f0102c420eb6280767d79798bf7a7169 pmc_34943080.pdf 0ae1265cb9283be5390ff9669580c83d1850c852 pmc_34943080.pdf f9946b9478f1ee069e39297c5293ee24d7a41339805ffb571314c86bed5f202d pmc_34943080.pdf Title: Hydrogen Sulfide Inhibits Inflammatory Pain and Enhances the Analgesic Properties of Delta Opioid Receptors Subject: Chronic inflammatory pain is present in many pathologies and diminishes the patient’s quality of life. Moreover, most current treatments have a low efficacy and significant side effects. Recent studies demonstrate the analgesic properties of slow-releasing hydrogen sulfide (H2S) donors in animals with osteoarthritis or neuropathic pain, but their effects in inflammatory pain and related pathways are not completely understood. Several treatments potentiate the analgesic actions of -opioid receptor (DOR) agonists, but the role of H2S in modulating their effects and expression during inflammatory pain remains untested. In C57BL/6J male mice with inflammatory pain provoked by subplantar injection of complete Freund’s adjuvant, we evaluated: (1) the antiallodynic and antihyperalgesic effects of different doses of two slow-releasing H2S donors, i.e., diallyl disulfide (DADS) and phenyl isothiocyanate (P-ITC) and their mechanism of action; (2) the pain-relieving effects of DOR agonists co-administered with H2S donors; (3) the effects of DADS and P-ITC on the oxidative stress and molecular changes caused by peripheral inflammation. Results demonstrate that both H2S donors inhibited allodynia and hyperalgesia in a dose-dependent manner, potentiated the analgesic effects and expression of DOR, activated the antioxidant system, and reduced the nociceptive and apoptotic pathways. The data further demonstrate the possible participation of potassium channels and the Nrf2 transcription factor signaling pathway in the pain-relieving activities of DADS and P-ITC. This study suggests that the systemic administration of DADS and P-ITC and local application of DOR agonists in combination with slow-releasing H2S donors are two new strategies for the treatment of inflammatory pain. Keywords: analgesia; antioxidants; delta opioid receptors; inflammation; oxidative stress; pain Author: Aina Porta, Laura Rodríguez, Xue Bai, Gerard Batallé, Gerad Roch, Enric Pouso-Vázquez, Gianfranco Balboni and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 17 14:56:31 2021 CET ModDate: Fri Dec 17 15:00:42 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3447525 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IOJCNK+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 HKBJPQ+VnURWPalladioL Type 1 Custom yes yes no 15 0 XIKBSM+EURM10 Type 1 Builtin yes yes no 19 0 JCXLAH+URWPalladioL-Ital Type 1 Custom yes yes no 23 0 GKZXYE+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 ZCHWYC+URWPalladioL-Roma Type 1 Custom yes 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yes no 377 0 TimesNewRomanPSMT TrueType WinAnsi no no no 381 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2022-03-22 02:27:57 CET RepresentationInformation: pmc_34943080.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-01-17 03:39:52 CET Size: 3447525 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 617 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Induction of Inflammatory Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Mechanical Allodynia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Thermal Hyperalgesia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Preparation of Whole-Cell Extracts and 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: Effects of the Acute Administration of DADS and P-ITC in the Mechanical Allodynia and Thermal Hyperalgesia Induced by CFA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Reversion of the Antiallodynic and Antihyperalgesic Effects Induced by High Doses of DADS or P-ITC with Their Co-Administration with Two Potassium Channels Inhibitors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Reversion of the Antiallodynic and Antihyperalgesic Effects Induced by High Doses of DADS or P-ITC with Their Co-Administration with Specific Inhibitors of the Nrf2/HO-1-NQO1 Signaling Pathway Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Effects of Treatment with DADS and P-ITC on the Expression of 4-HNE in the Paws of Animals with Peripheral Inflammation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Effects of Treatment with DADS and P-ITC on the Expression of HO-1, NQO1, SOD-1, and GSTM1 in the Paws of Mice with Peripheral Inflammation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Effects of Treatment with DADS and P-ITC on the Expression of p-AKT, BAX, and DOR in the Paws of Animals with Peripheral Inflammation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Effects of the Acute Administration of DPDPE and UFP-512 in the Mechanical Allodynia and Thermal Hyperalgesia Induced by CFA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Enhancement of the Antinociceptive Actions Generated by the Subplantar Administration of DPDPE and UFP-512 during Inflammatory Pain in Mice Treated with DADS or P-ITC 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 Sulfide Inhibits Inflammatory Pain and Enhances the Analgesic Properties of Delta Opioid Receptors Author: Aina Porta, Laura Rodríguez, Xue Bai, Gerard Batallé, Gerad Roch, Enric Pouso-Vázquez, Gianfranco Balboni and Olga Pol Subject: Chronic inflammatory pain is present in many pathologies and diminishes the patient’s quality of life. Moreover, most current treatments have a low efficacy and significant side effects. Recent studies demonstrate the analgesic properties of slow-releasing hydrogen sulfide (H2S) donors in animals with osteoarthritis or neuropathic pain, but their effects in inflammatory pain and related pathways are not completely understood. Several treatments potentiate the analgesic actions of -opioid receptor (DOR) agonists, but the role of H2S in modulating their effects and expression during inflammatory pain remains untested. In C57BL/6J male mice with inflammatory pain provoked by subplantar injection of complete Freund’s adjuvant, we evaluated: (1) the antiallodynic and antihyperalgesic effects of different doses of two slow-releasing H2S donors, i.e., diallyl disulfide (DADS) and phenyl isothiocyanate (P-ITC) and their mechanism of action; (2) the pain-relieving effects of DOR agonists co-administered with H2S donors; (3) the effects of DADS and P-ITC on the oxidative stress and molecular changes caused by peripheral inflammation. Results demonstrate that both H2S donors inhibited allodynia and hyperalgesia in a dose-dependent manner, potentiated the analgesic effects and expression of DOR, activated the antioxidant system, and reduced the nociceptive and apoptotic pathways. The data further demonstrate the possible participation of potassium channels and the Nrf2 transcription factor signaling pathway in the pain-relieving activities of DADS and P-ITC. This study suggests that the systemic administration of DADS and P-ITC and local application of DOR agonists in combination with slow-releasing H2S donors are two new strategies for the treatment of inflammatory pain. 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