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在神经性疼痛小鼠模型中,莪术二酮通过抑制白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α发挥抗痛觉过敏和抗痛觉超敏作用。

Antiallodynic and antihyperalgesic activities of zerumbone via the suppression of IL-1β, IL-6, and TNF-α in a mouse model of neuropathic pain.

作者信息

Gopalsamy Banulata, Farouk Ahmad Akira Omar, Tengku Mohamad Tengku Azam Shah, Sulaiman Mohd Roslan, Perimal Enoch Kumar

机构信息

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

出版信息

J Pain Res. 2017 Nov 8;10:2605-2619. doi: 10.2147/JPR.S143024. eCollection 2017.

Abstract

BACKGROUND

Neuropathic pain is a debilitating condition that severely affects the quality of life for those with this pain condition, and treatment for pain relief is greatly sought-after. Zerumbone (Zer), a sesquiterpene compound isolated from the rhizomes of a Southeast Asian ginger plant, (L.) Roscoe ex Smith. (Zingiberaceae), showed antinociceptive and antiinflammatory properties when previously tested on models of nociception and inflammation.

OBJECTIVE

This study investigated the effects of prophylactic administration of zerumbone on allodynia and hyperalgesia in a mouse model of chronic constriction injury (CCI)-induced neuropathic pain.

METHODS

Intraperitoneal administration of Zer (5-50 mg/kg) from day 1 post-surgery was carried out to identify the onset and progression of the pain condition. Responses toward mechanical and cold allodynia, and mechanical and thermal hyperalgesia were assessed on days 3, 5, 7, 9, 11, and 14 post-surgery. Blood plasma and spinal cord levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and IL-10 were screened using enzyme-linked immunosorbent assay on day 15.

RESULTS

Zer (10 and 50 mg/kg) attenuated pain symptoms on all days of behavioral testing without any signs of sedation in the rotarod test. ED values for mechanical allodynia, cold allodynia, thermal hyperalgesia, and mechanical hyperalgesia were 9.25, 9.507, 8.289, and 9.801 mg/kg, respectively. Blood plasma and spinal levels of IL-1β, IL-6, and tumor necrosis factor-α but not IL-10 were significantly (<0.05) suppressed by zer treatment.

DISCUSSION AND CONCLUSION

Zer exhibits its antiallodynic and antihyperalgesic properties via reduced sensitization at nociceptor neurons possibly through the suppression of inflammatory mediators. Zer may prove to be a novel and beneficial alternative for the management of neuropathic pain.

摘要

背景

神经性疼痛是一种使人衰弱的病症,严重影响患有这种疼痛病症者的生活质量,因此人们迫切寻求缓解疼痛的治疗方法。莪术酮(Zer)是从一种东南亚姜科植物莪术(Curcuma zedoaria (Christm.) Roscoe ex Smith.)的根茎中分离出的倍半萜化合物,先前在伤害感受和炎症模型上进行测试时显示出抗伤害感受和抗炎特性。

目的

本研究调查了预防性给予莪术酮对慢性缩窄性损伤(CCI)诱导的神经性疼痛小鼠模型中异常性疼痛和痛觉过敏的影响。

方法

从手术后第1天开始腹腔注射莪术酮(5 - 50毫克/千克),以确定疼痛病症的发作和进展。在手术后第3、5、7、9、11和14天评估对机械性和冷异常性疼痛以及机械性和热痛觉过敏的反应。在第15天使用酶联免疫吸附测定法筛选血浆和脊髓中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α和IL-10的水平。

结果

莪术酮(10和50毫克/千克)在行为测试的所有天数均减轻了疼痛症状,在转棒试验中没有任何镇静迹象。机械性异常性疼痛、冷异常性疼痛、热痛觉过敏和机械性痛觉过敏的半数有效剂量(ED)值分别为9.25、9.507、8.289和9.801毫克/千克。莪术酮治疗显著(<0.05)抑制了血浆和脊髓中IL-1β、IL-6和肿瘤坏死因子-α的水平,但未抑制IL-10的水平。

讨论与结论

莪术酮可能通过抑制炎症介质,降低伤害感受器神经元的敏化,从而发挥其抗异常性疼痛和抗痛觉过敏的特性。莪术酮可能被证明是治疗神经性疼痛的一种新型且有益的替代药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b2d/5685132/40b5288244b7/jpr-10-2605Fig1.jpg

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