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姜黄素减轻神经病理性疼痛慢性缩窄性损伤模型中的机械性和热痛觉过敏。

Curcumin attenuates mechanical and thermal hyperalgesia in chronic constrictive injury model of neuropathic pain.

机构信息

The Anesthesiology Department of YiChang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, China,

出版信息

Pain Ther. 2014 Jun;3(1):59-69. doi: 10.1007/s40122-014-0024-4. Epub 2014 Mar 13.

Abstract

INTRODUCTION

The aim of this study was to observe the effect of stress caused by neuropathic pain on serum cortisol concentration and expression of 11β-hydroxysteroid dehydrogenase type I enzyme (11βHSD1) in spinal cord and dorsal root ganglions (DRG) and investigate the role and mechanism of curcumin in the neuropathic pain of stressful rats. Neuropathic pain is a prevalent disease that greatly impairs the patients' quality of life. A lack of the understanding of its etiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of curcumin and its effect on expression of 11β-hydroxysteroid dehydrogenase type I enzyme (11βHSD1) in spinal dorsal horn and DRG in chronic constriction injury (CCI) mode of neuropathic pain of rats.

METHODS

Seventy-two male Sprague-Dawley rats were randomized into four groups with 18 rats in each: sham operation group (Sham), chronic constrictive injury group (CCI), solvent contrast group (SC), and curcumin-treated group (Cur100). Curcumin, 100 mg/kg/day intraperitoneal, was given for 14 days starting from the first day after operation in the Cur100 group. Paw thermal withdrawal latency (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured 2 days pre-operative, and 1, 3, 5, 7, 10, and 14 days post-operative. The animals were deeply anesthetized and blood was taken from the heart, the lumbar segment (L4, 5) of the spinal cord and DRG were dissected out and homogenized. The change of cortisol was measured by enzyme-linked immunosorbent assay and the change of 11βHSD1 expression was determined by immunochemistry and Western blot.

RESULTS

Compared with sham group, PTWL and PMWT significantly decrease after operation in the CCI group; serum cortisol concentration was significantly increased and the expression of 11βHSD1 was significantly increased in the CCI group. Comparing with CCI group, the PMWT and PTWL were increased and the serum cortisol concentration was decreased and the expression of 11βHSD1 was inhibited in Cur100 group.

CONCLUSION

Stress caused by neuropathic pain triggers release of cortisol to the blood and expression of 11βHSD1 would increase at the same time. Curcumin could alleviate thermal and mechanical hyperalgesia induced by CCI and inhibit the serum cortisol concentration and expression of 11βHSD1 in the spinal cord and DRG.

摘要

简介

本研究旨在观察神经病理性疼痛引起的应激对血清皮质醇浓度和脊髓及背根神经节(DRG)中 11β-羟类固醇脱氢酶 1 型酶(11βHSD1)表达的影响,并探讨姜黄素在应激大鼠神经病理性疼痛中的作用和机制。神经病理性疼痛是一种常见疾病,极大地降低了患者的生活质量。对其病因缺乏了解、缓解不足、对经典镇痛药物的耐受性和潜在毒性的发展,都需要研究新的药物来缓解这种疼痛。本研究旨在探讨姜黄素的镇痛作用及其对慢性缩窄性损伤(CCI)模式下大鼠神经病理性疼痛时脊髓背角和 DRG 中 11β-羟类固醇脱氢酶 1 型酶(11βHSD1)表达的影响。

方法

72 只雄性 Sprague-Dawley 大鼠随机分为 4 组,每组 18 只:假手术组(Sham)、慢性缩窄性损伤组(CCI)、溶剂对照组(SC)和姜黄素治疗组(Cur100)。姜黄素治疗组(Cur100)于术后第 1 天开始腹腔内给予姜黄素 100mg/kg/天,连续 14 天。在术前 2 天、术后 1、3、5、7、10 和 14 天测量大鼠的足底热缩潜伏期(PTWL)和足底机械缩足阈值(PMWT)。麻醉后取心脏血,分离腰椎(L4、5)脊髓和背根神经节并匀浆。采用酶联免疫吸附试验检测皮质醇变化,免疫化学和 Western blot 检测 11βHSD1 表达变化。

结果

与 Sham 组相比,CCI 组术后 PTWL 和 PMWT 明显下降;血清皮质醇浓度明显升高,CCI 组 11βHSD1 表达明显升高。与 CCI 组相比,Cur100 组 PMWT 和 PTWL 升高,血清皮质醇浓度降低,脊髓和背根神经节 11βHSD1 表达受到抑制。

结论

神经病理性疼痛引起的应激会导致皮质醇释放到血液中,同时 11βHSD1 的表达也会增加。姜黄素可减轻 CCI 引起的热痛觉和机械痛觉过敏,并抑制脊髓和背根神经节中血清皮质醇浓度和 11βHSD1 的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43a0/4108024/9febb05f8e88/40122_2014_24_Fig1_HTML.jpg

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