Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.
GWAS
central sensitization
in vivo calcium imaging
in vivo electrophysiology
pain
spinal cord
temporal summation
wind-up
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
17 08 2022
17 08 2022
Historique:
received:
22
09
2021
revised:
31
03
2022
accepted:
16
05
2022
pubmed:
16
6
2022
medline:
23
8
2022
entrez:
15
6
2022
Statut:
ppublish
Résumé
Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was expressed in mouse dorsal horn neurons, and mice lacking NCX3 showed normal, acute pain but hypersensitivity to the second phase of the formalin test and chronic constriction injury. Dorsal horn neurons lacking NCX3 showed increased intracellular calcium following repetitive stimulation, slowed calcium clearance, and increased wind-up. Moreover, virally mediated enhanced spinal expression of NCX3 reduced central sensitization. Our study highlights Ca
Identifiants
pubmed: 35705078
pii: S0896-6273(22)00458-5
doi: 10.1016/j.neuron.2022.05.017
pmc: PMC7613464
mid: EMS152407
pii:
doi:
Substances chimiques
SLC38A3 protein, human
0
Slc8a3 protein, mouse
0
Sodium-Calcium Exchanger
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2571-2587.e13Subventions
Organisme : Wellcome Trust
ID : WT219433/Z/19/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202747/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V033638/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT107055AIA
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 102645/Z/13/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 222101/Z/20/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T020113/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 222101
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 095698Z/11/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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