剖析从喙腹内侧延髓到脊髓三叉神经核双向调节颅面机械敏感性的神经回路

IF 6.7 2区 医学 Q1 NEUROSCIENCES Progress in Neurobiology Pub Date : 2024-01-01 DOI:10.1016/j.pneurobio.2023.102561
Yang Xue, Siyi Mo, Yuan Li, Ye Cao, Xiaoxiang Xu, Qiufei Xie
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引用次数: 0

摘要

慢性颅面痛是一种难治性疾病,其发病机制仍未明确。喙侧脑室内侧髓质(RVM)在下行疼痛促进和抑制中起着至关重要的作用。目前还不清楚从腹侧延髓到脊髓三叉神经核(Sp5)的下行回路是如何组织起来双向调节颅面痛觉的。我们使用病毒追踪、体内光遗传学、钙信号记录和化学遗传学操作来研究 RVM-Sp5 环路的结构和功能。我们发现,投射到Sp5的大多数RVM神经元是GABA能或谷氨酸能神经元,分别促进或抑制颅面痛觉。Sp5的GABA能中间神经元和谷氨酸能投射神经元都接受RVM输入:前者具有抗痛觉作用,而后者具有代痛觉作用。此外,我们还证明,在炎症或功能障碍诱发的咀嚼肌痛觉减退中,接受 RVM 输入的 GABA 能和谷氨酸能 Sp5 神经元都被激活。激活GABA能Sp5神经元或抑制接受RVM投射的谷氨酸能Sp5神经元可逆转咀嚼肌过痛。我们的研究确定了 RVM-Sp5 环路中分别参与促进或抑制颅面痛觉的特定细胞类型和投射。选择性操纵 RVM-Sp5 环路可作为缓解慢性颅面肌肉疼痛的潜在治疗策略。
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Dissecting neural circuits from rostral ventromedial medulla to spinal trigeminal nucleus bidirectionally modulating craniofacial mechanical sensitivity

Chronic craniofacial pain is intractable and its mechanisms remain unclarified. The rostral ventromedial medulla (RVM) plays a crucial role in descending pain facilitation and inhibition. It is unclear how the descending circuits from the RVM to spinal trigeminal nucleus (Sp5) are organized to bidirectionally modulate craniofacial nociception. We used viral tracing, in vivo optogenetics, calcium signaling recording, and chemogenetic manipulations to investigate the structure and function of RVM-Sp5 circuits. We found that most RVM neurons projecting to Sp5 were GABAergic or glutamatergic and facilitated or inhibited craniofacial nociception, respectively. Both GABAergic interneurons and glutamatergic projection neurons in Sp5 received RVM inputs: the former were antinociceptive, whereas the latter were pronociceptive. Furthermore, we demonstrated activation of both GABAergic and glutamatergic Sp5 neurons receiving RVM inputs in inflammation- or dysfunction-induced masseter hyperalgesia. Activating GABAergic Sp5 neurons or inhibiting glutamatergic Sp5 neurons that receive RVM projections reversed masseter hyperalgesia. Our study identifies specific cell types and projections of RVM-Sp5 circuits involved in facilitating or inhibiting craniofacial nociception respectively. Selective manipulation of RVM-Sp5 circuits can be used as potential treatment strategy to relieve chronic craniofacial muscle pain.

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来源期刊
Progress in Neurobiology
Progress in Neurobiology 医学-神经科学
CiteScore
12.80
自引率
1.50%
发文量
107
审稿时长
33 days
期刊介绍: Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.
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