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Sodium-calcium exch...
Sodium-calcium exchanger-3 regulates pain “wind-up” : From human psychophysics to spinal mechanisms
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Trendafilova, Teodora (author)
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Adhikari, Kaustubh (author)
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Schmid, Annina B. (author)
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Patel, Ryan (author)
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Polgár, Erika (author)
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Chisholm, Kim I. (author)
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Middleton, Steven J. (author)
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Boyle, Kieran (author)
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Dickie, Allen C. (author)
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Semizoglou, Evangelia (author)
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Perez-Sanchez, Jimena (author)
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Bell, Andrew M. (author)
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Ramirez-Aristeguieta, Luis Miguel (author)
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Khoury, Samar (author)
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Ivanov, Aleksandar (author)
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Wildner, Hendrik (author)
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Ferris, Eleanor (author)
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- Chacón-Duque, Juan-Camilo (author)
- Stockholms universitet,Institutionen för arkeologi och antikens kultur,University College London, UK
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Sokolow, Sophie (author)
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Saad Boghdady, Mohamed A. (author)
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Herchuelz, André (author)
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Faux, Pierre (author)
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Poletti, Giovanni (author)
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Gallo, Carla (author)
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Rothhammer, Francisco (author)
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Bedoya, Gabriel (author)
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Zeilhofer, Hanns Ulrich (author)
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Diatchenko, Luda (author)
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McMahon, Stephen B. (author)
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Todd, Andrew J. (author)
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Dickenson, Anthony H. (author)
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Ruiz-Linares, Andres (author)
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Bennett, David L. (author)
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 110:16, s. 2571-2587.e13
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- central sensitization
- GWAS
- in vivo calcium imaging
- in vivo electrophysiology
- pain
- spinal cord
- temporal summation
- wind-up
- calcium
- sodium calcium exchange protein
- animal
- genetics
- human
- mouse
- posterior horn cell
- psychophysics
- Animals
- Humans
- Mice
- Posterior Horn Cells
- Sodium-Calcium Exchanger
Publication and Content Type
- ref (subject category)
- art (subject category)
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Neuron
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To the university's database
- By the author/editor
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Trendafilova, Te ...
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Adhikari, Kaustu ...
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Schmid, Annina B ...
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Patel, Ryan
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Polgár, Erika
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Chisholm, Kim I.
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show more...
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Middleton, Steve ...
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Boyle, Kieran
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Dickie, Allen C.
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Semizoglou, Evan ...
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Perez-Sanchez, J ...
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Bell, Andrew M.
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Ramirez-Aristegu ...
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Khoury, Samar
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Ivanov, Aleksand ...
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Wildner, Hendrik
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Ferris, Eleanor
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Chacón-Duque, Ju ...
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Sokolow, Sophie
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Saad Boghdady, M ...
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Herchuelz, André
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Faux, Pierre
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Poletti, Giovann ...
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Gallo, Carla
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Rothhammer, Fran ...
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Bedoya, Gabriel
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Zeilhofer, Hanns ...
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Diatchenko, Luda
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McMahon, Stephen ...
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Todd, Andrew J.
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Dickenson, Antho ...
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Ruiz-Linares, An ...
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Bennett, David L ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Neuron
- By the university
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Stockholm University