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 language | English (US) |
|---|---|
| Pages (from-to) | 637-653 |
| Number of pages | 17 |
| Journal | Neuron |
| Volume | 104 |
| Issue number | 4 |
| DOIs | |
| State | Published - Nov 20 2019 |
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ASJC Scopus subject areas
- Neuroscience(all)
Cite this
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 journal › Review article
}
TY - JOUR
T1 - The Genetics of Neuropathic Pain from Model Organisms to Clinical Application
AU - Calvo, Margarita
AU - Davies, Alexander J.
AU - Hébert, Harry L.
AU - Weir, Greg A.
AU - Chesler, Elissa J.
AU - Finnerup, Nanna B.
AU - Levitt, Roy C.
AU - Smith, Blair H.
AU - Neely, G. Gregory
AU - Costigan, Michael
AU - Bennett, David L.
PY - 2019/11/20
Y1 - 2019/11/20
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85075021373&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2019.09.018
DO - 10.1016/j.neuron.2019.09.018
M3 - Review article
C2 - 31751545
AN - SCOPUS:85075021373
VL - 104
SP - 637
EP - 653
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -