Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model

Abstract: Background: Hindpaw injection of formalin in rodents is used to assess acute persistent pain. The response to formalin is biphasic. The initial response (first minutes) is thought to be linked to inflammatory, peripheral mechanisms, while the latter (around 30 min after the injection),...

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Autores principales: Gobetto, María Natalia, Salinas Castellanos, Libia Catalina, Contreras, Natalia Estefanía, Sodero, Alejandro Omar, Cambiagno, Damián Alejandro, Mingolo Malnati, Georgina Oriana, Montes, Mayra Micaela, Uchitel, Osvaldo Daniel, Weissmann, Carina
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Lenguaje:Inglés
Publicado: Multidisciplinary Digital Publishing Institute 2023
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Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/16062
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spelling I33-R139-123456789-160622023-11-23T17:43:17Z Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model Gobetto, María Natalia Salinas Castellanos, Libia Catalina Contreras, Natalia Estefanía Sodero, Alejandro Omar Cambiagno, Damián Alejandro Mingolo Malnati, Georgina Oriana Montes, Mayra Micaela Uchitel, Osvaldo Daniel Weissmann, Carina CANALES ASIC1 miIR485-5p miARN DOLOR FORMALINA RATON Abstract: Background: Hindpaw injection of formalin in rodents is used to assess acute persistent pain. The response to formalin is biphasic. The initial response (first minutes) is thought to be linked to inflammatory, peripheral mechanisms, while the latter (around 30 min after the injection), is linked to central mechanisms. This model is useful to analyze the effect of drugs at one or both phases, and the involvement of ion channels in the response. Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in pain conditions. Recently, psalmotoxin-1 (Pctx-1), a toxin that inhibits ASIC1a-constituted channels, and antisense ASIC1a-RNA, intrathecal administered in mice were shown to affect both phases of the test. Methods: The mouse formalin test was performed on C57/BL6 7- to 9-week-old mice. Behavioral tests were conducted and tissue was extracted to detect proteins (ASIC1 and pERK) and ASIC1-mRNA and mir485-5p levels. Results: The injection of formalin was accompanied by an increase in ASIC1 levels. This was detected at the contralateral anterior cingulate cortex (ACC) compared to the ipsilateral side, and both sides of the ACC of vehicle-injected animals. At the spinal cord and dorsal root ganglia, ASIC1 levels followed a gradient stronger at lumbar (L) 3 and decreased towards L5. Gender differences were detected at the ACC; with female mice showing higher ASIC1a levels at the ACC. No significant changes in ASIC1-mRNA levels were detected. Evidence suggests ASIC1 upregulation depends on regulatory microRNAs. Conclusion: This work highlights the important role of ASIC1 in pain and the potential role of pharmacological therapies aimed at this channel. 2023-03-23T11:45:51Z 2023-03-23T11:45:51Z 2022 Artículo Gobetto, M. N. Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model [en línea]. Pharmaceuticals. 2022, 15 (12). doi:10.3390/ph15121539. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/16062 1424-8247 https://repositorio.uca.edu.ar/handle/123456789/16062 10.3390/ph15121539 36558990 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Multidisciplinary Digital Publishing Institute Pharmaceuticals Vol.15, No.12, 2022
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CANALES ASIC1
miIR485-5p
miARN
DOLOR
FORMALINA
RATON
spellingShingle CANALES ASIC1
miIR485-5p
miARN
DOLOR
FORMALINA
RATON
Gobetto, María Natalia
Salinas Castellanos, Libia Catalina
Contreras, Natalia Estefanía
Sodero, Alejandro Omar
Cambiagno, Damián Alejandro
Mingolo Malnati, Georgina Oriana
Montes, Mayra Micaela
Uchitel, Osvaldo Daniel
Weissmann, Carina
Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model
topic_facet CANALES ASIC1
miIR485-5p
miARN
DOLOR
FORMALINA
RATON
description Abstract: Background: Hindpaw injection of formalin in rodents is used to assess acute persistent pain. The response to formalin is biphasic. The initial response (first minutes) is thought to be linked to inflammatory, peripheral mechanisms, while the latter (around 30 min after the injection), is linked to central mechanisms. This model is useful to analyze the effect of drugs at one or both phases, and the involvement of ion channels in the response. Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in pain conditions. Recently, psalmotoxin-1 (Pctx-1), a toxin that inhibits ASIC1a-constituted channels, and antisense ASIC1a-RNA, intrathecal administered in mice were shown to affect both phases of the test. Methods: The mouse formalin test was performed on C57/BL6 7- to 9-week-old mice. Behavioral tests were conducted and tissue was extracted to detect proteins (ASIC1 and pERK) and ASIC1-mRNA and mir485-5p levels. Results: The injection of formalin was accompanied by an increase in ASIC1 levels. This was detected at the contralateral anterior cingulate cortex (ACC) compared to the ipsilateral side, and both sides of the ACC of vehicle-injected animals. At the spinal cord and dorsal root ganglia, ASIC1 levels followed a gradient stronger at lumbar (L) 3 and decreased towards L5. Gender differences were detected at the ACC; with female mice showing higher ASIC1a levels at the ACC. No significant changes in ASIC1-mRNA levels were detected. Evidence suggests ASIC1 upregulation depends on regulatory microRNAs. Conclusion: This work highlights the important role of ASIC1 in pain and the potential role of pharmacological therapies aimed at this channel.
format Artículo
author Gobetto, María Natalia
Salinas Castellanos, Libia Catalina
Contreras, Natalia Estefanía
Sodero, Alejandro Omar
Cambiagno, Damián Alejandro
Mingolo Malnati, Georgina Oriana
Montes, Mayra Micaela
Uchitel, Osvaldo Daniel
Weissmann, Carina
author_facet Gobetto, María Natalia
Salinas Castellanos, Libia Catalina
Contreras, Natalia Estefanía
Sodero, Alejandro Omar
Cambiagno, Damián Alejandro
Mingolo Malnati, Georgina Oriana
Montes, Mayra Micaela
Uchitel, Osvaldo Daniel
Weissmann, Carina
author_sort Gobetto, María Natalia
title Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model
title_short Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model
title_full Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model
title_fullStr Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model
title_full_unstemmed Segmental upregulation of ASIC1 channels in the formalin acute pain mouse model
title_sort segmental upregulation of asic1 channels in the formalin acute pain mouse model
publisher Multidisciplinary Digital Publishing Institute
publishDate 2023
url https://repositorio.uca.edu.ar/handle/123456789/16062
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