Universidad Peruana Cayetano Heredia

Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms

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dc.contributor.author Trendafilova, Teodora
dc.contributor.author Adhikari, Kaustubh
dc.contributor.author Schmid, Annina B.
dc.contributor.author Patel, Ryan
dc.contributor.author Polgar, Erika
dc.contributor.author Chisholm, Kim I.
dc.contributor.author Middleton, Steven J.
dc.contributor.author Boyle, Kieran
dc.contributor.author Dickie, Allen C.
dc.contributor.author Semizoglou, Evangelia
dc.contributor.author Perez-Sanchez, Jimena
dc.contributor.author Bell, Andrew M.
dc.contributor.author Ramirez-Aristeguieta, Luis Miguel
dc.contributor.author Khoury, Samar
dc.contributor.author Ivanov, Aleksandar
dc.contributor.author Wildner, Hendrik
dc.contributor.author Ferris, Eleanor
dc.contributor.author Chacon-Duque, Juan-Camilo
dc.contributor.author Sokolow, Sophie
dc.contributor.author Saad Boghdady, Mohamed A.
dc.contributor.author Herchuelz, Andre
dc.contributor.author Faux, Pierre
dc.contributor.author Poletti, Giovanni
dc.contributor.author Gallo López-Aliaga, Carla Maria
dc.contributor.author Rothhammer, Francisco
dc.contributor.author Bedoya, Gabriel
dc.contributor.author Zeilhofer, Hanns Ulrich
dc.contributor.author Diatchenko, Luda
dc.contributor.author McMahon, Stephen B.
dc.contributor.author Todd, Andrew J.
dc.contributor.author Dickenson, Anthony H.
dc.contributor.author Ruiz-Linares, Andres
dc.contributor.author Bennett, David L.
dc.date.accessioned 2022-09-09T18:52:23Z
dc.date.available 2022-09-09T18:52:23Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12166
dc.description.abstract 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 Ca2+ efflux as a pathway underlying temporal summation and persistent pain, which may be amenable to therapeutic targeting. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries Neuron
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject wind-up en_US
dc.subject central sensitization en_US
dc.subject temporal summation en_US
dc.subject GWAS en_US
dc.subject pain en_US
dc.subject spinal cord en_US
dc.subject in vivo electrophysiology en_US
dc.subject in vivo calcium imaging en_US
dc.title Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.neuron.2022.05.017
dc.relation.issn 1097-4199


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