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口服 L-苏糖酸镁通过抑制神经炎症依赖性大鼠中枢敏化缓解根性疼痛。

Oral application of magnesium-L-threonate alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats.

机构信息

Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.

Department of Anesthesiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China.

出版信息

Brain Res. 2024 Sep 15;1839:148910. doi: 10.1016/j.brainres.2024.148910. Epub 2024 Apr 9.

DOI:10.1016/j.brainres.2024.148910

PMID:38604557

Abstract

BACKGROUND

We have reported neuro-inflammation is involved in radicular pain by enhancing the efficiency of pain synaptic transmission in spinal level. Recently, peers' studies have confirmed that magnesium deficiency leads to neuro-inflammation, thus contributes to memory and emotional deficits and pain hypersensitivity in antineoplastic agents treated rats. In this study, we explore the effect of oral application of magnesium-L-threonate (L-TAMS) in radicular pain induced by lumbar disc herniation (LDH) of rats and the possible mechanisms.

METHODS

Rat model of LDH was induced by autologous nucleus pulposus (NP) implantation. Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. L-TAMS was applied from drinking water at dosage of 604 mg/kg/day from 2 day before NP implantation and until the end of the experiment. Free Mg content in serum and cerebrospinal fluid (CSF) was measured by calmagite chromometry. Synaptic transmission efficiency was determined by C-fiber evoked field potentials recorded by electrophysiologic recording in vivo. The activation of microglia in spinal dorsal horn was displayed by immunofluorescence staining and western blotting. The expressions of pro-inflammatory cytokines and glutamic N-methyl-D-aspartate receptor (NMDAR) subunits (NR2A, NR2B) were assessed by western blotting and enzyme-linked immunosorbent assay (ELISA) respectively.

RESULTS

NP implantation induced mechanical allodynia and thermal hyperalgesia, accompanied by decreased Mg concentration in serum and CSF which were both obscured by oral application of L-TAMS. L-TAMS inhibited spinal microglia activation and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) expression of rats with NP. L-TAMS decreased C-fiber evoked potentials and NR2B protein level in rats with NP, which were rescued by extra intrathecal delivery of TNF-α or IL-6 or IL-1β.

CONCLUSIONS

Oral application of L-TAMS alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats.

摘要

背景

我们曾报道过神经炎症通过增强脊髓水平疼痛突触传递效率而参与根性疼痛。最近，同行的研究已经证实，镁缺乏会导致神经炎症，从而导致抗肿瘤药物治疗的大鼠出现记忆和情绪缺陷以及疼痛过敏。在这项研究中，我们探讨了口服镁-L-苏氨酸（L-TAMS）对大鼠腰椎间盘突出症（LDH）引起的根性疼痛的影响及其可能的机制。

方法

通过自体髓核植入诱导大鼠 LDH 模型。通过 von Frey 纤维和热板试验分别评估机械和热痛阈值。L-TAMS 从 NP 植入前 2 天开始通过饮用水给药，剂量为 604mg/kg/天，直至实验结束。血清和脑脊液（CSF）中的游离镁含量用钙镁试剂比色法测定。通过电生理记录体内记录的 C 纤维诱发的场电位来确定突触传递效率。免疫荧光染色和 Western blot 显示脊髓背角小胶质细胞的激活。通过 Western blot 和酶联免疫吸附试验（ELISA）分别评估促炎细胞因子和谷氨酸 N-甲基-D-天冬氨酸受体（NMDAR）亚基（NR2A、NR2B）的表达。

结果

NP 植入引起机械性痛觉过敏和热痛觉过敏，同时伴有血清和 CSF 中镁浓度降低，这些均被口服 L-TAMS 掩盖。L-TAMS 抑制 NP 大鼠脊髓小胶质细胞激活和促炎细胞因子（TNF-α、IL-6、IL-1β）表达。L-TAMS 降低 NP 大鼠 C 纤维诱发的电位和 NR2B 蛋白水平，而 TNF-α、IL-6 或 IL-1β 的鞘内额外给药可挽救这一作用。