Convergence of peptidergic and non-peptidergic protein markers in the human dorsal root ganglion and spinal dorsal horn.
Convergence of peptidergic and non-peptidergic protein markers in the human dorsal root ganglion and spinal dorsal horn.
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DOI：
10.1002/cne.25122
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发表时间：
2021-07-01
期刊：
影响因子：
--
通讯作者：
Price TJ
中科院分区：
文献类型：
--
作者：
Shiers SI;Sankaranarayanan I;Jeevakumar V;Cervantes A;Reese JC;Price TJ
外周感觉神经元的特征在于它们的大小、分子特征和对特定刺激的生理反应。在小鼠中，肽能和非肽能伤害感受器的亚群是不同的，并支配脊髓背角的不同层。这些神经元的独特分子特征和神经解剖学组织支持某些类型的伤害性刺激的标记线理论。然而，长期存在的证据支持许多物种中伤害感受器的多模态性质。我们最近发现，肽能标记物，CGRP，和非肽能标记物，P2 X3 R，在人背根神经节（DRG）的mRNA水平上表现出很大程度上重叠的表达。在此，我们的目的是评估伤害感受器标记物的蛋白质分布，包括其在人DRG和脊髓中的中央投射。使用从器官供体获得的DRG，我们观察到CGRP和P2 X3 R由约33%的人DRG神经元共表达，TrpV 1在约60%的人DRG神经元中表达。在脊髓背侧，CGRP、P2 X3 R、TrpV 1和Nav1.7蛋白染色整个1-2层，仅P2 XR 3显示表达梯度。通过使用苏木精和伊红染色相邻切片测量胶状质的大小来证实这一点。我们的研究结果与已知的大多数灵长类动物伤害感受器的多模态性质一致，并表明小鼠和人类之间的伤害感受器的中枢投射模式是不同的。阐明人类伤害感受器如何连接到背角神经元的子集将是重要的，了解这些物种差异的生理后果。
Peripheral sensory neurons are characterized by their size, molecular profiles, and physiological responses to specific stimuli. In mouse, the peptidergic and non-peptidergic subsets of nociceptors are distinct and innervate different lamina of the spinal dorsal horn. The unique molecular signature and neuroanatomical organization of these neurons supports a labeled line theory for certain types of nociceptive stimuli. However, long standing evidence supports the polymodal nature of nociceptors in many species. We have recently shown that the peptidergic marker, CGRP, and the non-peptidergic marker, P2X3R, show largely overlapping expression at the mRNA level in human dorsal root ganglion (DRG). Herein, our aim was to assess the protein distribution of nociceptor markers, including their central projections, in the human DRG and spinal cord. Using DRGs obtained from organ donors, we observed that CGRP and P2X3R were co-expressed by approximately 33% of human DRG neurons and TrpV1 was expressed in ~60% of human DRG neurons. In the dorsal spinal cord, CGRP, P2X3R, TrpV1 and Nav1.7 protein stained the entirety of lamina 1–2, with only P2XR3 showing a gradient of expression. This was confirmed by measuring the size of the substantia gelatinosa using Hematoxylin and Eosin staining of adjacent sections. Our findings are consistent with the known polymodal nature of most primate nociceptors and indicate that the central projection patterns of nociceptors are different between mice and humans. Elucidating how human nociceptors connect to subsets of dorsal horn neurons will be important for understanding the physiological consequences of these species differences.
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