Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain.
Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain.
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DOI：
10.1097/j.pain.0000000000002677
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发表时间：
2023-01-01
期刊：
影响因子：
7.4
通讯作者：
中科院分区：
文献类型：
--
作者：
文本中提供了补充数字内容。表达胃泌素释放肽受体的脊髓中间神经元与瘙痒有关。这项研究提供的证据表明它们也有助于疼痛机制。浅表背角中表达胃泌素释放肽受体（GRPR）的神经元与脊髓瘙痒通路密切相关。然而，最近的一项研究报告称，其中许多对应于垂直细胞，这是一群被认为传递伤害性信息的中间神经元。在这项研究中，我们使用 GRPRCreERT2 小鼠系来识别和靶向具有 Grpr mRNA 的细胞。我们发现GRPR细胞高度集中在第一层和第二层的外部，它们都是谷氨酸能细胞，占浅表背角兴奋性神经元的~15%。我们之前根据神经肽表达在该区域识别出了 6 个神经化学上不同的兴奋性中间神经元群，GRPR 细胞与这些细胞基本上是分开的，尽管它们与表达 P 物质的细胞有一些重叠。解剖分析表明，GRPR 神经元确实是垂直细胞，它们的轴突相互瞄准，并且在包含投射神经元的区域中呈树状：I 层、外侧脊髓核和 V 层的外侧部分。令人惊讶的是，考虑到 GRPR 细胞在瘙痒中的作用，我们发现大多数细胞接收来自表达 Trpv1（伤害性）传入神经的单突触输入，大多数细胞对有害和瘙痒性刺激做出反应，并且化学遗传学激活它们会导致与疼痛相关和瘙痒相关的行为。总之，这些发现表明 GRPR 细胞参与了导致疼痛和瘙痒的脊髓回路。
Supplemental Digital Content is Available in the Text. Gastrin-releasing peptide receptor–expressing spinal interneurons have been implicated in itch. This study provides evidence that they also contribute to pain mechanisms. Neurons in the superficial dorsal horn that express the gastrin-releasing peptide receptor (GRPR) are strongly implicated in spinal itch pathways. However, a recent study reported that many of these correspond to vertical cells, a population of interneurons that are believed to transmit nociceptive information. In this study, we have used a GRPRCreERT2 mouse line to identify and target cells that possess Grpr mRNA. We find that the GRPR cells are highly concentrated in lamina I and the outer part of lamina II, that they are all glutamatergic, and that they account for ∼15% of the excitatory neurons in the superficial dorsal horn. We had previously identified 6 neurochemically distinct excitatory interneuron populations in this region based on neuropeptide expression and the GRPR cells are largely separate from these, although they show some overlap with cells that express substance P. Anatomical analysis revealed that the GRPR neurons are indeed vertical cells, and that their axons target each other, as well as arborising in regions that contain projection neurons: lamina I, the lateral spinal nucleus, and the lateral part of lamina V. Surprisingly, given the proposed role of GRPR cells in itch, we found that most of the cells received monosynaptic input from Trpv1-expressing (nociceptive) afferents, that the majority responded to noxious and pruritic stimuli, and that chemogenetically activating them resulted in pain-related and itch-related behaviours. Together, these findings suggest that the GRPR cells are involved in spinal cord circuits that underlie both pain and itch.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
DOI：
10.1113/jp275240
发表时间：
2018-05-01
期刊：
The Journal of physiology
影响因子：
--
作者：
Balachandar A;Prescott SA
通讯作者：
Prescott SA
影响因子：
7.4
作者：
Aresh B;Freitag FB;Perry S;Blümel E;Lau J;Franck MCM;Lagerström MC
通讯作者：
Lagerström MC
影响因子：
48
作者：
Cai D;Cohen KB;Luo T;Lichtman JW;Sanes JR
通讯作者：
Sanes JR
影响因子：
5.5
作者：
Grudt, TJ;Perl, ER
通讯作者：
Perl, ER