d6b78a961e1f79aa136b2f1e0043df5f ant_a2022m9v11n9p1826.pdf f57918f8b65cc653de44309dfcc458e7128d3353 ant_a2022m9v11n9p1826.pdf f431ee1299356aa1e5e9c37e853493507bc67f1b21962fd2966a78dbcea507d1 ant_a2022m9v11n9p1826.pdf Title: Hydrogen-Rich Water as a Novel Therapeutic Strategy for the Affective Disorders Linked with Chronic Neuropathic Pain in Mice Subject: Neuropathic pain manifested with allodynia and hyperalgesia usually becomes a chronic condition accompanied with mood disorders. Clinical therapies for neuropathic pain are still unsatisfactory with notable side effects. Recent studies have reported the protective role of molecular hydrogen (H2) in different diseases including neurological disorders, such as Alzheimer’s as well as its antidepressant activities in animals with chronic stress. This study explored the effects of treatment with hydrogen-rich water (HRW) in male mice with neuropathic pain induced by the chronic constriction of the sciatic nerve (CCI) and the accompanying affective deficits. The likely pathways implied in the HRW analgesic activity, as well as the interaction between heme oxygenase 1 (HO-1) enzyme and H2 during neuropathic pain were also studied. The results showed: (i) the inhibitory effects of the repetitive treatment with HRW on the allodynia and hyperalgesia provoked by CCI; (ii) the anxiolytic and antidepressant actions of HRW in animals with neuropathic pain; (iii) the contribution of the antioxidant enzymes (HO-1 and NAD(P)H: quinone oxidoreductase 1) and the ATP sensitive potassium channels in the painkiller activities of HRW during neuropathic pain; (iv) a positive interaction between the HO-1 and H2 systems in inhibiting the CCI-induced neuropathy; and (v) the antioxidant, antinociceptive, anti-inflammatory and/or antiapoptotic features of HRW treatment in the dorsal root ganglia and/or amygdala of sciatic nerve-injured mice. This study demonstrates new protective actions of H2 and suggests that treatment with HRW might be an interesting therapeutic strategy for chronic neuropathic pain and its associated mood disorders. Keywords: analgesia; apoptosis; hydrogen-rich water; inflammation; molecular hydrogen;neuropathic pain; oxidative stress Author: Maria Martínez-Serrat, Ignacio Martínez-Martel, Santiago Coral-Pérez, Xue Bai, Gerard Batallé and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Sep 16 11:11:43 2022 CEST ModDate: Fri Sep 16 11:31:20 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4831570 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 AWHDWW+VnURWPalladioL Type 1 Custom yes yes no 15 0 NQCTJF+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 YKUGHU+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 ITSQKR+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 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TrueType Identity-H yes yes yes 289 0 EAJLEN+PalatinoLinotype TrueType WinAnsi yes yes no 295 0 EAJLEP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 298 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-07-01 02:41:57 CEST RepresentationInformation: ant_a2022m9v11n9p1826.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-06-30 19:53:35 CEST Size: 4831570 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 509 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Method Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Induction of Neuropathic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Mechanical Allodynia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Thermal Hyperalgesia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Cold Allodynia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Anxiety-like Behaviors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Depressive-like Behaviors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Drugs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Experimental Protocol Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Western Blot Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Children: Item: Title: Treatment with HRW Inhibited the Nociceptive Symptoms Induced by CCI Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Treatment with HRW Inhibited the Anxiety and Depressive-like Behaviors Associated with CNP Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Reversion of the Antinociceptive Effects of HRW with Specific HO-1 and NQO1 Inhibiters and a KATP Channels Blocker Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Treatment with CoPP Potentiated the Antinociceptive Effects of HRW Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: The Effects of HRW Treatment on the Expression of the Antioxidant Enzymes HO-1, SOD-1 and NQO1 in the AMG and DRG of CCI-Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: The Impact of HRW Treatment on the Expression of p-IKB, p-AKT, BAX and 4-HNE in the AMG and DRG of CCI-Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: Hydrogen-Rich Water as a Novel Therapeutic Strategy for the Affective Disorders Linked with Chronic Neuropathic Pain in Mice Author: Maria Martínez-Serrat, Ignacio Martínez-Martel, Santiago Coral-Pérez, Xue Bai, Gerard Batallé and Olga Pol Subject: Neuropathic pain manifested with allodynia and hyperalgesia usually becomes a chronic condition accompanied with mood disorders. Clinical therapies for neuropathic pain are still unsatisfactory with notable side effects. Recent studies have reported the protective role of molecular hydrogen (H2) in different diseases including neurological disorders, such as Alzheimer’s as well as its antidepressant activities in animals with chronic stress. This study explored the effects of treatment with hydrogen-rich water (HRW) in male mice with neuropathic pain induced by the chronic constriction of the sciatic nerve (CCI) and the accompanying affective deficits. The likely pathways implied in the HRW analgesic activity, as well as the interaction between heme oxygenase 1 (HO-1) enzyme and H2 during neuropathic pain were also studied. The results showed: (i) the inhibitory effects of the repetitive treatment with HRW on the allodynia and hyperalgesia provoked by CCI; (ii) the anxiolytic and antidepressant actions of HRW in animals with neuropathic pain; (iii) the contribution of the antioxidant enzymes (HO-1 and NAD(P)H: quinone oxidoreductase 1) and the ATP sensitive potassium channels in the painkiller activities of HRW during neuropathic pain; (iv) a positive interaction between the HO-1 and H2 systems in inhibiting the CCI-induced neuropathy; and (v) the antioxidant, antinociceptive, anti-inflammatory and/or antiapoptotic features of HRW treatment in the dorsal root ganglia and/or amygdala of sciatic nerve-injured mice. This study demonstrates new protective actions of H2 and suggests that treatment with HRW might be an interesting therapeutic strategy for chronic neuropathic pain and its associated mood disorders. 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