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Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats

Persistent pain affecting patients with inflammatory bowel diseases (IBDs) is still very difficult to treat. Carbonic anhydrase (CA) represents an intriguing pharmacological target considering the anti-hyperalgesic efficacy displayed by CA inhibitors in both inflammatory and neuropathic pain models....

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Autores principales: Lucarini, Elena, Nocentini, Alessio, Bonardi, Alessandro, Chiaramonte, Niccolò, Parisio, Carmen, Micheli, Laura, Toti, Alessandra, Ferrara, Valentina, Carrino, Donatello, Pacini, Alessandra, Romanelli, Maria Novella, Supuran, Claudiu T., Ghelardini, Carla, Di Cesare Mannelli, Lorenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533707/
https://www.ncbi.nlm.nih.gov/pubmed/34685520
http://dx.doi.org/10.3390/cells10102540
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author Lucarini, Elena
Nocentini, Alessio
Bonardi, Alessandro
Chiaramonte, Niccolò
Parisio, Carmen
Micheli, Laura
Toti, Alessandra
Ferrara, Valentina
Carrino, Donatello
Pacini, Alessandra
Romanelli, Maria Novella
Supuran, Claudiu T.
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
author_facet Lucarini, Elena
Nocentini, Alessio
Bonardi, Alessandro
Chiaramonte, Niccolò
Parisio, Carmen
Micheli, Laura
Toti, Alessandra
Ferrara, Valentina
Carrino, Donatello
Pacini, Alessandra
Romanelli, Maria Novella
Supuran, Claudiu T.
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
author_sort Lucarini, Elena
collection PubMed
description Persistent pain affecting patients with inflammatory bowel diseases (IBDs) is still very difficult to treat. Carbonic anhydrase (CA) represents an intriguing pharmacological target considering the anti-hyperalgesic efficacy displayed by CA inhibitors in both inflammatory and neuropathic pain models. The aim of this work was to evaluate the effect of inhibiting CA IV, particularly when expressed in the gut, on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) in rats. Visceral sensitivity was assessed by measuring animals’ abdominal responses to colorectal distension. Repeated treatment with the selective CA IV inhibitors AB-118 and NIK-67 effectively counteracted the development of visceral pain induced by DNBS. In addition to pain relief, AB-118 showed a protective effect against colon damage. By contrast, the anti-hyperalgesic activity of NIK-67 was independent of colon healing, suggesting a direct protective effect of NIK-67 on visceral sensitivity. The enzymatic activity and the expression of CA IV resulted significantly increased after DNBS injection. NIK-67 normalised CA IV activity in DNBS animals, while AB-118 was partially effective. None of these compounds influenced CA IV expression through the colon. Although further investigations are needed to study the underlying mechanisms, CA IV inhibitors are promising candidates in the search for therapies to relieve visceral pain in IBDs.
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spelling pubmed-85337072021-10-23 Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats Lucarini, Elena Nocentini, Alessio Bonardi, Alessandro Chiaramonte, Niccolò Parisio, Carmen Micheli, Laura Toti, Alessandra Ferrara, Valentina Carrino, Donatello Pacini, Alessandra Romanelli, Maria Novella Supuran, Claudiu T. Ghelardini, Carla Di Cesare Mannelli, Lorenzo Cells Article Persistent pain affecting patients with inflammatory bowel diseases (IBDs) is still very difficult to treat. Carbonic anhydrase (CA) represents an intriguing pharmacological target considering the anti-hyperalgesic efficacy displayed by CA inhibitors in both inflammatory and neuropathic pain models. The aim of this work was to evaluate the effect of inhibiting CA IV, particularly when expressed in the gut, on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) in rats. Visceral sensitivity was assessed by measuring animals’ abdominal responses to colorectal distension. Repeated treatment with the selective CA IV inhibitors AB-118 and NIK-67 effectively counteracted the development of visceral pain induced by DNBS. In addition to pain relief, AB-118 showed a protective effect against colon damage. By contrast, the anti-hyperalgesic activity of NIK-67 was independent of colon healing, suggesting a direct protective effect of NIK-67 on visceral sensitivity. The enzymatic activity and the expression of CA IV resulted significantly increased after DNBS injection. NIK-67 normalised CA IV activity in DNBS animals, while AB-118 was partially effective. None of these compounds influenced CA IV expression through the colon. Although further investigations are needed to study the underlying mechanisms, CA IV inhibitors are promising candidates in the search for therapies to relieve visceral pain in IBDs. MDPI 2021-09-26 /pmc/articles/PMC8533707/ /pubmed/34685520 http://dx.doi.org/10.3390/cells10102540 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lucarini, Elena
Nocentini, Alessio
Bonardi, Alessandro
Chiaramonte, Niccolò
Parisio, Carmen
Micheli, Laura
Toti, Alessandra
Ferrara, Valentina
Carrino, Donatello
Pacini, Alessandra
Romanelli, Maria Novella
Supuran, Claudiu T.
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats
title Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats
title_full Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats
title_fullStr Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats
title_full_unstemmed Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats
title_short Carbonic Anhydrase IV Selective Inhibitors Counteract the Development of Colitis-Associated Visceral Pain in Rats
title_sort carbonic anhydrase iv selective inhibitors counteract the development of colitis-associated visceral pain in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533707/
https://www.ncbi.nlm.nih.gov/pubmed/34685520
http://dx.doi.org/10.3390/cells10102540
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