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Sumatriptan improves the locomotor activity and neuropathic pain by modulating neuroinflammation in rat model of spinal cord injury.
Neurological Research ( IF 1.7 ) Pub Date : 2020-09-16 , DOI: 10.1080/01616412.2020.1819090
Khashayar Afshari 1, 2 , Amir Dehdashtian 1, 2 , Nazgol-Sadat Haddad 2 , Seyedeh Zarifeh Jazaeri 1 , Daniel C Ursu 3 , Mina Khalilzadeh 2 , Arvin Haj-Mirzaian 1, 2 , Saeed Shakiba 1, 2 , Terry C Burns 4 , Seyed Mohammad Tavangar 5, 6 , Mehdi Ghasemi 7 , Ahmad Reza Dehpour 2, 8
Affiliation  

ABSTRACT

Objectives

To investigate the therapeutic effects of sumatriptan in a rat model of spinal cord injury (SCI) and possible anti-inflammatory and analgesic mechanisms underlying this effect.

Methods

Using an aneurysm mini-clip model of contusive SCI, T9-10 laminectomies were performed for 60 male rats. Animals were divided into six experimental groups (n = 10 per group) as follows: a minocycline administered positive control group, a saline-vehicle negative control group, a sham-operated group, and three experimental groups which received separate doses of sumatriptan (0.1, 0.3 and 1 mg/kg). Behavioural assessments were used to evaluate locomotor activity and neuropathic pain for 28 days. At the end of the study, spinal cord tissues were collected from sacrificed animals for histopathological analysis. Levels of calcitonin gene-related peptide (CGRP) and two pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1β) were assessed by the enzyme-linked immunosorbent assay (ELISA).

Results

Sumatriptan significantly (P < 0.001) improved the locomotor activity in SCI group. Sumatriptan was also more effective than the positive control, i.e. minocycline (0.3 mg/kg). Additionally, sumatriptan and minocycline similarly attenuated the mechanical and thermal allodynia in SCI (P < 0.001). TNF-α, IL-1β and CGRP levels in sumatriptan- and minocycline-treated groups significantly (P < 0.001) decreased compared to controls. Histopathological analysis also revealed a markedly improvement in hemorrhage followed by inflammatory cell invasion, neuronal vacuolation, and cyst formation in both sumatriptan- and minocycline-treated groups compared to control animals.

Conclusions

Sumatriptan improves functional recovery from SCI through its anti-inflammatory effects and reducing pro-inflammatory and pain mediators.



中文翻译:

舒马曲坦通过调节脊髓损伤大鼠模型中的神经炎症来改善运动活动和神经性疼痛。

摘要

目标

研究舒马曲坦在脊髓损伤 (SCI) 大鼠模型中的治疗作用以及这种作用背后可能的抗炎和镇痛机制。

方法

使用挫伤性 SCI 的动脉瘤微型夹模型,对 60 只雄性大鼠进行了 T9-10 椎板切除术。动物被分为六个实验组(每组n = 10):一个给予米诺环素的阳性对照组、一个盐水载体阴性对照组、一个假手术组和三个接受单独剂量的舒马曲坦(0.1 、0.3 和 1 毫克/千克)。行为评估用于评估 28 天的运动活动和神经性疼痛。在研究结束时,从处死的动物中收集脊髓组织用于组织病理学分析。通过酶联免疫吸附试验 (ELISA) 评估降钙素基因相关肽 (CGRP) 和两种促炎细胞因子(肿瘤坏死因子 [TNF] -α 和白细胞介素 [IL] -1β)的水平。

结果

舒马曲坦显着(P <0.001)改善了SCI组的运动活动。舒马曲坦也比阳性对照更有效,即米诺环素 (0.3 mg/kg)。此外,舒马曲坦和米诺环素同样可以减轻 SCI 的机械性和热性异常性疼痛(P <0.001)。与对照组相比,舒马曲坦和米诺环素治疗组的 TNF-α、IL-1β 和 CGRP 水平显着降低(P <0.001)。组织病理学分析还显示,与对照动物相比,舒马曲坦和米诺环素治疗组的出血显着改善,随后炎症细胞侵袭、神经元空泡形成和囊肿形成。

结论

舒马曲坦通过其抗炎作用和减少促炎和疼痛介质来改善 SCI 的功能恢复。

更新日期:2020-09-16
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