The Impact of UFP-512 in Mice with Osteoarthritis Pain : The Role of Hydrogen Sulfide
Batallé Melgarejo, Gerard (Institut de Recerca Sant Pau)
Bai, Xue (Institut de Recerca Sant Pau)
Balboni, Gianfranco (Universitá di Cagliari. Dipartimento della Vita e dell'Ambiente)
Pol, Olga (Universitat Autònoma de Barcelona. Institut de Neurociències)
Data: |
2023 |
Resum: |
The pain-relieving properties of opioids in inflammatory and neuropathic pain are heightened by hydrogen sulfide (HS). However, whether allodynia and functional and/or emotional impairments related to osteoarthritis (OA) could be reduced by activating δ-opioid receptors (DOR) and the plausible influence of HS 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 HS 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-IKBα) and the antioxidant enzymes superoxide dismutase 1 (SOD-1) and glutathione sulfur transferase M1 (GSTM1); and the effects of HS 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 HS and reversed by naltrindole. UFP-512 also inhibited anxiodepressive-like behaviors, normalized the overexpression of p-IKBα 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 HS might support the improved analgesic actions of UFP-512 co-administered with HS donors. This study proposes the use of DOR agonists, alone or combined with HS donors, as a new treatment for OA pain. |
Ajuts: |
Instituto de Salud Carlos III PI18/00645 Instituto de Salud Carlos III PI21/00592
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Drets: |
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Llengua: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Matèria: |
Analgesia ;
Antioxidants ;
Anxiety ;
Δ-opioid receptors ;
Depression ;
Osteoarthritis pain ;
Oxidative stress |
Publicat a: |
Antioxidants, Vol. 12, Num. 12 (december 2023) , ISSN 2076-3921 |
DOI: 10.3390/antiox12122085
PMID: 38136204
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Registre creat el 2024-02-13, darrera modificació el 2024-05-04