Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1β

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-06-04 DOI:10.1016/j.neuint.2024.105786
Xue Tian , Wen-Tao Wang , Miao-Miao Zhang , Qing-Qing Yang , Ya-Li Xu , Ji-Bo Wu , Xin-Xin Xie , Jun-Yang Wang , Jing-Yuan Wang
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Abstract

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1β in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1β. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1β, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1β. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

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红核 mGluR1 和 mGluR5 通过刺激 TNF-α 和 IL-1β 的表达促进神经病理性疼痛的发展
我们之前的研究发现,红核(RN)中的谷氨酸通过代谢型谷氨酸受体(mGluR)促进神经病理性疼痛的发生。在此,我们进一步探讨了红核 mGluR Ⅰ(mGluR1 和 mGluR5)在幸免神经损伤(SNI)诱导的神经病理性疼痛发生过程中的作用和可能的分子机制。我们的数据表明,mGluR1 和 mGluR5 在正常大鼠的 RN 中均呈组成型表达。SNI两周后,mGluR1和mGluR5在神经损伤对侧RN中的表达明显增加。在 SNI 两周后,向神经损伤对侧 RN 施用 mGluR1 拮抗剂 LY367385 或 mGluR5 拮抗剂 MTEP 可明显改善 SNI 引起的神经病理性疼痛。然而,对正常大鼠的 RN 单侧施用 mGluRⅠ 激动剂 DHPG 会引起明显的机械异感,LY367385 或 MTEP 可阻断这种效应。进一步的研究表明,SNI 后 2 周时,RN 中 TNF-α 和 IL-1β 的表达也升高。在 SNI 后 2 周给 RN 注射 mGluR1 拮抗剂 LY367385 或 mGluR5 拮抗剂 MTEP 可显著抑制 TNF-α 和 IL-1β 的升高。然而,给正常大鼠的 RN 施用 mGluR Ⅰ 激动剂 DHPG 会显著增强 TNF-α 和 IL-1β 的表达,LY367385 或 MTEP 可阻断这些效应。这些结果表明,激活红核 mGluR1 和 mGluR5 可刺激 TNF-α 和 IL-1β 的表达,从而促进神经病理性疼痛的发生。
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来源期刊
Neurochemistry international
Neurochemistry international 医学-神经科学
CiteScore
8.40
自引率
2.40%
发文量
128
审稿时长
37 days
期刊介绍: Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.
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