779a26f3457c6cc3e0bdb0f42d798e5b pmc_10740868.pdf fc93b3f45e02d51e405a372395dd6922a29108c5 pmc_10740868.pdf 1c075ae37dce6c9d8ee6c2a22536aec81da978d6b133509c92d38ea69f8aaccd pmc_10740868.pdf Title: The Impact of UFP-512 in Mice with Osteoarthritis Pain: The Role of Hydrogen Sulfide Subject: The pain-relieving properties of opioids in inflammatory and neuropathic pain are heightened by hydrogen sulfide (H2S). However, whether allodynia and functional and/or emotional impairments related to osteoarthritis (OA) could be reduced by activating -opioid receptors (DOR) and the plausible influence of H2S on these actions has not been completely established. In female C57BL/6J mice with OA pain generated via monosodium acetate (MIA), we analyze: (i) the effects of UFP-512 (a DOR agonist), given alone and co-administered with two H2S donors, on the symptoms of allodynia, loss of grip strength (GS), and anxiodepressive-like comportment; (ii) the reversion of UFP-512 actions with naltrindole (a DOR antagonist), and (iii) the impact of UFP-512 on the expression of phosphorylated NF-kB inhibitor alpha (p-IKB) and the antioxidant enzymes superoxide dismutase 1 (SOD-1) and glutathione sulfur transferase M1 (GSTM1); and the effects of H2S on DOR levels in the dorsal root ganglia (DRG), amygdala (AMG), and hippocampus (HIP) of MIA-injected animals. Results showed that systemic and local administration of UFP-512 dose-dependently diminished the allodynia and loss of GS caused by MIA, whose effects were potentiated by H2S and reversed by naltrindole. UFP-512 also inhibited anxiodepressive-like behaviors, normalized the overexpression of p-IKB in DRG and HIP, and enhanced the expression of SOD-1 and GSTM1 in DRG, HIP, and/or AMG. Moreover, the increased expression of DOR triggered by H2S might support the improved analgesic actions of UFP-512 co-administered with H2S donors. This study proposes the use of DOR agonists, alone or combined with H2S donors, as a new treatment for OA pain. Keywords: analgesia; antioxidants; anxiety; -opioid receptors; depression; osteoarthritis pain; oxidative stress Author: Gerard Batallé, Xue Bai, Gianfranco Balboni and Olga Pol Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Dec 7 06:47:24 2023 CET ModDate: Thu Dec 7 06:53:51 2023 CET Custom Metadata: no Metadata Stream: no 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: 2535217 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 RTJQYV+EURM10 Type 1 Builtin yes yes no 15 0 BUKZGR+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 SFRLGN+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 OPYAQE+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 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LastModified: 2024-02-13 02:34:50 CET Size: 2535217 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 632 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Method Destination: section.2 Children: Item: Title: Animals Destination: subsection.2.1 Item: Title: Materials Destination: subsection.2.2 Item: Title: The Induction of OA Pain Destination: subsection.2.3 Item: Title: Allodynia and GS Measurements Destination: subsection.2.4 Item: Title: Affective Behaviors Destination: subsection.2.5 Item: Title: Western Blotting Analysis Destination: subsection.2.6 Item: Title: Experimental Protocol Destination: subsection.2.7 Item: Title: Data Analyses Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: Treatment with UFP-512 Inhibits the Allodynia and GS Deficts Caused by MIA Destination: subsection.3.1 Item: Title: The Impact of UFP-512 on the Affective Disorders Associated with OA Pain and Its Reversion with Naltrindole Destination: subsection.3.2 Item: Title: Effects of Treatment with UFP-512 on p-IKB, SOD-1 and GSTM1 Levels in the DRG, AMG and HIP of Mice with OA Pain Destination: subsection.3.3 Item: Title: Effects of Treatment with UFP-512 plus H2S Donors on Allodynia and GS Deficits Provoked by MIA Destination: subsection.3.4 Item: Title: Impact of H2S on Levels of DORs in the DRG, AMG and HIP of MIA-Injected Mice Destination: subsection.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: The Impact of UFP-512 in Mice with Osteoarthritis Pain: The Role of Hydrogen Sulfide Author: Gerard Batallé, Xue Bai, Gianfranco Balboni and Olga Pol Subject: The pain-relieving properties of opioids in inflammatory and neuropathic pain are heightened by hydrogen sulfide (H2S). However, whether allodynia and functional and/or emotional impairments related to osteoarthritis (OA) could be reduced by activating -opioid receptors (DOR) and the plausible influence of H2S on these actions has not been completely established. In female C57BL/6J mice with OA pain generated via monosodium acetate (MIA), we analyze: (i) the effects of UFP-512 (a DOR agonist), given alone and co-administered with two H2S donors, on the symptoms of allodynia, loss of grip strength (GS), and anxiodepressive-like comportment; (ii) the reversion of UFP-512 actions with naltrindole (a DOR antagonist), and (iii) the impact of UFP-512 on the expression of phosphorylated NF-kB inhibitor alpha (p-IKB) and the antioxidant enzymes superoxide dismutase 1 (SOD-1) and glutathione sulfur transferase M1 (GSTM1); and the effects of H2S on DOR levels in the dorsal root ganglia (DRG), amygdala (AMG), and hippocampus (HIP) of MIA-injected animals. Results showed that systemic and local administration of UFP-512 dose-dependently diminished the allodynia and loss of GS caused by MIA, whose effects were potentiated by H2S and reversed by naltrindole. UFP-512 also inhibited anxiodepressive-like behaviors, normalized the overexpression of p-IKB in DRG and HIP, and enhanced the expression of SOD-1 and GSTM1 in DRG, HIP, and/or AMG. Moreover, the increased expression of DOR triggered by H2S might support the improved analgesic actions of UFP-512 co-administered with H2S donors. This study proposes the use of DOR agonists, alone or combined with H2S donors, as a new treatment for OA pain. 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