Journal
ANTIOXIDANTS
Volume 11, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/antiox11071321
Keywords
analgesia; apoptosis; hydrogen sulfide; neuropathic pain; opioids; oxidative stress
Funding
- Ministerio de Ciencia, Innovacion y Universidades
- Fondo Europeo de Desarrollo Regional (FEDER), Union Europea [PI18/00645, PI21/00592]
- Instituto de Salud Carlos III
Ask authors/readers for more resources
Recent studies have shown that hydrogen sulfide (H2S) enhances the analgesic effects of the delta-opioid receptor (DOR) in inflammatory pain. It is still unknown whether two slow-releasing H2S donors, DADS and GYY4137, can improve the analgesic effects of mu-opioid receptor (MOR) and DOR agonists on neuropathic pain. This study found that both DADS and GYY4137 improved the antiallodynic effects of MOR and DOR agonists, possibly by up-regulating MOR and DOR expression in the dorsal root ganglia.
Recent studies have revealed that hydrogen sulfide (H2S) increases the analgesic actions of the delta-opioid receptor (DOR) in inflammatory pain. However, the possible improvement of the analgesia of mu-opioid receptor (MOR) and DOR agonists during neuropathic pain, through pretreatment with two slow-releasing H2S donors-DADS (diallyl disulfide) and GYY4137 (morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex)-is still unknown. 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 mu g) and UFP-512 (1 mg/kg or 12.5 mu g); (2) the reversion of the antinociceptive actions of high doses of DADS (30 mg/kg) and GYY4137 (24 mg/kg) with MOR and DOR antagonists; 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, possibly 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 participation 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available