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

IF 0.5 4区 医学 Q4 NEUROSCIENCES
Ahmet Sevki Taskiran, Onur Avci
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引用次数: 0

Abstract

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 Image

抑制大鼠背根神经节中的氧化应激和 NLRP3/IL-1β 信号通路可增强吗啡镇痛和降低阿片类药物耐受性
摘要近期的研究表明,舒甘美对神经系统的影响存在争议,其对痛觉、吗啡镇痛和耐受性的影响仍不明确。本研究旨在探讨苏甘美对大鼠痛觉、吗啡镇痛和吗啡耐受性发展的可能影响,其中涉及氧化应激和NOD样受体蛋白3(NLRP3)/白细胞介素-1β(IL-1β)信号通路。将36只雄性Wistar Albino大鼠分为六组(每组n=6):生理盐水组、苏格玛德克斯组、吗啡组、吗啡+苏格玛德克斯组、吗啡耐受组和吗啡耐受+苏格玛德克斯组。镇痛效果通过镇痛测试(尾晕和热板)进行测量。使用酶联免疫吸附试验(ELISA)试剂盒测定了背根神经节(DRG)组织中的氧化应激参数、NLRP3/IL-1β信号通路和凋亡蛋白。单独给药时,舒甘麦迪没有抗痛觉活性。但是,它能提高吗啡的镇痛效果,并抑制吗啡耐受性的产生。此外,与单剂量和重复剂量吗啡同时服用时,它还能降低DRG中的氧化应激和NLRP3/IL-1β信号通路蛋白。此外,在产生耐受性后,苏甘麦克斯还能降低DRG中的凋亡蛋白。因此,我们可以得出结论,舒降之影响吗啡药理活性的能力可能是通过抑制氧化应激和NLRP3/IL-1β通路介导的。
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来源期刊
Neurochemical Journal
Neurochemical Journal 医学-神经科学
自引率
20.00%
发文量
40
审稿时长
>12 weeks
期刊介绍: Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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