Scholarlink

<p>Spinal glycinergic disinhibition represents an important contributor to mechanical pain hypersensitivity. However, the molecular mechanisms through which peripheral inflammation induces glycinergic disinhibition remain incompletely understood. Here we show that the protein tyrosine phosphatase-1B (PTP1B) is present at inhibitory synapses of spinal somatostatin-positive (SOM<sup>+</sup>) interneurons, a key subpopulation of mechanosensory neurons that conveys nociceptive information. PTP1B directly binds to and dephosphorylates the glycine receptor α1 subunit (GlyR α1). Peripheral inflammation-induced hyperexpression of PTP1B competitively interrupts the interaction of GlyR α1 with GPR39, leading to glycinergic disinhibition, enhanced excitatory output of SOM<sup>+</sup> interneurons, and behavioral hypersensitivity. Pharmacological activation of GPR39, however, could disrupt the PTP1B-GlyR α1 interaction and resume GPR39 binding, resulting in reinstated glycinergic inhibition. Our findings uncover the important role of PTP1B in glycinergic disinhibition following peripheral inflammation and suggest a mechanistic model for dynamic regulation of glycinergic transmission by alternative interactions of GlyR α1 with PTP1B and GPR39.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Enhanced expression of spinal PTP1B contributes to peripheral inflammation- induced glycinergic disinhibition and mechanical pain

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月20日

查看全文
  • Hu-Hu Bai,
  • Xue Bai,
  • Xiao-Xue Liu,
  • Yu-Bo Gao,
  • Juan Li,
  • Xu Yang,
  • Jia-Ning Dang,
  • Ying Wang,
  • Yu-Xuan Zhang,
  • Zhi-Yang Zhang,
  • Qi Zhang,
  • Yan-Ni Liu,
  • Jiang-Ping Liu,
  • Zhan-Wei Suo

摘要

Spinal glycinergic disinhibition represents an important contributor to mechanical pain hypersensitivity. However, the molecular mechanisms through which peripheral inflammation induces glycinergic disinhibition remain incompletely understood. Here we show that the protein tyrosine phosphatase-1B (PTP1B) is present at inhibitory synapses of spinal somatostatin-positive (SOM+) interneurons, a key subpopulation of mechanosensory neurons that conveys nociceptive information. PTP1B directly binds to and dephosphorylates the glycine receptor α1 subunit (GlyR α1). Peripheral inflammation-induced hyperexpression of PTP1B competitively interrupts the interaction of GlyR α1 with GPR39, leading to glycinergic disinhibition, enhanced excitatory output of SOM+ interneurons, and behavioral hypersensitivity. Pharmacological activation of GPR39, however, could disrupt the PTP1B-GlyR α1 interaction and resume GPR39 binding, resulting in reinstated glycinergic inhibition. Our findings uncover the important role of PTP1B in glycinergic disinhibition following peripheral inflammation and suggest a mechanistic model for dynamic regulation of glycinergic transmission by alternative interactions of GlyR α1 with PTP1B and GPR39.