Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
PLoS One. 2018 Jun 21;13(6):e0199512. doi: 10.1371/journal.pone.0199512. eCollection 2018.
In this study, we investigated temporal changes in galanin receptor type 2 (GalR2) expression in NF200-, galanin-, neuropeptide Y (NPY)-, and neuronal nitric oxide synthase (nNOS)-like immunoreactive (LI) dorsal root ganglion (DRG) neurons after median nerve chronic constriction injury (CCI), and the effects of GalR2 on c-Fos expression in the cuneate nucleus (CN). Double immunofluorescence labeling methods were used to appraise changes in GalR2 expression in NF200-LI, galanin-LI, NPY-LI, and nNOS-LI DRG neurons after CCI. The von Frey assay was used to assess the efficiency of intraplantar administration of saline, M871 (a GalR2 antagonist), or AR-M1896 (a GalR2 agonist) on neuropathic signs of rats with CCI. The effects of alterations in c-Fos expression were assessed in all treatments. The percentage of GalR2-LI neurons in lesioned DRGs increased and peaked at 1 week after CCI. We further detected that percentages of GalR2-LI neurons labeled for NF200, galanin, NPY, and nNOS significantly increased following CCI. Furthermore, M871 remarkably attenuated tactile allodynia, but the sensation was slightly aggravated by AR-M1896 after CCI. Consequentially, after electrical stimulation of the CCI-treated median nerve, the number of c-Fos-LI neurons in the cuneate nucleus (CN) was significantly reduced in the M871 group, whereas it increased in the AR-M1896 group. These results suggest that activation of GalR2, probably through NPY or nitric oxide, induces c-Fos expression in the CN and transmits mechanical allodynia sensations to the thalamus.
在这项研究中，我们研究了 NF200-、甘丙肽-、神经肽 Y（NPY）-和神经元型一氧化氮合酶（nNOS）-样免疫反应性（LI）背根神经节（DRG）神经元中甘丙肽受体 2（GalR2）表达的时间变化在正中神经慢性缩窄性损伤（CCI）后，以及 GalR2 对楔束核（CN）中 c-Fos 表达的影响。我们使用双重免疫荧光标记方法评估 CCI 后 NF200-LI、甘丙肽-LI、NPY-LI 和 nNOS-LI DRG 神经元中 GalR2 表达的变化。von Frey 测定法用于评估 CCI 大鼠足底注射生理盐水、M871（GalR2 拮抗剂）或 AR-M1896（GalR2 激动剂）对神经病理性体征的疗效。所有治疗均评估了 c-Fos 表达变化的影响。损伤 DRG 中 GalR2-LI 神经元的百分比增加，并在 CCI 后 1 周达到峰值。我们进一步发现，CCI 后 NF200、甘丙肽、NPY 和 nNOS 标记的 GalR2-LI 神经元的百分比明显增加。此外，M871 显著减轻触觉过敏，但 AR-M1896 治疗后感觉略有加重。因此，CCI 治疗的正中神经电刺激后，楔束核（CN）中 c-Fos-LI 神经元的数量在 M871 组中显著减少，而在 AR-M1896 组中增加。这些结果表明，GalR2 的激活可能通过 NPY 或一氧化氮诱导 CN 中的 c-Fos 表达，并将机械性痛觉过敏感觉传递到丘脑。
