Hydrogen Sulfide Increases the Analgesic Effects of μ- and δ-Opioid Receptors during Neuropathic Pain : Pathways Implicated
Bai, Xue (Universitat Autònoma de Barcelona. Institut de Neurociències)
Batallé Melgarejo, Gerard (Universitat Autònoma de Barcelona. Institut de Neurociències)
Balboni, Gianfranco (University of Cagliari. Department of Life and Environmental Sciences)
Pol, Olga (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2022
Resum:	Recent studies have revealed that hydrogen sulfide (H2S) increases the analgesic actions of the δ-opioid receptor (DOR) in inflammatory pain. However, the possible improvement of the analgesia of μ-opioid receptor (MOR) and DOR agonists during neuropathic pain, through pretreat-ment with two slow-releasing H2S donors-DADS (diallyl disulfide) and GYY4137 (morpholin-4- ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex)-is still un-known. In male C57BL/6J mice with neuropathic pain incited by chronic constriction of the sciatic nerve (CCI), we evaluated: (1) the influence of DADS (3. 5 mg/kg) and GYY4137 (0. 7 mg/kg) on the inhibition of the allodynia and hyperalgesia produced by the systemic or local administration of morphine (3 mg/kg or 65 μg) and UFP-512 (1 mg/kg or 12. 5 μg); (2) the reversion of the antinocicep-tive actions of high doses of DADS (30 mg/kg) and GYY4137 (24 mg/kg) with MOR and DOR an-tagonists; and (3) the effects of H2S donors on oxidative stress, apoptotic responses, and MOR and DOR expression in the medial septum (MS) and dorsal root ganglia (DRG). The results revealed that both DADS and GYY4137 improved the antiallodynic effects of morphine and UFP-512, possi-bly by up-regulating MOR and DOR expression in DRG. The administration of MOR and DOR antagonists blocked the analgesic properties of DADS and GYY4137, revealing the feasible partici-pation of the endogenous opioid system in H2S analgesic effects. Moreover, both H2S donors inhibited oxidative stress and apoptosis generated by CCI in the MS and/or DRG. This study suggests the co-treatment of H2S donors with MOR or DOR agonists as a potential therapy for neuropathic pain.
Ajuts:	Instituto de Salud Carlos III PI18/00645 Instituto de Salud Carlos III PI21/00592
Nota:	This work was supported by Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, and Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea [Grants: PI18/00645 and PI21/00592].
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Antioxidants, Vol. 11 Núm. 7 (july 2022) , p. 1321, ISSN 2076-3921

DOI: 10.3390/antiox11071321
PMID: 35883812

17 p, 5.0 MB

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