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Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice

Oxaliplatin is a key drug for colorectal cancer that causes OXP-induced peripheral neuropathy, a dose-limiting effect characterized by cold and tactile hyperesthesia. The relationship between the sensory nervous system and modulation of the renin-angiotensin system has been described, focusing on pa...

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Autores principales: Bouchenaki, Hichem, Danigo, Aurore, Bernard, Amandine, Bessaguet, Flavien, Richard, Laurence, Sturtz, Franck, Balayssac, David, Magy, Laurent, Demiot, Claire
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326755/
https://www.ncbi.nlm.nih.gov/pubmed/34349658
http://dx.doi.org/10.3389/fphar.2021.712442
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author Bouchenaki, Hichem
Danigo, Aurore
Bernard, Amandine
Bessaguet, Flavien
Richard, Laurence
Sturtz, Franck
Balayssac, David
Magy, Laurent
Demiot, Claire
author_facet Bouchenaki, Hichem
Danigo, Aurore
Bernard, Amandine
Bessaguet, Flavien
Richard, Laurence
Sturtz, Franck
Balayssac, David
Magy, Laurent
Demiot, Claire
author_sort Bouchenaki, Hichem
collection PubMed
description Oxaliplatin is a key drug for colorectal cancer that causes OXP-induced peripheral neuropathy, a dose-limiting effect characterized by cold and tactile hyperesthesia. The relationship between the sensory nervous system and modulation of the renin-angiotensin system has been described, focusing on pain and neurodegeneration in several animal models. We assessed the effect of the RAS modulator, ramipril, an angiotensin converting-enzyme inhibitor in a mouse model of OXP-induced acute pain syndrome. OXP was administered in Swiss mice at a cumulative dose of 15 mg/kg (3 x 5 mg/kg/3 days, i.p.). RAM was administered i.p. every day from 24 h before the first OXP injection until the end of the experiments. We evaluated OIAS development and treatment effects by sensorimotor tests, intraepidermal nerve fiber and dorsal root ganglia-neuron immunohistochemical analyses, and sciatic nerve ultrastructural analysis. OXP-treated mice showed tactile allodynia and cold hypersensitivity, without motor impairment and evidence of nerve degeneration. RAM prevented cold sensitivity and improved recovery of normal tactile sensitivity in OXP-treated mice. Our finding that RAM alleviates OXP-induced pain is a step towards evaluating its therapeutic potential in patients receiving OXP treatment.
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spelling pubmed-83267552021-08-03 Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice Bouchenaki, Hichem Danigo, Aurore Bernard, Amandine Bessaguet, Flavien Richard, Laurence Sturtz, Franck Balayssac, David Magy, Laurent Demiot, Claire Front Pharmacol Pharmacology Oxaliplatin is a key drug for colorectal cancer that causes OXP-induced peripheral neuropathy, a dose-limiting effect characterized by cold and tactile hyperesthesia. The relationship between the sensory nervous system and modulation of the renin-angiotensin system has been described, focusing on pain and neurodegeneration in several animal models. We assessed the effect of the RAS modulator, ramipril, an angiotensin converting-enzyme inhibitor in a mouse model of OXP-induced acute pain syndrome. OXP was administered in Swiss mice at a cumulative dose of 15 mg/kg (3 x 5 mg/kg/3 days, i.p.). RAM was administered i.p. every day from 24 h before the first OXP injection until the end of the experiments. We evaluated OIAS development and treatment effects by sensorimotor tests, intraepidermal nerve fiber and dorsal root ganglia-neuron immunohistochemical analyses, and sciatic nerve ultrastructural analysis. OXP-treated mice showed tactile allodynia and cold hypersensitivity, without motor impairment and evidence of nerve degeneration. RAM prevented cold sensitivity and improved recovery of normal tactile sensitivity in OXP-treated mice. Our finding that RAM alleviates OXP-induced pain is a step towards evaluating its therapeutic potential in patients receiving OXP treatment. Frontiers Media S.A. 2021-07-19 /pmc/articles/PMC8326755/ /pubmed/34349658 http://dx.doi.org/10.3389/fphar.2021.712442 Text en Copyright © 2021 Bouchenaki, Danigo, Bernard, Bessaguet, Richard, Sturtz, Balayssac, Magy and Demiot. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Bouchenaki, Hichem
Danigo, Aurore
Bernard, Amandine
Bessaguet, Flavien
Richard, Laurence
Sturtz, Franck
Balayssac, David
Magy, Laurent
Demiot, Claire
Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice
title Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice
title_full Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice
title_fullStr Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice
title_full_unstemmed Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice
title_short Ramipril Alleviates Oxaliplatin-Induced Acute Pain Syndrome in Mice
title_sort ramipril alleviates oxaliplatin-induced acute pain syndrome in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326755/
https://www.ncbi.nlm.nih.gov/pubmed/34349658
http://dx.doi.org/10.3389/fphar.2021.712442
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