Department of Orthopedics and Traumatology, 25 Aralık State Hospital, Gaziantep 27060, Turkey.
Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, Turkey.
Medicina (Kaunas). 2023 Oct 9;59(10):1793. doi: 10.3390/medicina59101793.
: The purpose of the study was to investigate the role of adrenaline (ADR), noradrenaline (NDR), and cortisol in the pathogenesis of the analgesic potency, duration, and epilepsy-like toxic effect of meperidine. : The experimental animals were separated into 11 groups of six rats. In the meperidine (MPD) and metyrosine + meperidine (MMPD) groups, paw pain thresholds were measured before and after the treatment between the first and sixth hours (one hour apart). In addition, ADR and NDR analyses were performed before and after the treatment, between the first and fourth hours (one hour apart). For the epilepsy experiment, caffeine, caffeine + meperidine, and caffeine + meperidine + metyrapone groups were created, and the treatment was applied for 1 day or 7 days. Groups were created in which caffeine was used at both 150 mg/kg and 300 mg/kg. Epileptic seizures were observed in epilepsy groups, latent periods were determined, and serum cortisol levels were measured. : In the MPD group, pain thresholds increased only at the first and second hours compared to pre-treatment, while ADR increased at the third hour, leading to a decrease in pain thresholds. In the MMPD group, the increase in paw pain thresholds at 1 and 6 h was accompanied by a decrease in ADR and NDR. In the caffeine (150 mg/kg) + meperidine group, 1-day treatment did not cause epileptic seizures, while seizures were observed and cortisol levels increased in the group in which treatment continued for 7 days. When cortisol levels were compared between the group in which caffeine (300 mg/kg) + meperidine + metyrapone was used for 7 days and the animals receiving caffeine (300 mg/kg) + metyrapone for 7 days, it was found that cortisol levels decreased and the latent period decreased. : The current study showed that if serum ADR and cortisol levels are kept at normal levels, a longer-lasting and stronger analgesic effect can be achieved with meperidine, and epileptic seizures can be prevented.
: 本研究旨在探讨肾上腺素（ADR）、去甲肾上腺素（NDR）和皮质醇在哌替啶的镇痛效力、持续时间和癫痫样毒性作用的发病机制中的作用。 : 将实验动物分为 11 组，每组 6 只大鼠。在哌替啶（MPD）和甲酪氨酸+哌替啶（MMPD）组中，在治疗前后（每隔 1 小时）测量第 1 至第 6 小时之间的足痛阈值。此外，在治疗前后（每隔 1 小时）进行 ADR 和 NDR 分析。对于癫痫实验，创建了咖啡因、咖啡因+哌替啶和咖啡因+哌替啶+美替拉酮组，治疗应用于 1 天或 7 天。创建了使用 150mg/kg 和 300mg/kg 咖啡因的组。观察癫痫组的癫痫发作，确定潜伏期，并测量血清皮质醇水平。 : 在 MPD 组中，与治疗前相比，只有在第 1 小时和第 2 小时疼痛阈值才会增加，而在第 3 小时 ADR 增加，导致疼痛阈值降低。在 MMPD 组中，第 1 小时和第 6 小时足痛阈值的增加伴随着 ADR 和 NDR 的降低。在咖啡因（150mg/kg）+哌替啶组中，1 天治疗不会引起癫痫发作，而继续治疗 7 天的组则观察到癫痫发作和皮质醇水平升高。将使用咖啡因（300mg/kg）+美替拉酮治疗 7 天的组与接受咖啡因（300mg/kg）+美替拉酮治疗 7 天的动物的皮质醇水平进行比较，发现皮质醇水平降低，潜伏期缩短。 : 本研究表明，如果保持血清 ADR 和皮质醇水平正常，哌替啶可以产生更持久和更强的镇痛作用，并预防癫痫发作。
