Scholarlink

<p>Pain transmission is considered a unilateral process; however, development of bilateral hyperalgesia, including mirror-image pain (MIP), challenges this notion. The neural basis underlying bilateral hyperalgesia remains unclear. We investigated whether microglial activation within the corpus callosum is associated with interhemispheric propagation of inflammatory responses contributing to MIP. In a photothrombotic reperfusion mouse model, lysophosphatidic acid (LPA) signalling was associated with microglial activation in the contralateral corpus callosum and MIP development. Furthermore, PF8380 or minocycline suppressed bilateral hyperalgesia with MIP, supporting the therapeutic relevance of targeting LPA signalling and microglial activation. Together, these data support a model of an inflammatory circuit involving ischemic-core LPA, callosal microglia, contralateral insular PGE₂ signalling, and contralateral ACC activation that contribute to MIP. Because dysregulated LPA signalling and microglial activation are features of other neuroinflammatory conditions, transcallosal glial crosstalk may also contribute to widespread pain syndromes. Our findings highlight the therapeutic potential of targeting LPA-related pathways.</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

Lysophosphatidic acid drives to mirror-image pain via corpus callosum-mediated propagation of inflammatory responses

  • 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
  • Hiroyuki Neyama,
  • Ryoma Kizu,
  • Rae Maeda,
  • Hiroshi Ueda,
  • Yuki Sugiura

摘要

Pain transmission is considered a unilateral process; however, development of bilateral hyperalgesia, including mirror-image pain (MIP), challenges this notion. The neural basis underlying bilateral hyperalgesia remains unclear. We investigated whether microglial activation within the corpus callosum is associated with interhemispheric propagation of inflammatory responses contributing to MIP. In a photothrombotic reperfusion mouse model, lysophosphatidic acid (LPA) signalling was associated with microglial activation in the contralateral corpus callosum and MIP development. Furthermore, PF8380 or minocycline suppressed bilateral hyperalgesia with MIP, supporting the therapeutic relevance of targeting LPA signalling and microglial activation. Together, these data support a model of an inflammatory circuit involving ischemic-core LPA, callosal microglia, contralateral insular PGE₂ signalling, and contralateral ACC activation that contribute to MIP. Because dysregulated LPA signalling and microglial activation are features of other neuroinflammatory conditions, transcallosal glial crosstalk may also contribute to widespread pain syndromes. Our findings highlight the therapeutic potential of targeting LPA-related pathways.