Red nucleus mGluR2 but not mGluR3 mediates inhibitory effect in the development of SNI-induced neuropathological pain by suppressing the expressions of TNF-α and IL-1β

IF 4.4 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Neurochemistry international Pub Date : 2024-08-22 DOI:10.1016/j.neuint.2024.105840
Wen-Tao Wang , Fan Feng , Miao-Miao Zhang , Xue Tian , Qing-Qing Yang , Yue-Jia Li , Xiao-Xia Tao , Ya-Li Xu , E Dou , Jun-Yang Wang , Xiao-Yan Zeng
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引用次数: 0

Abstract

Our previous study has verified that activation of group Ⅰ metabotropic glutamate receptors (mGluRⅠ) in the red nucleus (RN) facilitate the development of neuropathological pain. Here, we further discussed the functions and possible molecular mechanisms of red nucleus mGluR Ⅱ (mGluR2 and mGluR3) in the development of neuropathological pain induced by spared nerve injury (SNI). Our results showed that mGluR2 and mGluR3 both were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the protein expression of mGluR2 rather than mGluR3 was significantly reduced in the RN contralateral to the nerve lesion. Injection of mGluR2/3 agonist LY379268 into the RN contralateral to the nerve injury at 2 weeks post-SNI significantly attenuated SNI-induced neuropathological pain, this effect was reversed by mGluR2/3 antagonist EGLU instead of selective mGluR3 antagonist β-NAAG. Intrarubral injection of LY379268 did not alter the PWT of contralateral hindpaw in normal rats, while intrarubral injection of EGLU rather than β-NAAG provoked a significant mechanical allodynia. Further studies indicated that the expressions of nociceptive factors TNF-α and IL-1β in the RN were enhanced at 2 weeks post-SNI. Intrarubral injection of LY379268 at 2 weeks post-SNI significantly suppressed the overexpressions of TNF-α and IL-1β, these effects were reversed by EGLU instead of β-NAAG. Intrarubral injection of LY379268 did not influence the protein expressions of TNF-α and IL-1β in normal rats, while intrarubral injection of EGLU rather than β-NAAG significantly boosted the expressions of TNF-α and IL-1β. These findings suggest that red nucleus mGluR2 but not mGluR3 mediates inhibitory effect in the development of SNI-induced neuropathological pain by suppressing the expressions of TNF-α and IL-1β. mGluR Ⅱ may be potential targets for drug development and clinical treatment of neuropathological pain.

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红核 mGluR2 而非 mGluR3 通过抑制 TNF-α 和 IL-1β 的表达,在 SNI 诱导的神经病理性疼痛的发展过程中起介导抑制作用。
我们之前的研究已经证实,红核(RN)中Ⅰ群代谢谷氨酸受体(mGluRⅠ)的激活促进了神经病理性疼痛的发生。在此,我们进一步探讨了红核mGluRⅡ(mGluR2和mGluR3)在幸免神经损伤(SNI)诱导的神经病理性疼痛发生中的功能和可能的分子机制。我们的研究结果表明,mGluR2 和 mGluR3 在正常大鼠的 RN 中均呈组成型表达。在神经损伤后 2 周,mGluR2 而不是 mGluR3 的蛋白表达在神经损伤对侧的 RN 中明显减少。在SNI后2周,向神经损伤对侧RN注射mGluR2/3激动剂LY379268可明显减轻SNI诱导的神经病理性疼痛,而mGluR2/3拮抗剂EGLU代替选择性mGluR3拮抗剂β-NAAG可逆转这种效应。在正常大鼠的后爪内注射 LY379268 不会改变对侧后爪的脉搏波速度,而在大鼠的后爪内注射 EGLU 而不是 β-NAAG 会引起明显的机械异感。进一步的研究表明,SNI 后 2 周,RN 中痛觉因子 TNF-α 和 IL-1β 的表达增强。在 SNI 后 2 周,睾丸内注射 LY379268 能显著抑制 TNF-α 和 IL-1β 的过度表达,而 EGLU 代替 β-NAAG 则能逆转这些效应。正常大鼠睾丸内注射 LY379268 不会影响 TNF-α 和 IL-1β 的蛋白表达,而睾丸内注射 EGLU 而非 β-NAAG 则会明显提高 TNF-α 和 IL-1β 的表达。这些研究结果表明,红核mGluR2而非mGluR3通过抑制TNF-α和IL-1β的表达来介导抑制SNI诱导的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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