis, Dunhill Medical Trust, Astra Zeneca, Beiersdorf and GSK .

Selected papers
  1. Lee, M., Nahorski, M., Hockley, J.R.F., Lu, V., Ison, G., Pattison, L.A., Callejo, G., Stouffer, K., Fletcher, E., Drissi, I., Wheeler, D., Ernfors, P., Menon, D., Reimann, F., Smith, E.S. and Woods, C.G. (2020). Human labour pain is influenced by the voltage-gated potassium channel KV6 .4 subunit. Cell Reports, 32, 107941
  2. Chakrabarti, S., Pattison, L.A., Doleschall, B., Rickman, R.H., Callejo, G., Heppenstall, P.A. and Smith, E.S. (2020). Intra-articular AAV -PHP.S mediated chemogenetic targeting of knee-innervating DRG neurons alleviates inflammatory pain in mice. Arth Rheum, 72, 1749-1758.
  3. Chakrabarti, S., Hore, Z., Pattison, L.A., Lalnunhlimi, S., Bhebhe, C.N., Callejo, G., Bulmer, D.C., Taams, L.S., Denk, F. and Smith, E.S. (2020). Sensitization of knee-innervating sensory neurons by tumor necrosis factor-α activated fibroblast-like synoviocytes: an in vitro, co-culture model of inflammatory pain. Pain, 161, 2129-2141.
  4. Chakrabarti, S., Jadon, D.R., Bulmer D.C. and Smith, E.S. (2020) Human osteoarthritic synovial fluid increases excitability of mouse dorsal root ganglion sensory neurons: an in-vitro translational model to study arthritic pain. Rheumatology, 59, 662-667
  5. Hockley, J.R.F., Taylor, T.S., Callejo, G., Wilbrey, A.L., Gutterridge, A., Bach, K., Winchester, W.J., Bulmer, D.C., McMurray, G. and Smith, E.S. (2019) Single-cell RNAseq reveals seven classes of colonic sensory neuron. Gut,68, 633-644.

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