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.
N1 - Funding 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 . Figure 4 includes an item from the Servier Medical Art PowerPoint Image Bank under their Creative Commons attribution license.
Funding Information:
D.L.B. acknowledges patent application number PCT/GB2017/052909, D.L.B., J.M. Dawes, G. Weir. Method for the treatment or prevention of pain or excessive neuronal activity or epilepsy. D.L.B. has acted as a consultant on behalf of Oxford Innovation for the following companies: Abide, Amgen, Mitsubishi Tanabe, GSK, TEVA, Biogen, Lilly, Orion, and Theranexus. N.B.F. has served in advisory boards of Grünenthal, Novartis Pharma, Teva Pharmaceuticals, Mitshubishi Tanabe Pharma, Merck, and Mundipharma; has received lecture honoraria from Astellas; and receives a research grant from PAINCARE EU Investigational Medicines Initiative (IMI), where the involved companies are Grunenthal, Bayer, Eli Lilly, Esteve, and Teva. A.J.D. acknowledges patent application number PCT/KR2019/00806. R.C.L. serves as chief scientific officer and board member and is an equity holder Onspira Therapeutics, Inc. and acknowledges patent application number PCT/US18/42122: “Methods for Managing Pain.” G.G.N. acknowledges patent application number AU2018902072A0. M. Costigan receives funding from Amgen.
Funding 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. Figure 4 includes an item from the Servier Medical Art PowerPoint Image Bank under their Creative Commons attribution license. D.L.B. acknowledges patent application number PCT/GB2017/052909, D.L.B. J.M. Dawes, G. Weir. Method for the treatment or prevention of pain or excessive neuronal activity or epilepsy. D.L.B. has acted as a consultant on behalf of Oxford Innovation for the following companies: Abide, Amgen, Mitsubishi Tanabe, GSK, TEVA, Biogen, Lilly, Orion, and Theranexus. N.B.F. has served in advisory boards of Gr?nenthal, Novartis Pharma, Teva Pharmaceuticals, Mitshubishi Tanabe Pharma, Merck, and Mundipharma; has received lecture honoraria from Astellas; and receives a research grant from PAINCARE EU Investigational Medicines Initiative (IMI), where the involved companies are Grunenthal, Bayer, Eli Lilly, Esteve, and Teva. A.J.D. acknowledges patent application number PCT/KR2019/00806. R.C.L. serves as chief scientific officer and board member and is an equity holder Onspira Therapeutics, Inc. and acknowledges patent application number PCT/US18/42122: ?Methods for Managing Pain.? G.G.N. acknowledges patent application number AU2018902072A0. M. Costigan receives funding from Amgen.
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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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 -