Sugammadex Potentiation of Morphine Analgesia and Reduction of Opioid Tolerance Is Accompanied by Inhibition of Oxidative Stress and the NLRP3/IL-1β Signaling Pathway in the Rat Dorsal Root Ganglion.

Recent studies have shown that sugammadex's effects on the nervous system are controversial and its effect on nociception, morphine analgesia and tolerance is still unclear. The current study aimed to examine the possible involvement of sugammadex on nociception, morphine analgesia, and morphine tolerance development involving oxidative stress and NOD-like receptor protein 3 (NLRP3)/Interleukin-1β (IL-1β) signaling pathways in rats. The animals, thirty-six male Wistar Albino rats, were separated into six groups (n = 6 for each group): saline, sugammadex, morphine, morphine + sugammadex, morphine tolerance, and morphine tolerance + sugammadex. The analgesic effects were measured by analgesia tests (the tail-flick and hot plate). Oxidative stress parameters, NLRP3/IL-1β signaling pathway, and apoptotic proteins in the dorsal root ganglion (DRG) tissues were measured using Enzyme-Linked ImmunoSorbent Assay (ELISA) kits. Sugammadex had no antinociceptive activity when administered alone. However, it improved morphine's analgesic efficacy and inhibited the development of morphine tolerance. In addition, it decreased oxidative stress and NLRP3/IL-1β signaling pathway proteins in the DRG when administered with single and repeated doses of morphine. Besides, sugammadex lowered apoptotic proteins in the DRG following tolerance development. Thus, we may conclude that the ability of sugammadex to affect morphine pharmacological activity may be mediated by the suppression of oxidative stress and the NLRP3/IL-1β pathway. [ABSTRACT FROM AUTHOR]