Neuropathic Pain Up-Regulates Hypothalamo-Neurohypophysial and Hypothalamo-Spinal Oxytocinergic Pathways in Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rat
Neuropathic Pain Up-Regulates Hypothalamo-Neurohypophysial and Hypothalamo-Spinal Oxytocinergic Pathways in Oxytocin-Monomeric Red Fluorescent Protein 1 Transgenic Rat
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DOI：
10.1016/j.neuroscience.2019.02.027
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发表时间：
2019-05-15
期刊：
影响因子：
3.3
通讯作者：
Sakai, Akinori
中科院分区：
文献类型：
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作者：
Nishimura, Haruki;Kawasaki, Makoto;Sakai, Akinori
尽管神经性疼痛的发生率很高，但其机制尚不清楚。催产素（OXT）是一种内源性多肽，产生于下丘脑的视上核（SON）和室旁核（PVN）。OXT由SON中的OXT神经元和PVN的大细胞部分（mPVN）合成，被输送到垂体后叶（PP），然后释放到全身血液循环中。同时，PVN （pPVN）旁细胞部分含有oxt的神经分泌细胞直接投射到脊髓并与感觉调节有关。本研究采用部分坐骨神经结扎（PSL）诱导的大鼠神经性疼痛模型，研究下丘脑-神经垂体通路和下丘脑-脊髓通路中的OXT系统。在本研究中，我们使用了表达oxt -单体红色荧光蛋白1 （mRFP1）融合基因的转基因大鼠。在神经性疼痛模型中，观察到机械异常性疼痛，并通过免疫组织化学证实神经胶质细胞活化。在这种神经性疼痛模型中，在PP、SON、mPVN和pPVN中观察到OXT-mRFP1的表达显著增加。与此同时，同侧背角I、II层中荧光反应阳性的OXT-mRFP1颗粒明显增多。虽然血浆中OXT的浓度没有明显变化，但我们观察到SON、mPVN和pPVN中OXT和mRFP1的mRNA水平显著升高。这些结果表明，PSL引起的神经性疼痛上调下丘脑的OXT合成和转运到PP和脊髓的OXT轴突末端。(c) 2019 ibroElsevier Ltd.出版。版权所有。
Despite the high incidence of neuropathic pain, its mechanism remains unclear. Oxytocin (OXT) is an established endogenous polypeptide produced in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus. OXT, which is synthesized by OXT neurons in the SON and the magnocellular part of the PVN (mPVN), is delivered into the posterior pituitary (PP), then released into the systemic blood circulation. Meanwhile, OXT-containing neurosecretory cells in the parvocellular part of the PVN (pPVN) are directly projected to the spinal cord and are associated with sensory modulation. In this study, the OXT system in the hypothalamo-neurohypophysial and hypothalamo-spinal pathway was surveyed using a rat neuropathic pain model induced by partial sciatic nerve ligation (PSL). In the present study, we used transgenic rats expressing an OXT-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In a neuropathic pain model, mechanical allodynia was observed, and glial cell activation was also confirmed via immunohistochemistry. In this neuropathic pain model, a significant increase in the OXT-mRFP1 expression was observed in the PP, the SON, mPVN, and pPVN. Furthermore, OXT-mRFP1 granules with positive fluorescent reaction were remarkably increased in laminae I and II of the ipsilateral dorsal horn. Although the plasma concentrations of OXT did not significantly change, a significant increase of the mRNA levels of OXT and mRFP1 in the SON, mPVN, and pPVN were observed. These results suggest that neuropathic pain induced by PSL upregulates hypothalamic OXT synthesis and transportation to the OXTergic axon terminals in the PP and spinal cord. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.