The Genetics of Neuropathic Pain from Model Organisms to Clinical Application

Margarita Calvo, Alexander J. Davies, Harry L. Hébert, Greg A. Weir, Elissa J. Chesler, Nanna B. Finnerup, Roy C. Levitt, Blair H. Smith, G. Gregory Neely, Michael Costigan, David L. Bennett

Research output: Contribution to journalReview article

1 Citation (Scopus)

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. 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 (US)
Pages (from-to)637-653
Number of pages17
JournalNeuron
Volume104
Issue number4
DOIs
StatePublished - Nov 20 2019

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Neuralgia
Clustered Regularly Interspaced Short Palindromic Repeats
Nervous System Trauma
Genetic Techniques
Pain Clinics
Pain
Electrophysiology
Genetic Models
Medical Genetics
Anxiety Disorders
Ion Channels
Neuroimaging
Mutagenesis
Population
Drosophila
Analgesics
Comorbidity
Stem Cells
Therapeutics
Animal Models

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Calvo, M., Davies, A. J., Hébert, H. L., Weir, G. A., Chesler, E. J., Finnerup, N. B., ... Bennett, D. L. (2019). The Genetics of Neuropathic Pain from Model Organisms to Clinical Application. Neuron, 104(4), 637-653. https://doi.org/10.1016/j.neuron.2019.09.018

The Genetics of Neuropathic Pain from Model Organisms to Clinical Application. / Calvo, Margarita; Davies, Alexander J.; Hébert, Harry L.; Weir, Greg A.; Chesler, Elissa J.; Finnerup, Nanna B.; Levitt, Roy C.; Smith, Blair H.; Neely, G. Gregory; Costigan, Michael; Bennett, David L.

In: Neuron, Vol. 104, No. 4, 20.11.2019, p. 637-653.

Research output: Contribution to journalReview article

Calvo, M, Davies, AJ, Hébert, HL, Weir, GA, Chesler, EJ, Finnerup, NB, Levitt, RC, Smith, BH, Neely, GG, Costigan, M & Bennett, DL 2019, 'The Genetics of Neuropathic Pain from Model Organisms to Clinical Application', Neuron, vol. 104, no. 4, pp. 637-653. https://doi.org/10.1016/j.neuron.2019.09.018
Calvo M, Davies AJ, Hébert HL, Weir GA, Chesler EJ, Finnerup NB et al. The Genetics of Neuropathic Pain from Model Organisms to Clinical Application. Neuron. 2019 Nov 20;104(4):637-653. https://doi.org/10.1016/j.neuron.2019.09.018
Calvo, Margarita ; Davies, Alexander J. ; Hébert, Harry L. ; Weir, Greg A. ; Chesler, Elissa J. ; Finnerup, Nanna B. ; Levitt, Roy C. ; Smith, Blair H. ; Neely, G. Gregory ; Costigan, Michael ; Bennett, David L. / The Genetics of Neuropathic Pain from Model Organisms to Clinical Application. In: Neuron. 2019 ; Vol. 104, No. 4. pp. 637-653.
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