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鞘内给予右美托咪定产生抗伤害作用,且不会在大鼠中引起神经毒性。

Intracerebroventricular Application of Dexmedetomidine Produces Antinociception and Does not Cause Neurotoxicity in Rats.

机构信息

Department of Anesthesiology and Reanimation, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.

Department of Pathology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.

出版信息

Balkan Med J. 2013 Dec;30(4):355-61. doi: 10.5152/balkanmedj.2013.7747. Epub 2013 Dec 1.

DOI:10.5152/balkanmedj.2013.7747
PMID:25207141
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4115944/
Abstract

BACKGROUND

Alpha2 agonists contribute to pain control at the level of the medulla spinalis. Alpha2 agonists are generally added to local anaesthetics to prolong spinal or epidural anaesthesia time.

AIMS

In the present study, we aimed to evaluate the antinociceptive and neurotoxic effects of dexmedetomidine given intracerebroventricularly for 5 days.

STUDY DESIGN

Animal experimentation.

METHODS

After intraventricular cannulation, rats (n=32) were divided into two groups (n=16 each). Rats in the dexmedetomidine group (Group D, n=16) received 3 µg (0.03 mL) dexmedetomidine and the control group (Group C, n=16) received 0.03 mL physiological serum through an intracerebroventricular catheter once a day, for 5 days. Antinociceptive, sedative, and motor effects were evaluated before the injection and for 90 min after injection. The tail-flick and hot plate tests were used to assess thermal nociceptive threshold. For histopathological evaluation, half of the rats in both groups were sacrificed on the 6(th) day and the remaining rats were sacrificed on the 21(st) day. Then the perfusion fixation method was applied. The first tissue section was obtained from the cervical spinal cord 1 cm distal to the proximal end of the spinal cord. The second sample was retrieved from the region 1 cm distal from the thoracic 13-lumbar 1 vertebra. On morphological evaluation, nonspecific changes like edema and gliosis, signs of neuronal degeneration demonstrating a severe reaction, and density of inflammatory cells were examined.

RESULTS

In dexmedetomidine-administered rats, on the first day reaction times at 5, 10, and 20 min and on the other days, reaction times at 5, 10, 20, and 30 min in hot plate tests were significantly longer compared with baseline values (p<0.05). In dexmedetomidine-administered rats, on the 1(st), 4(th), and 5(th) days reaction times at 5, 10, 20, 30, and 40 min and on the 2(nd) and 3(rd) days reaction times at 5, 10, 20, and 30 min in tail-flick tests were significantly longer compared with baseline values (p<0.05). First-degree sedation lasting for 60 min and first-degree motor block lasting for 30-40 min were observed in the dexmedetomidine group. Similar rates of nonspecific changes such as edema and gliosis were seen in both groups. Signs of severe reactions such as neuronal degeneration and diffuse inflammatory cell infiltration were not encountered in any group. There was no significant difference between groups according to morphological findings of the spinal cord on the 6(th) and 21(st) days (p>0.05).

CONCLUSION

We observed that intracerebroventricular administration of 3 μg dexmedetomidine produced antinociception and did not cause neurotoxicity.

摘要

背景

α2 激动剂在脊髓水平有助于控制疼痛。α2 激动剂通常添加到局部麻醉剂中以延长脊髓或硬膜外麻醉时间。

目的

本研究旨在评估鞘内给予右美托咪定 5 天的抗伤害感受和神经毒性作用。

研究设计

动物实验。

方法

在脑室插管后,将大鼠(n=32)分为两组(每组 n=16)。右美托咪定组(D 组,n=16)通过脑室导管每天接受 3 µg(0.03 mL)右美托咪定,对照组(C 组,n=16)接受 0.03 mL 生理血清。在注射前和注射后 90 分钟评估镇痛、镇静和运动效果。使用尾巴闪烁和热板试验评估热伤害感受阈值。为了进行组织病理学评估,两组中有一半的大鼠在第 6 天被处死,其余的大鼠在第 21 天被处死。然后应用灌注固定方法。从脊髓近端 1 cm 处获得第一块颈椎脊髓组织切片。第二个样本取自胸 13 腰 1 椎骨 1 cm 远端。在形态学评估中,检查了非特异性变化,如水肿和神经胶质增生、神经元变性的严重反应迹象以及炎症细胞密度。

结果

在鞘内给予右美托咪定的大鼠中,在热板试验中,第 1 天 5、10 和 20 分钟时以及其他天 5、10、20 和 30 分钟时的反应时间与基线值相比显著延长(p<0.05)。在鞘内给予右美托咪定的大鼠中,在尾巴闪烁试验中,第 1、4 和 5 天 5、10、20、30 和 40 分钟时以及第 2 和 3 天 5、10、20 和 30 分钟时的反应时间与基线值相比显著延长(p<0.05)。在右美托咪定组中观察到持续 60 分钟的 1 级镇静和持续 30-40 分钟的 1 级运动阻滞。两组均观察到类似的非特异性变化率,如水肿和神经胶质增生。在任何一组中均未发现神经元变性和弥漫性炎症细胞浸润等严重反应迹象。根据第 6 天和第 21 天脊髓的形态学发现,两组之间没有显著差异(p>0.05)。

结论

我们观察到鞘内给予 3 µg 右美托咪定可产生镇痛作用,且不会引起神经毒性。

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