The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

  • Margarita Calvo, Pontificia Universidad Catolica de Chile
  • ,
  • Alexander J. Davies, Oxford University, Oxford, UK.
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  • Harry L. Hébert, University of Dundee
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  • Greg A. Weir, Oxford University, Oxford, UK.
  • ,
  • Elissa J. Chesler, Jackson Laboratory
  • ,
  • Nanna B. Finnerup
  • Roy C. Levitt, University of Miami Leonard M. Miller School of Medicine
  • ,
  • Blair H. Smith, University of Dundee
  • ,
  • G. Gregory Neely, University of Sydney
  • ,
  • Michael Costigan, Boston Children's Hospital
  • ,
  • David L. Bennett, Oxford University, Oxford, UK.

Neuropathic pain (NeuP) arises due to injury of the somatosensory nervous system and is both common and disabling, rendering an urgent need for non-addictive, effective new therapies. Given the high evolutionary conservation of pain, investigative approaches from Drosophila mutagenesis to human Mendelian genetics have aided our understanding of the maladaptive plasticity underlying NeuP. Successes include the identification of ion channel variants causing hyper-excitability and the importance of neuro-immune signaling. Recent developments encompass improved sensory phenotyping in animal models and patients, brain imaging, and electrophysiology-based pain biomarkers, the collection of large well-phenotyped population cohorts, neurons derived from patient stem cells, and high-precision CRISPR generated genetic editing. We will discuss how to harness these resources to understand the pathophysiological drivers of NeuP, define its relationship with comorbidities such as anxiety, depression, and sleep disorders, and explore how to apply these findings to the prediction, diagnosis, and treatment of NeuP in the clinic. Calvo et al. discuss how applying genetic techniques, from model organisms to human populations, can help us understand the pathophysiology of neuropathic pain. These strategies could soon reveal novel analgesic drug targets and aid both personalized risk prediction and treatment.

Original languageEnglish
JournalNeuron
Volume104
Issue4
Pages (from-to)637-653
Number of pages17
ISSN0896-6273
DOIs
Publication statusPublished - Nov 2019

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