b822dc7b61a71123074d4ce87101fdf1 pmc_34356307.pdf ab1ef3a2b983d9fcc1923ee2b388f938d073bc35 pmc_34356307.pdf c2fa95a0705e5c313d4f6796873b312ed626fbe6ad2f04d94e8cfdab5ea8b3d7 pmc_34356307.pdf Title: The Anxiolytic and Antidepressant Effects of Diallyl Disulfide and GYY4137 in Animals with Chronic Neuropathic Pain Subject: When neuropathic pain is maintained long term, it can also lead to the development of emotional disorders that are even more intense than pain perception and difficult to treat. Hydrogen sulfide (H2S) donors relieve chronic pain, but their effects on the associated mood disorders are not completely elucidated. We evaluated if treatment with DADS (diallyl disulfide) or GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex), two slow-releasing H2S donors, inhibits the anxiety- and depressive-like behaviors that concur with chronic neuropathic pain generated by sciatic nerve injury in mice. The modulatory role of these drugs in the inflammatory, apoptotic, and oxidative processes implicated in the development of the affective disorders was assessed. Our results revealed the anxiolytic, antidepressant, and antinociceptive properties of DADS and GYY4137 during neuropathic pain by inhibiting microglial activation and the up-regulation of phosphoinositide 3-kinase/phosphorylated protein kinase B and BAX in the amygdala (AMG) and/or periaqueductal gray matter (PAG). Both treatments also normalized and/or activated the endogenous antioxidant system, but only DADS blocked ERK 1/2 phosphorylation. Both H2S donors decreased allodynia and hyperalgesia in a dose-dependent manner by activating the Kv7 potassium channels and heme oxygenase 1 signaling pathways. This study provides evidence of the anxiolytic and antidepressant properties of DADS and GYY4137 during neuropathic pain and reveals their analgesic actions, suggesting that these therapeutic properties may result from the inhibition of the inflammatory, apoptotic, and oxidative responses in the AMG and/or PAG. These findings support the use of these treatments for the management of affective disorders accompanying chronic neuropathic pain. Keywords: anxiety; apoptosis; depression; hydrogen sulfide; neuropathic pain; oxidative stress Author: Xue Bai, Gerard Batallé and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jul 6 07:54:53 2021 CEST ModDate: Tue Jul 6 08:00:57 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4556786 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MWHIBA+VnURWPalladioL Type 1 Custom yes yes no 10 0 WSDFYA+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 MJDHBR+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 VDIPZP+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes 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no 279 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-27 02:42:24 CEST RepresentationInformation: pmc_34356307.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-03-31 12:14:43 CEST Size: 4556786 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 567 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 Methods 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 Behavioral Tests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Depressive Behavioral Tests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Western Blot Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Experimental Procedures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Drugs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Statistical Analyses 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: Anxiolytic and Antidepressant Effects of DADS and GYY4137 in Animals with Chronic Neuropathic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: The Acute Administration of DADS and GYY4137 Inhibited Mechanical Allodynia, Thermal Hyperalgesia, and Cold Allodynia Induced by Sciatic Nerve Injury in a Dose-Dependent Manner Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Reversion of the Antinociceptive Effects of DADS and GYY4137 with the Administration of XE-991 or SnPP Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Effects of Treatment with DADS and GYY4137 in the Protein Levels of PI3K, p-Akt, p-ERK 1/2, CD11b/c, and BAX in the AMG and PAG of Mice with Neuropathic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Effects of Treatment with DADS and GYY4137 on the Protein Levels of HO-1, NQO1, SOD-1, and GSTM1 in the AMG and PAG of Mice with Neuropathic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Info: Title: The Anxiolytic and Antidepressant Effects of Diallyl Disulfide and GYY4137 in Animals with Chronic Neuropathic Pain Author: Xue Bai, Gerard Batallé and Olga Pol Subject: When neuropathic pain is maintained long term, it can also lead to the development of emotional disorders that are even more intense than pain perception and difficult to treat. Hydrogen sulfide (H2S) donors relieve chronic pain, but their effects on the associated mood disorders are not completely elucidated. We evaluated if treatment with DADS (diallyl disulfide) or GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex), two slow-releasing H2S donors, inhibits the anxiety- and depressive-like behaviors that concur with chronic neuropathic pain generated by sciatic nerve injury in mice. The modulatory role of these drugs in the inflammatory, apoptotic, and oxidative processes implicated in the development of the affective disorders was assessed. Our results revealed the anxiolytic, antidepressant, and antinociceptive properties of DADS and GYY4137 during neuropathic pain by inhibiting microglial activation and the up-regulation of phosphoinositide 3-kinase/phosphorylated protein kinase B and BAX in the amygdala (AMG) and/or periaqueductal gray matter (PAG). Both treatments also normalized and/or activated the endogenous antioxidant system, but only DADS blocked ERK 1/2 phosphorylation. Both H2S donors decreased allodynia and hyperalgesia in a dose-dependent manner by activating the Kv7 potassium channels and heme oxygenase 1 signaling pathways. This study provides evidence of the anxiolytic and antidepressant properties of DADS and GYY4137 during neuropathic pain and reveals their analgesic actions, suggesting that these therapeutic properties may result from the inhibition of the inflammatory, apoptotic, and oxidative responses in the AMG and/or PAG. These findings support the use of these treatments for the management of affective disorders accompanying chronic neuropathic pain. 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Annotation: Subtype: Link Rect: 221, 469, 258, 479 Annotation: Subtype: Link Rect: 265, 469, 301, 479 Annotation: Subtype: Link Rect: 131, 446, 169, 456 Annotation: Subtype: Link Rect: 95, 411, 133, 421 Annotation: Subtype: Link Rect: 139, 411, 175, 421 Annotation: Subtype: Link Rect: 319, 387, 357, 398 Annotation: Subtype: Link Rect: 59, 319, 97, 329 Annotation: Subtype: Link Rect: 462, 295, 500, 306 Annotation: Subtype: Link Rect: 234, 272, 271, 283 Annotation: Subtype: Link Rect: 277, 272, 313, 283 Annotation: Subtype: Link Rect: 407, 249, 445, 260 Annotation: Subtype: Link Rect: 59, 215, 97, 226 Annotation: Subtype: Link Rect: 103, 215, 139, 226 Annotation: Subtype: Link Rect: 59, 181, 97, 191 Annotation: Subtype: Link Rect: 95, 158, 132, 168 Annotation: Subtype: Link Rect: 139, 158, 175, 168 Checksum: 7c49ae84 Type: CRC32 Checksum: b822dc7b61a71123074d4ce87101fdf1 Type: MD5 Checksum: ab1ef3a2b983d9fcc1923ee2b388f938d073bc35 Type: SHA-1