Okuda Takao, Uchiyama Sawako, Sato Naoko, Sugimura Yae K, Takahashi Yukari, Tsuda Makoto, Kato Fusao
Department of Neuroscience, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan.
Center for Neuroscience of Pain, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan.
iScience. 2025 Jun 25;28(8):113001. doi: 10.1016/j.isci.2025.113001. eCollection 2025 Aug 15.
Projections from the external lateral parabrachial nucleus (elPB) to the central amygdala (CeA) are a key pathway for nociceptive signals and play a crucial role in establishing nociplastic pain sensitization, a state of heightened pain without nociceptor activation or nerve injury. To investigate their roles in nociplastic pain, we aimed to analyze how pain-activated elPB neurons transmit information to pain-activated CeA neurons. Using transgenic TRAP2 mice that underwent transient localized inflammation, we selectively expressed marker proteins, light-sensitive channels, and chemogenetic receptors in pain-activated neurons. We found that the pain-activated ("nociTRAPed") neurons in the elPB project extensively to the CeA, particularly to the caudal half of the capsular CeA (defined as "posterior CeC" or pCeC), where they form robust functional connections with nociTRAPed pCeC neurons, promoting nociplastic sensitization. We propose that the pCeC serves as the site of direct co-activation with pain-activated elPB neurons, translating peripheral nociceptive information into CeA excitation.
从外侧臂旁核外部（elPB）到中央杏仁核（CeA）的投射是伤害性信号的关键通路，在建立伤害性可塑性疼痛敏化过程中起关键作用，伤害性可塑性疼痛敏化是一种在无伤害感受器激活或神经损伤情况下疼痛增强的状态。为了研究它们在伤害性可塑性疼痛中的作用，我们旨在分析疼痛激活的elPB神经元如何将信息传递给疼痛激活的CeA神经元。使用经历短暂局部炎症的转基因TRAP2小鼠，我们在疼痛激活的神经元中选择性表达标记蛋白、光敏感通道和化学遗传受体。我们发现，elPB中疼痛激活的（“nociTRAPed”）神经元广泛投射到CeA，特别是投射到被膜CeA的后半部分（定义为“后CeC”或pCeC），在那里它们与nociTRAPed pCeC神经元形成强大的功能连接，促进伤害性可塑性敏化。我们提出，pCeC作为与疼痛激活的elPB神经元直接共同激活的位点，将外周伤害性信息转化为CeA兴奋。
