Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Neuroscience. 2019 May 15;406:50-61. doi: 10.1016/j.neuroscience.2019.02.027. Epub 2019 Mar 1.
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.
尽管神经性疼痛的发病率很高，但其发病机制仍不清楚。催产素（OXT）是一种已确定的内源性多肽，在下丘脑的视上核（SON）和室旁核（PVN）中产生。OXT 由 SON 和 PVN 的大细胞部分（mPVN）中的 OXT 神经元合成，被输送到垂体后叶（PP），然后释放到全身血液循环中。同时，PVN 的小细胞部分（pPVN）中的含有 OXT 的神经分泌细胞直接投射到脊髓，并与感觉调制有关。在这项研究中，使用部分坐骨神经结扎（PSL）诱导的大鼠神经性疼痛模型，研究了下丘脑-神经垂体和下丘脑-脊髓通路上的 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，观察到机械性痛觉过敏，并通过免疫组织化学证实了神经胶质细胞的激活。在这个神经性疼痛模型中，在 PP、SON、mPVN 和 pPVN 中观察到 OXT-mRFP1 表达的显著增加。此外，在同侧背角的 I 和 II 层中，具有阳性荧光反应的 OXT-mRFP1 颗粒明显增加。尽管 OXT 的血浆浓度没有显著变化，但在 SON、mPVN 和 pPVN 中观察到 OXT 和 mRFP1 的 mRNA 水平显著增加。这些结果表明，PSL 诱导的神经性疼痛上调了下丘脑 OXT 的合成和运输，使其到达 PP 和脊髓的 OXT 能轴突末端。
