周围神经损伤会导致感觉神经元亚群的偏向性丧失。

IF 5.9 1区 医学 Q1 ANESTHESIOLOGY
PAIN® Pub Date : 2024-12-01 Epub Date: 2024-08-15 DOI:10.1097/j.pain.0000000000003321
Andrew H Cooper, Allison M Barry, Paschalina Chrysostomidou, Romane Lolignier, Jinyi Wang, Magdalena Redondo Canales, Heather F Titterton, David L Bennett, Greg A Weir
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引用次数: 0

摘要

摘要:有大量文献描述了外周轴突切断术后背根神经节(DRG)神经元的丢失,但尚未确定不同亚群的脆弱性。此外,损伤后神经元丢失的程度甚至是否存在最近也受到了质疑。在这项研究中,我们利用一系列转基因重组酶驱动小鼠品系,对分子定义的 DRG 神经元亚群进行基因标记,并追踪它们在创伤性神经损伤后的存活情况。我们发现,幸免于难的神经损伤会导致含有 DRG 容量的细胞明显丢失,同时也会导致小直径 DRG 神经元的丢失。神经元丢失在不同亚群中的发生率不同,在非肽能神经感受器中尤为普遍,以表达 Mrgprd 为标志。我们的研究表明,这一亚群在神经损伤后几乎完全丧失,而在坐骨神经挤压后则严重丧失(约丧失 50%)。最后,我们利用 DRG 神经元存活的体外模型证明,非肽能性痛觉感受器的丢失可能取决于神经营养支持的缺失。总之,这些结果概括了DRG神经元亚群在轴突切断术后的存活程度,对我们了解神经损伤引起的可塑性和疼痛具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Peripheral nerve injury results in a biased loss of sensory neuron subpopulations.

Abstract: There is a rich literature describing the loss of dorsal root ganglion (DRG) neurons following peripheral axotomy, but the vulnerability of discrete subpopulations has not yet been characterised. Furthermore, the extent or even presence of neuron loss following injury has recently been challenged. In this study, we have used a range of transgenic recombinase driver mouse lines to genetically label molecularly defined subpopulations of DRG neurons and track their survival following traumatic nerve injury. We find that spared nerve injury leads to a marked loss of cells containing DRG volume and a concomitant loss of small-diameter DRG neurons. Neuron loss occurs unequally across subpopulations and is particularly prevalent in nonpeptidergic nociceptors, marked by expression of Mrgprd. We show that this subpopulation is almost entirely lost following spared nerve injury and severely depleted (by roughly 50%) following sciatic nerve crush. Finally, we used an in vitro model of DRG neuron survival to demonstrate that nonpeptidergic nociceptor loss is likely dependent on the absence of neurotrophic support. Together, these results profile the extent to which DRG neuron subpopulations can survive axotomy, with implications for our understanding of nerve injury-induced plasticity and pain.

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来源期刊
PAIN®
PAIN® 医学-临床神经学
CiteScore
12.50
自引率
8.10%
发文量
242
审稿时长
9 months
期刊介绍: PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.
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