Yu Hongwei, Shin Seung Min, Wang Fei, Xu Hao, Xiang Hongfei, Cai Yongsong, Itson-Zoske Brandon, Hogan Quinn H
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA.
Pain Rep. 2018 Dec 26;4(1):e703. doi: 10.1097/PR9.0000000000000703. eCollection 2019 Jan-Feb.
Tmem100 modulates interactions between TRPA1 and TRPV1. The cell specificity of Tmem100 expression in dorsal root ganglia (DRGs) is not well defined, nor is the effect of peripheral nerve injury on Tmem100 expression.
This study was designed to determine the cell specificity of Tmem100 expression in DRG and its subcellular localization, and to examine how Tmem100 expression may be altered in painful conditions.
Dorsal root ganglion Tmem100 expression was determined by immunohistochemistry, immunoblot, and quantitative real-time PCR, and compared between various experimental rat pain models and controls.
Tmem100 is expressed in both neurons and perineuronal glial cells in the rat DRG. The plasma membrane and intracellular localization of Tmem100 are identified in 83% ± 6% of IB4-positive and 48% ± 6% of calcitonin gene-related peptide-positive neurons, as well as in medium- and large-sized neurons, with its immunopositivity colocalized to TRPV1 (94% ± 5%) and TRPA1 (96% ± 3%). Tmem100 is also detected in the perineuronal satellite glial cells and in some microglia. Tmem100 protein is significantly increased in the lumbar DRGs in the complete Freund adjuvant inflammatory pain. By contrast, peripheral nerve injury by spinal nerve ligation diminishes Tmem100 expression in the injured DRG, with immunoblot and immunohistochemistry experiments showing reduced Tmem100 protein levels in both neurons and satellite glial cells of DRGs proximal to injury, whereas Tmem100 is unchanged in adjacent DRGs. The spared nerve injury model also reduces Tmem100 protein in the injured DRGs.
Our data demonstrate a pain pathology-dependent alteration of DRG Tmem100 protein expression, upregulated during CFA inflammatory pain but downregulated during neuropathic pain.
Tmem100调节TRPA1和TRPV1之间的相互作用。背根神经节（DRG）中Tmem100表达的细胞特异性尚未明确界定，周围神经损伤对Tmem100表达的影响也不清楚。
本研究旨在确定Tmem100在DRG中的细胞特异性及其亚细胞定位，并研究在疼痛状态下Tmem100表达如何变化。
通过免疫组织化学、免疫印迹和定量实时PCR测定背根神经节Tmem100表达，并在各种实验性大鼠疼痛模型和对照之间进行比较。
Tmem100在大鼠DRG的神经元和神经元周围神经胶质细胞中均有表达。在83%±6%的IB4阳性神经元和48%±6%的降钙素基因相关肽阳性神经元以及中大型神经元中鉴定出Tmem100的质膜和细胞内定位，其免疫阳性与TRPV1（94%±5%）和TRPA1（96%±3%）共定位。在神经元周围卫星神经胶质细胞和一些小胶质细胞中也检测到Tmem100。在完全弗氏佐剂炎性疼痛中，腰段DRG中Tmem100蛋白显著增加。相比之下，脊神经结扎造成的周围神经损伤会降低损伤DRG中Tmem100的表达，免疫印迹和免疫组织化学实验显示，损伤近端DRG的神经元和卫星神经胶质细胞中Tmem100蛋白水平均降低，而相邻DRG中的Tmem100则无变化。保留神经损伤模型也会降低损伤DRG中的Tmem100蛋白。
我们的数据表明，DRG中Tmem100蛋白表达存在疼痛病理依赖性改变，在CFA炎性疼痛期间上调，但在神经性疼痛期间下调。
