mRNA Expression of Mineralocorticoid and Glucocorticoid Receptors in Human and Mouse Sensory Neurons of the Dorsal Root Ganglia.

IF 4.6 2区医学 Q1 ANESTHESIOLOGY

Anesthesia and analgesia Pub Date : 2025-05-01 DOI:10.1213/ANE.0000000000007133

Katherine A Qualls, Feni K Kadakia, Elizabeth K Serafin, Debora De Nardin Lückemeyer, Steve Davidson, Judith A Strong, Jun-Ming Zhang

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Abstract

Background: Corticosteroid receptors, including mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), play important roles in inflammatory pain in the dorsal root ganglion (DRG). Although it is widely known that activating the GR reduces inflammatory pain, it has recently been shown that MR activation contributes to pain and neuronal excitability in rodent studies. Moreover, little is known about the translation of this work to humans, or the mechanisms through which corticosteroid receptors regulate inflammatory pain.

Methods: Corticosteroid receptor expression in human and mouse DRGs was characterized. RNAscope was used to perform high-resolution in situ hybridization for GR and MR mRNAs and to examine their colocalization with markers for nociceptors ( SCN10A , Na V 1.8 mRNA) and Aβ mechanoreceptors ( KCNS1 , Kv9.1 mRNA) in human DRG and C57BL/6J mouse DRG samples.

Results: GR and MR mRNAs are expressed in almost all DRG neurons across species. The 2 receptors colocalize in 99.2% of human DRG neurons and 95.9% of mouse DRG neurons ( P = .0004, Fisher exact test). In both human and mouse DRGs, the large-diameter KCNS1+ Aβ mechanoreceptors showed a significantly higher MR/GR ratio (MR-leaning) compared to KCNS1- neurons (human: 0.23 vs 0.04, P = .0002; mouse: 0.35 vs -0.24, P < .0001; log ratios, unpaired t test), whereas small-diameter SCN10A+ nociceptive neurons showed a significantly lower MR/GR ratio (GR-leaning) compared to SCN10A- neurons (human: -0.02 vs 0.18, P = .0001; mouse: -0.16 vs 0.08, P < .0001; log ratios, unpaired t test).

Conclusions: These findings indicate that mouse corticosteroid receptor mRNA expression reflects human expression in the DRG, and that mice could be a suitable model for studying corticosteroid receptor involvement in pain. Additionally, this study supports the translatability of rodent data to humans for the use of more selective corticosteroids at the DRG in pain treatments.

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人和小鼠背根神经节感觉神经元中糖皮质激素和矿化皮质激素受体mRNA的表达。

背景：皮质类固醇受体，包括矿物皮质激素受体（MR）和糖皮质激素受体（GR），在背根神经节（DRG）炎症性疼痛中起重要作用。虽然众所周知，激活GR可以减轻炎症性疼痛，但最近在啮齿动物研究中表明，MR激活有助于疼痛和神经元兴奋性。此外，对于这项工作在人类身上的转化，或者皮质类固醇受体调节炎症性疼痛的机制，我们知之甚少。方法：研究皮质类固醇受体在人和小鼠DRGs中的表达。使用RNAscope对GR和MR mRNA进行高分辨率原位杂交，并检测它们与人类DRG和C57BL/6J小鼠DRG样品中伤害感受器（SCN10A, NaV1.8 mRNA）和Aβ机械感受器（KCNS1, Kv9.1 mRNA）标记物的共定位。结果：GR和MR mrna在几乎所有的DRG神经元中均有表达。这两种受体共定位于99.2%的人类DRG神经元和95.9%的小鼠DRG神经元（P = 0.0004， Fisher精确检验）。在人和小鼠DRGs中，与KCNS1-神经元相比，大直径KCNS1+ a β机械受体的MR/GR比（MR-leaning）显著提高(人：0.23 vs 0.04, P = 0.0002；小鼠：0.35 vs -0.24, P < 0.0001；对数比，未配对t检验)，而小直径SCN10A+伤害性神经元的MR/GR比（GR倾向）明显低于SCN10A-神经元(人：-0.02 vs 0.18, P = 0.0001；小鼠：-0.16 vs 0.08, P < 0.0001；对数比，非配对t检验)。结论：小鼠皮质类固醇受体mRNA在DRG中的表达反映了人类的表达，小鼠可以作为研究皮质类固醇受体参与疼痛的合适模型。此外，本研究支持啮齿动物数据可翻译为人类在DRG疼痛治疗中使用更具选择性的皮质类固醇。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anesthesia and analgesia 医学-麻醉学

CiteScore

9.90

自引率

7.00%

发文量

817

审稿时长

2 months

期刊介绍： Anesthesia & Analgesia exists for the benefit of patients under the care of health care professionals engaged in the disciplines broadly related to anesthesiology, perioperative medicine, critical care medicine, and pain medicine. The Journal furthers the care of these patients by reporting the fundamental advances in the science of these clinical disciplines and by documenting the clinical, laboratory, and administrative advances that guide therapy. Anesthesia & Analgesia seeks a balance between definitive clinical and management investigations and outstanding basic scientific reports. The Journal welcomes original manuscripts containing rigorous design and analysis, even if unusual in their approach.