fc2ff88a98e42d685d26664d9d0fbb53 antioxidants-12-01859-v3.pdf b5a569bb375973b534899b5fde49d2666e81540c antioxidants-12-01859-v3.pdf 755107a35bc31779968a76fe1b005588716f84ec0afa022dc5d6066e9ea58f81 antioxidants-12-01859-v3.pdf Title: The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated Subject: Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses. Keywords: analgesia; anxiety; depression; dimethyl fumarate; heme oxygenase 1; inflammasome; neuropathic pain; Nrf2 transcription factor; oxidative stress Author: Irene Suárez-Rojas, Montse Pérez-Fernández, Xue Bai, Ignacio Martínez-Martel, Sebastiano Intagliata, Valeria Pittalà, Loredana Salerno and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Oct 23 07:07:45 2023 CEST ModDate: Mon Oct 23 07:11:43 2023 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 8341127 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SYYJVK+VnURWPalladioL Type 1 Custom yes yes no 10 0 HBQXLY+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 RPUNPG+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 FZTOLN+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 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1.12.1 (2019-04-17) LastModified: 2023-11-02 15:16:27 CET Size: 8341127 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 598 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Children: Item: Title: Animals Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Induction of Neuropathic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Nociceptive Behavioral Responses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: Emotional Behavioral Responses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Western Blot Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Drugs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: Experimental Design Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Children: Item: Title: Effects of 1m, 1b, 1a, and DMF Given Orally on the Hyperalgesia and Allodynia Provoked by Sciatic Nerve Injury Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: Impact of the Administration of 1m, 1b, 1a, and DMF on the Anxiety- and Depressive-Related Conducts Accompanying CCI-Provoked Neuropathy in Mice Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: The Impact of 1m, 1b, 1a, and DMF on the Expression of Inflammatory and Antioxidant Proteins in the DRG and AMG of Animals with Neuropathic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6a1aab78 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@462d5aee Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@69b0fd6f Info: Title: The Inhibition of Neuropathic Pain Incited by Nerve Injury and Accompanying Mood Disorders by New Heme Oxygenase-1 Inducers: Mechanisms Implicated Author: Irene Suárez-Rojas, Montse Pérez-Fernández, Xue Bai, Ignacio Martínez-Martel, Sebastiano Intagliata, Valeria Pittalà, Loredana Salerno and Olga Pol Subject: Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses. 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Annotation: Subtype: Link Rect: 339, 319, 375, 330 Annotation: Subtype: Link Rect: 188, 274, 225, 284 Annotation: Subtype: Link Rect: 108, 251, 146, 261 Annotation: Subtype: Link Rect: 152, 251, 188, 261 Annotation: Subtype: Link Rect: 330, 227, 367, 238 Annotation: Subtype: Link Rect: 359, 204, 397, 215 Annotation: Subtype: Link Rect: 403, 204, 439, 215 Annotation: Subtype: Link Rect: 364, 181, 401, 192 Annotation: Subtype: Link Rect: 368, 146, 406, 157 Checksum: 2e2ba6b8 Type: CRC32 Checksum: fc2ff88a98e42d685d26664d9d0fbb53 Type: MD5 Checksum: b5a569bb375973b534899b5fde49d2666e81540c Type: SHA-1