832bd020ddb3ca046f39c3fb77556362 pmc_10295276.pdf bfa6a9d68b3459e1350e0e688ce6a8102129f179 pmc_10295276.pdf 405a5a6b1721dc05aef7a8f0dec4bdec3b046c9d51b4659287074f2b1340b363 pmc_10295276.pdf Title: Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain Subject: Hydrogen sulfide (H2S) donors make opioids more effective in inhibiting nociception during inflammatory and neuropathic pain. We examined whether the analgesic, anxiolytic and/or antidepressant actions of the cannabinoid 2 receptor (CB2R) agonist, JWH-133, might be improved by pretreatment with H2S donors, DADS and GYY4137 in mice with sciatic nerve injury-provoked neuropathy (CCI). The reversion of the antinociceptive effects of these treatments with the CB2R antagonist, AM630, and the regulatory actions of H2S in the phosphorylation of NF-B inhibitor alpha (IKB) and in the brain-derived neurotrophic factor (BDNF), CB2R, Nrf2 and heme oxygenase 1 (HO-1) levels in prefrontal cortex (PFC), ventral hippocampus (vHIP) and periaqueductal gray matter (PAG), were examined. Data showed that the analgesic effects of JWH-133, systemically and locally administered, were improved by the DADS or GYY4137 pretreatment. The co-treatment of GYY4137 with JWH-133 also stopped anxiodepressive-like activities that concur with neuropathy. Our data likewise showed that both H2S donors normalized the inflammatory (p-IKB), neurotrophic (BDNF) variations caused by CCI, increased the expression of CB2R and activated the Nrf2/HO-1 antioxidant pathway in PFC, v-HIP and/or PAG of animals with neuropathic pain. In addition, the blockade of the analgesia produced by high doses of DADS and GYY4137 with AM630 indicated the contribution of the endocannabinoid system in the effects of H2S during neuropathic pain, thus supporting the positive interaction between H2S and CB2R. Therefore, this study demonstrates the potential use of CB2R agonists combined with H2S donors as a possible treatment for peripheral nerve injury-caused neuropathic pain and the associated emotional disturbances. Keywords: analgesia; anxiety; BDNF; cannabinoids; cannabinoid 2 receptors; depression; hydrogen sulfide; neuropathic pain; oxidative stress Author: Xue Bai, Gerard Batallé, Ignacio Martínez-Martel and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue May 30 08:31:24 2023 CEST ModDate: Tue May 30 09:36:29 2023 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: 4140463 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- HKBJPQ+VnURWPalladioL Type 1 Custom yes yes no 10 0 TFCJSO+EURM10 Type 1 Builtin yes yes no 15 0 KAJKGL+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 RVSFJS+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 HZIDYD+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 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TrueType WinAnsi yes yes no 354 0 FNIDHK+PalatinoLinotype TrueType MacRoman yes yes no 357 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-09-08 02:39:43 CEST RepresentationInformation: pmc_10295276.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-09-02 02:20:42 CEST Size: 4140463 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 673 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: Neuropathic Pain Induction 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: Western Blot Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Experiments 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: The Antinociceptive Effects of JWH-133 during Neuropathic Pain Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: The Analgesic Effects of JWH-133 in Animals with Neuropathic Pain Co-Treated with DADS or GYY4137 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Reversion of the Antinociceptive Actions of JWH-133, DADS and GYY4137 with AM630 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Effects of JWH-133 Alone or Combined with GYY4137 on the Neuropathic-Pain-Associated Anxiodepressive-liked Behaviors Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Effects of DADS and GYY4137 on the p-IKB, BDNF, CB2R, NRF2 and HO-1 Levels in the PFC, vHIP 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: Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain Author: Xue Bai, Gerard Batallé, Ignacio Martínez-Martel and Olga Pol Subject: Hydrogen sulfide (H2S) donors make opioids more effective in inhibiting nociception during inflammatory and neuropathic pain. We examined whether the analgesic, anxiolytic and/or antidepressant actions of the cannabinoid 2 receptor (CB2R) agonist, JWH-133, might be improved by pretreatment with H2S donors, DADS and GYY4137 in mice with sciatic nerve injury-provoked neuropathy (CCI). The reversion of the antinociceptive effects of these treatments with the CB2R antagonist, AM630, and the regulatory actions of H2S in the phosphorylation of NF-B inhibitor alpha (IKB) and in the brain-derived neurotrophic factor (BDNF), CB2R, Nrf2 and heme oxygenase 1 (HO-1) levels in prefrontal cortex (PFC), ventral hippocampus (vHIP) and periaqueductal gray matter (PAG), were examined. Data showed that the analgesic effects of JWH-133, systemically and locally administered, were improved by the DADS or GYY4137 pretreatment. The co-treatment of GYY4137 with JWH-133 also stopped anxiodepressive-like activities that concur with neuropathy. Our data likewise showed that both H2S donors normalized the inflammatory (p-IKB), neurotrophic (BDNF) variations caused by CCI, increased the expression of CB2R and activated the Nrf2/HO-1 antioxidant pathway in PFC, v-HIP and/or PAG of animals with neuropathic pain. In addition, the blockade of the analgesia produced by high doses of DADS and GYY4137 with AM630 indicated the contribution of the endocannabinoid system in the effects of H2S during neuropathic pain, thus supporting the positive interaction between H2S and CB2R. Therefore, this study demonstrates the potential use of CB2R agonists combined with H2S donors as a possible treatment for peripheral nerve injury-caused neuropathic pain and the associated emotional disturbances. 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