Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice

Chronic inflammatory pain is manifested in many diseases. The potential use of molecular hydrogen (H<sub>2</sub>) as a new therapy for neurological disorders has been demonstrated. Recent studies prove its analgesic properties in animals with neuropathic pain, but the possible antinocice...

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Main Authors: Santiago Coral-Pérez, Ignacio Martínez-Martel, Maria Martínez-Serrat, Gerard Batallé, Xue Bai, Christie R. A. Leite-Panissi, Olga Pol
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/11/2153
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author Santiago Coral-Pérez
Ignacio Martínez-Martel
Maria Martínez-Serrat
Gerard Batallé
Xue Bai
Christie R. A. Leite-Panissi
Olga Pol
author_facet Santiago Coral-Pérez
Ignacio Martínez-Martel
Maria Martínez-Serrat
Gerard Batallé
Xue Bai
Christie R. A. Leite-Panissi
Olga Pol
author_sort Santiago Coral-Pérez
collection DOAJ
description Chronic inflammatory pain is manifested in many diseases. The potential use of molecular hydrogen (H<sub>2</sub>) as a new therapy for neurological disorders has been demonstrated. Recent studies prove its analgesic properties in animals with neuropathic pain, but the possible antinociceptive, antidepressant, and/or anxiolytic actions of H<sub>2</sub> during persistent inflammatory pain have not been investigated. Therefore, using male mice with chronic inflammatory pain incited by the subplantar injection of complete Freud’s adjuvant (CFA), we assessed the actions of hydrogen-rich water (HRW) systemically administered on: (1) the nociceptive responses and affective disorders associated and (2) the oxidative (4-hydroxy-2-nonenal; 4-HNE), inflammatory (phosphorylated-NF-kB inhibitor alpha; p-IKBα), and apoptotic (Bcl-2-like protein 4; BAX) changes provoked by CFA in the paws and amygdala. The role of the antioxidant system in the analgesia induced by HRW systemically and locally administered was also determined. Our results revealed that the intraperitoneal administration of HRW, besides reducing inflammatory pain, also inhibited the depressive- and anxiolytic-like behaviors associated and the over expression of 4-HNE, p-IKBα, and BAX in paws and amygdala. The contribution of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1 pathway in the analgesic activities of HRW, systemically or locally administered, was also shown. These data revealed the analgesic, antidepressant, and anxiolytic actions of HRW. The protective, anti-inflammatory, and antioxidant qualities of this treatment during inflammatory pain were also demonstrated. Therefore, this study proposes the usage of HRW as a potential therapy for chronic inflammatory pain and linked comorbidities.
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spelling doaj.art-af5407d49c504a87b25ea3b2365382022023-11-24T03:30:04ZengMDPI AGAntioxidants2076-39212022-10-011111215310.3390/antiox11112153Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in MiceSantiago Coral-Pérez0Ignacio Martínez-Martel1Maria Martínez-Serrat2Gerard Batallé3Xue Bai4Christie R. A. Leite-Panissi5Olga Pol6Grup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, SpainGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, SpainGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, SpainGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, SpainGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, SpainDepartment of Psychology, Faculty of Philosophy Science and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040-901, SP, BrazilGrup de Neurofarmacologia Molecular, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, SpainChronic inflammatory pain is manifested in many diseases. The potential use of molecular hydrogen (H<sub>2</sub>) as a new therapy for neurological disorders has been demonstrated. Recent studies prove its analgesic properties in animals with neuropathic pain, but the possible antinociceptive, antidepressant, and/or anxiolytic actions of H<sub>2</sub> during persistent inflammatory pain have not been investigated. Therefore, using male mice with chronic inflammatory pain incited by the subplantar injection of complete Freud’s adjuvant (CFA), we assessed the actions of hydrogen-rich water (HRW) systemically administered on: (1) the nociceptive responses and affective disorders associated and (2) the oxidative (4-hydroxy-2-nonenal; 4-HNE), inflammatory (phosphorylated-NF-kB inhibitor alpha; p-IKBα), and apoptotic (Bcl-2-like protein 4; BAX) changes provoked by CFA in the paws and amygdala. The role of the antioxidant system in the analgesia induced by HRW systemically and locally administered was also determined. Our results revealed that the intraperitoneal administration of HRW, besides reducing inflammatory pain, also inhibited the depressive- and anxiolytic-like behaviors associated and the over expression of 4-HNE, p-IKBα, and BAX in paws and amygdala. The contribution of the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 and NAD(P)H: quinone oxidoreductase 1 pathway in the analgesic activities of HRW, systemically or locally administered, was also shown. These data revealed the analgesic, antidepressant, and anxiolytic actions of HRW. The protective, anti-inflammatory, and antioxidant qualities of this treatment during inflammatory pain were also demonstrated. Therefore, this study proposes the usage of HRW as a potential therapy for chronic inflammatory pain and linked comorbidities.https://www.mdpi.com/2076-3921/11/11/2153allodyniaanxietyapoptosisdepressionhyperalgesiainflammatory pain
spellingShingle Santiago Coral-Pérez
Ignacio Martínez-Martel
Maria Martínez-Serrat
Gerard Batallé
Xue Bai
Christie R. A. Leite-Panissi
Olga Pol
Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice
Antioxidants
allodynia
anxiety
apoptosis
depression
hyperalgesia
inflammatory pain
title Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice
title_full Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice
title_fullStr Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice
title_full_unstemmed Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice
title_short Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice
title_sort treatment with hydrogen rich water improves the nociceptive and anxio depressive like behaviors associated with chronic inflammatory pain in mice
topic allodynia
anxiety
apoptosis
depression
hyperalgesia
inflammatory pain
url https://www.mdpi.com/2076-3921/11/11/2153
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