坐骨神经慢性压迫损伤诱导的神经性疼痛过程中N-甲基-D-天冬氨酸受体与抗坏血酸之间的功能相互作用

Functional interaction between N-methyl-D-aspartate receptor and ascorbic acid during neuropathic pain induced by chronic constriction injury of the sciatic nerve.

作者信息

Saffarpour Sepideh, Nasirinezhad Farinaz

机构信息

出版信息

J Basic Clin Physiol Pharmacol. 2017 Nov 27;28(6):601-608. doi: 10.1515/jbcpp-2017-0015.

DOI:10.1515/jbcpp-2017-0015

PMID:28902622

Abstract

BACKGROUND

Neuropathic pain is a chronic pain condition, which is resistant to therapy. Ascorbate was released because of the activation of glutaminergic neurons. Due to the important role of N-methyl-D-aspartate (NMDA) receptors in the pathophysiology of neuropathic pain, this study investigated the analgesic efficacy of ascorbic acid (AA) in neuropathic pain condition and the role of NMDA receptors in this effect.

METHODS

For this purpose, adult male rats were randomly allocated to experimental groups (n=8 in each group). Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve. During the second week after CCI, animals received a single injection of 1, 3, 5, or 10 mg/kg of AA intraperitoneally and pain threshold was determined 15 and 60 min later. The antinociceptive effect of chronic administration was also evaluated by intraperitoneal injection (IP) of 3 mg/kg AA for 3 weeks. To determine the role of NMDA receptors, separate groups of animals 30 min after single injection of AA (1 mg/kg) animals received i.p. injection of ketamine (5 mg/kg), MK-801 (0.01 mg/kg), or glutamate (1000 nmol) and were tested 20 min afterwards. Data analyzed by ANOVA and Newman-Keuls tests and p<0.05 were considered as significant.

RESULTS

IP of 3, 5 and 10 mg/kg increased the pain threshold during the second week after CCI (p<0.05, F=3 in tactile allodynia and p<0.01, F=3.2 in thermal and mechanical hyperalgeisa). Chronic administration of AA also produced antinociceptive effect. Ascorbic acid (1 mg/kg, i.p.) inhibited MK-801 and ketamine-induced antinociception response significantly (p<0.001, F=2). It also prevented the analgesic effect of glutamate administration (p<0.001, F=2).

CONCLUSIONS

The results indicated that AA produced a dose-dependent antinociceptive effect that seems to mediate through its interaction with NMDA receptors.

摘要

背景

神经性疼痛是一种慢性疼痛病症，对治疗具有抗性。由于谷氨酰胺能神经元的激活而释放出抗坏血酸盐。鉴于N-甲基-D-天冬氨酸（NMDA）受体在神经性疼痛的病理生理学中具有重要作用，本研究调查了抗坏血酸（AA）在神经性疼痛病症中的镇痛效果以及NMDA受体在该作用中的角色。

方法

为此，将成年雄性大鼠随机分配至各实验组（每组n = 8）。通过坐骨神经慢性压迫损伤（CCI）诱导神经性疼痛。在CCI后的第二周，动物腹腔注射1、3、5或10 mg/kg的AA单次剂量，并在15和60分钟后测定疼痛阈值。还通过腹腔注射（IP）3 mg/kg AA持续3周来评估慢性给药的镇痛效果。为确定NMDA受体的作用，在单次注射AA（1 mg/kg）30分钟后，将动物分组，分别腹腔注射氯胺酮（5 mg/kg）、MK-801（0.01 mg/kg）或谷氨酸盐（1000 nmol），并在20分钟后进行测试。数据通过方差分析和纽曼-基尔斯检验进行分析，p<0.05被视为具有显著性。

结果

腹腔注射3、5和10 mg/kg可提高CCI后第二周的疼痛阈值（触觉异常性疼痛中p<0.05，F = 3；热痛觉过敏和机械性痛觉过敏中p<0.01，F = 3.2）。AA的慢性给药也产生了镇痛效果。抗坏血酸（1 mg/kg，腹腔注射）显著抑制了MK-801和氯胺酮诱导的镇痛反应（p<0.001，F = 2）。它还阻止了谷氨酸盐给药的镇痛效果（p<0.001，F = 2）。