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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....
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8533707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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