2. Academic Validation
  3. Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β

Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β

  • Neuropharmacology. 2025 Jun 15:271:110387. doi: 10.1016/j.neuropharm.2025.110387.
Ya-Li Xu 1,  Yu-Tong Xia 2,  Miao-Miao Zhang 2,  Yue-Jia Li 2,  Xiao-Xia Tao 2,  Ke Li 2,  Qing-Qing Yang 3,  Xue Tian 2,  Ji-Bo Wu 4,  Ya-Ting Shi 2,  Jun-Yang Wang 5,  Xiao-Yan Zeng 6
Affiliations

Affiliations

  • 1 Department of Blood Transfusion, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • 2 Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.
  • 3 Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China; Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China.
  • 4 Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China; Department of Blood Transfusion, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
  • 5 Department of Pathogenic Biology and Immunology, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China. Electronic address: jywang@mail.xjtu.edu.cn.
  • 6 Department of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China. Electronic address: xiaoyanzeng@mail.xjtu.edu.cn.
PMID: 40010564 DOI: 10.1016/j.neuropharm.2025.110387
Abstract

Metabotropic Glutamate Receptors (mGluR) participate in pain modulation and mediate different effects in nociceptive stimuli, relying on the receptor subtype activated and its anatomical location. Here, we addressed the functions of mGluR Ⅲ group (mGluR4, mGluR6, mGluR7, and mGluR8) in the red nucleus (RN) in nociception and the development of neuropathic pain induced by spared nerve injury (SNI) using male rats. Our results showed that mGluR4, mGluR7, and mGluR8, except for mGluR6, were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the expressions of mGluR4 and mGluR8 rather than mGluR7 were reduced in the RN contralateral to the nerve lesion. Unilateral administration of mGluR Ⅲ antagonist MSOP to the RN of normal rats decreased the PWT of contralateral hindpaw and evoked pronounced mechanical allodynia, which was blocked by mGluR4 Agonist VU0155041 or mGluR8 Agonist AZ12216052 instead of mGluR7 Agonist AMN082. Moreover, administration of VU0155041 or AZ12216052 to the RN contralateral to the nerve injury at 2 weeks post-SNI alleviated SNI-induced neuropathic pain. Further studies indicated that administration of MSOP to the RN of normal rats increased the expressions of nociceptive factors TNF-α and IL-1β, which were blocked by VU0155041 or AZ12216052 instead of AMN082. Additionally, administration of VU0155041 or AZ12216052 to the RN at 2 weeks post-SNI inhibited the overexpressions of TNF-α and IL-1β induced by SNI. These findings suggest that red nucleus mGluR4 and mGluR8 instead of mGluR7 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β.

Keywords

Interleukin-1β; Metabotropic glutamate receptors; Neuropathic pain; Red nucleus; Tumor necrosis factor-α.

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