db5a10d5e3e65090c013018254ecbdc4 265123.pdf 9744b3fd86b2c8e58edd55b25859dd806db309d4 265123.pdf 7c44d6005cb2545dd5e7387bdf883e912f9ac9e536aba5ef77d2b609d5129b5c 265123.pdf Title: Hydrogen Sulfide Increases the Analgesic Effects of - and -Opioid Receptors during Neuropathic Pain: Pathways Implicated Subject: Recent studies have revealed that hydrogen sulfide (H2S) increases the analgesic actions of the -opioid receptor (DOR) in inflammatory pain. However, the possible improvement of the analgesia of -opioid receptor (MOR) and DOR agonists during neuropathic pain, through pretreatment with two slow-releasing H2S donors—DADS (diallyl disulfide) and GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex)—is still unknown. In male C57BL/6J mice with neuropathic pain incited by chronic constriction of the sciatic nerve (CCI), we evaluated: (1) the influence of DADS (3.5 mg/kg) and GYY4137 (0.7 mg/kg) on the inhibition of the allodynia and hyperalgesia produced by the systemic or local administration of morphine (3 mg/kg or 65 g) and UFP-512 (1 mg/kg or 12.5 g); (2) the reversion of the antinociceptive actions of high doses of DADS (30 mg/kg) and GYY4137 (24 mg/kg) with MOR and DOR antagonists; and (3) the effects of H2S donors on oxidative stress, apoptotic responses, and MOR and DOR expression in the medial septum (MS) and dorsal root ganglia (DRG). The results revealed that both DADS and GYY4137 improved the antiallodynic effects of morphine and UFP-512, possibly by up-regulating MOR and DOR expression in DRG. The administration of MOR and DOR antagonists blocked the analgesic properties of DADS and GYY4137, revealing the feasible participation of the endogenous opioid system in H2S analgesic effects. Moreover, both H2S donors inhibited oxidative stress and apoptosis generated by CCI in the MS and/or DRG. This study suggests the co-treatment of H2S donors with MOR or DOR agonists as a potential therapy for neuropathic pain. Keywords: analgesia; apoptosis; hydrogen sulfide; neuropathic pain; opioids; oxidative stress Author: Xue Bai, Gerard Batallé, Gianfranco Balboni and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jul 7 04:04:36 2022 CEST ModDate: Thu Jul 7 04:08:31 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5281654 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DFGUHK+EURB10 Type 1 Builtin yes yes no 10 0 BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 14 0 PHEGVP+VnURWPalladioL Type 1 Custom yes yes no 19 0 UOSAVX+EURM10 Type 1 Builtin yes yes no 23 0 DBCCZR+URWPalladioL-Bold Type 1 Custom yes yes no 27 0 HTIIVC+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 YPMULZ+URWPalladioL-Ital Type 1 Custom yes yes no 36 0 QJTLUA+EURM7 Type 1 Builtin yes yes no 40 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 58 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 80 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-06-17 02:32:10 CEST RepresentationInformation: 265123.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-06-16 12:17:41 CEST Size: 5281654 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 411 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: Western Blot Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Experimental Procedures 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: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: The Effects of the Co-Administration of DADS or GYY4137 with Morphine or UFP-512 on the Allodynia and Hyperalgesia Caused by Nerve Injury Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Reversal of the Antinociceptive Effects of DADS and GYY4137 with MOR and DOR Antagonists Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Effects of DADS and GYY4137 on the Expression of Antioxidant Enzymes in the MS and DRG of Nerve-Injured Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Effects of Treatment with DADS and GYY4137 on the Protein Levels of 4-HNE and BAX in the MS and DRG of Nerve-Injured Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Actions of DADS and GYY4137 Treatments on the Protein Levels of MOR and DOR in the MS and DRG of Nerve-Injured Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Discussions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Info: Title: Hydrogen Sulfide Increases the Analgesic Effects of - and -Opioid Receptors during Neuropathic Pain: Pathways Implicated Author: Xue Bai, Gerard Batallé, Gianfranco Balboni and Olga Pol Subject: Recent studies have revealed that hydrogen sulfide (H2S) increases the analgesic actions of the -opioid receptor (DOR) in inflammatory pain. However, the possible improvement of the analgesia of -opioid receptor (MOR) and DOR agonists during neuropathic pain, through pretreatment with two slow-releasing H2S donors DADS (diallyl disulfide) and GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex) is still unknown. In male C57BL/6J mice with neuropathic pain incited by chronic constriction of the sciatic nerve (CCI), we evaluated: (1) the influence of DADS (3.5 mg/kg) and GYY4137 (0.7 mg/kg) on the inhibition of the allodynia and hyperalgesia produced by the systemic or local administration of morphine (3 mg/kg or 65 g) and UFP-512 (1 mg/kg or 12.5 g); (2) the reversion of the antinociceptive actions of high doses of DADS (30 mg/kg) and GYY4137 (24 mg/kg) with MOR and DOR antagonists; and (3) the effects of H2S donors on oxidative stress, apoptotic responses, and MOR and DOR expression in the medial septum (MS) and dorsal root ganglia (DRG). The results revealed that both DADS and GYY4137 improved the antiallodynic effects of morphine and UFP-512, possibly by up-regulating MOR and DOR expression in DRG. The administration of MOR and DOR antagonists blocked the analgesic properties of DADS and GYY4137, revealing the feasible participation of the endogenous opioid system in H2S analgesic effects. Moreover, both H2S donors inhibited oxidative stress and apoptosis generated by CCI in the MS and/or DRG. This study suggests the co-treatment of H2S donors with MOR or DOR agonists as a potential therapy for neuropathic pain. 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