The genetics of neuropathic pain from model organisms to clinical application

Calvo, M. et al. (2019) The genetics of neuropathic pain from model organisms to clinical application. Neuron, 104(4), pp. 637-653. (doi: 10.1016/j.neuron.2019.09.018) (PMID:31751545)

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Abstract

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.

Item Type:Articles
Additional Information:D.L.B. is a senior Wellcome clinical scientist (202747/Z/16/Z). D.L.B. is a member of the Wellcome Pain Consortium (102645). D.L.B., N.B.F., and B.H.S. are members of the DOLORisk Consortium funded by the European Commission Horizon 2020 (ID633491). D.L.B. and N.B.F. are members of the International Diabetic Neuropathy Consortium, funded by the Novo Nordisk Foundation (NNF14SA0006). E.J.C. is funded by the NIH NIDA (P50 DA039841). R.C.L. is funded by NINDS NS105880, NS105880-01S1, and 1U01HG010230-01; M. Calvo is funded by Fondecyt Regular 1161019 (National Commission for Science and Technology); and G.G.N. is funded by an NHMRC fellowship and project grants (APP1111940, APP1158164, APP1158165, APP1107514) and by the NSW Ministry of Health. We also acknowledge the support of the Neuropathic pain and Genetics Special Interest Groups of IASP.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Weir, Dr Gregory
Authors: Calvo, M., Davies, A. J., Hébert, H. L., Weir, G. A., Chesler, E. J., Finnerup, N. B., Levitt, R. C., Smith, B. H., Neely, G. G., Costigan, M., and Bennett, D. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Neuron
Publisher:Elsevier (Cell Press)
ISSN:0896-6273
ISSN (Online):1097-4199
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Neuron 104(4): 637-653
Publisher Policy:Reproduced under a Creative Commons License

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