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The neuronal potassium current I(A) is a potential target for pain during chronic inflammation
Voltage‐gated ion channels play a key role in the action potential (AP) initiation and its propagation in sensory neurons. Modulation of their activity during chronic inflammation creates a persistent pain state. In this study, we sought to determine how peripheral inflammation caused by complete Fr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371350/ https://www.ncbi.nlm.nih.gov/pubmed/34405579 http://dx.doi.org/10.14814/phy2.14975 |
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author | Biet, Michael Dansereau, Marc‐André Sarret, Philippe Dumaine, Robert |
author_facet | Biet, Michael Dansereau, Marc‐André Sarret, Philippe Dumaine, Robert |
author_sort | Biet, Michael |
collection | PubMed |
description | Voltage‐gated ion channels play a key role in the action potential (AP) initiation and its propagation in sensory neurons. Modulation of their activity during chronic inflammation creates a persistent pain state. In this study, we sought to determine how peripheral inflammation caused by complete Freund's adjuvant (CFA) alters the fast sodium (I(Na)), L‐type calcium (I(CaL)), and potassium (I(K)) currents in primary afferent fibers to increase nociception. In our model, intraplantar administration of CFA induced mechanical allodynia and thermal hyperalgesia at day 14 post‐injection. Using whole‐cell patch‐clamp recording in dissociated small (C), medium (Aδ), and large‐sized (Aβ) rat dorsal root ganglion (DRG) neurons, we found that CFA prolonged the AP duration and increased the amplitude of the tetrodotoxin‐resistant (TTX‐r) I(Na) in Aβ fibers. In addition, CFA accelerated the recovery of I(Na) from inactivation in C and Aδ nociceptive fibers but enhanced the late sodium current (I(NaL)) only in Aδ and Aβ neurons. Inflammation similarly reduced the amplitude of I(CaL) in each neuronal cell type. Fourteen days after injection, CFA reduced both components of I(K) (I(Kdr) and I(A)) in Aδ fibers. We also found that I(A) was significantly larger in C and Aδ neurons in normal conditions and during chronic inflammation. Our data, therefore, suggest that targeting the transient potassium current I(A) represents an efficient way to shift the balance toward antinociception during inflammation, since its activation will selectively decrease the AP duration in nociceptive fibers. Altogether, our data indicate that complex interactions between I(K), I(Na), and I(CaL) reduce pain threshold by concomitantly enhancing the activity of nociceptive neurons and reducing the inhibitory action of Aβ fibers during chronic inflammation. |
format | Online Article Text |
id | pubmed-8371350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83713502021-08-23 The neuronal potassium current I(A) is a potential target for pain during chronic inflammation Biet, Michael Dansereau, Marc‐André Sarret, Philippe Dumaine, Robert Physiol Rep Original Articles Voltage‐gated ion channels play a key role in the action potential (AP) initiation and its propagation in sensory neurons. Modulation of their activity during chronic inflammation creates a persistent pain state. In this study, we sought to determine how peripheral inflammation caused by complete Freund's adjuvant (CFA) alters the fast sodium (I(Na)), L‐type calcium (I(CaL)), and potassium (I(K)) currents in primary afferent fibers to increase nociception. In our model, intraplantar administration of CFA induced mechanical allodynia and thermal hyperalgesia at day 14 post‐injection. Using whole‐cell patch‐clamp recording in dissociated small (C), medium (Aδ), and large‐sized (Aβ) rat dorsal root ganglion (DRG) neurons, we found that CFA prolonged the AP duration and increased the amplitude of the tetrodotoxin‐resistant (TTX‐r) I(Na) in Aβ fibers. In addition, CFA accelerated the recovery of I(Na) from inactivation in C and Aδ nociceptive fibers but enhanced the late sodium current (I(NaL)) only in Aδ and Aβ neurons. Inflammation similarly reduced the amplitude of I(CaL) in each neuronal cell type. Fourteen days after injection, CFA reduced both components of I(K) (I(Kdr) and I(A)) in Aδ fibers. We also found that I(A) was significantly larger in C and Aδ neurons in normal conditions and during chronic inflammation. Our data, therefore, suggest that targeting the transient potassium current I(A) represents an efficient way to shift the balance toward antinociception during inflammation, since its activation will selectively decrease the AP duration in nociceptive fibers. Altogether, our data indicate that complex interactions between I(K), I(Na), and I(CaL) reduce pain threshold by concomitantly enhancing the activity of nociceptive neurons and reducing the inhibitory action of Aβ fibers during chronic inflammation. John Wiley and Sons Inc. 2021-08-17 /pmc/articles/PMC8371350/ /pubmed/34405579 http://dx.doi.org/10.14814/phy2.14975 Text en © 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Biet, Michael Dansereau, Marc‐André Sarret, Philippe Dumaine, Robert The neuronal potassium current I(A) is a potential target for pain during chronic inflammation |
title | The neuronal potassium current I(A) is a potential target for pain during chronic inflammation |
title_full | The neuronal potassium current I(A) is a potential target for pain during chronic inflammation |
title_fullStr | The neuronal potassium current I(A) is a potential target for pain during chronic inflammation |
title_full_unstemmed | The neuronal potassium current I(A) is a potential target for pain during chronic inflammation |
title_short | The neuronal potassium current I(A) is a potential target for pain during chronic inflammation |
title_sort | neuronal potassium current i(a) is a potential target for pain during chronic inflammation |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371350/ https://www.ncbi.nlm.nih.gov/pubmed/34405579 http://dx.doi.org/10.14814/phy2.14975 |
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