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超微结构证据表明,在脊髓背角存在催产素和催产素受体:疼痛调节的机制。

Ultrastructural Evidence for Oxytocin and Oxytocin Receptor at the Spinal Dorsal Horn: Mechanism of Nociception Modulation.

机构信息

Departamento de Neurobiología del Desarrollo y Neurofisiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, Querétaro, QRO 76230, México.

Unidad de Microscopía, Microscopía Electrónica de Transmisión, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM Juriquilla, Querétaro, QRO 76230, México.

出版信息

Neuroscience. 2021 Nov 1;475:117-126. doi: 10.1016/j.neuroscience.2021.09.004. Epub 2021 Sep 14.

DOI:10.1016/j.neuroscience.2021.09.004
PMID:34530103
Abstract

Oxytocin is a hypothalamic neuropeptide involved in the inhibition of nociception transmission at spinal dorsal horn (SDH) level (the first station where the incoming peripheral signals is modulated). Electrophysiological, behavioral, and pharmacological data strongly support the role of this neuropeptide and its receptor (the oxytocin receptor, OTR) as a key endogenous molecule with analgesic properties. Briefly, current data showed that oxytocin release from the hypothalamus induces OTR activation at the SDH, inducing selective inhibition of the nociceptive Aδ- and C-fibers (probably peptidergic) activity, but not the activity of proprioceptive fibers (i.e. Aβ-fibers). The above inhibition could be a direct presynaptic mechanism, or a mechanism mediated by GABAergic interneurons. However, the exact anatomical localization of oxytocin and OTR remains unclear. In this context, the present study set out to analyze the role of OTRs, GABAergic cells and CGRP fibers in the SDH in rats by using electron microscopy. Ultrastructural analyses of the SDH tissue show that: (i) oxytocin and OTR are found in asymmetrical synapsis; (ii) OTR is found in GABAergic interneurons (near unmyelinated fibers), CGRPergic fibers and glial cells; (iii) whereas oxytocin is present in supraspinal descending projection fibers. These anatomical data strongly support the notion that oxytocin released at the SDH could presynaptically inhibit the nociceptive input from the peripheral primary afferent fibers. This inhibitory action could be direct or use a GABA interneuron. Furthermore, our findings that OTR is exhibited in glial tissue at the SDH requires further exploration in nociception assays.

摘要

催产素是一种下丘脑神经肽,参与抑制脊髓背角(SDH)水平的伤害性感觉传递(传入的外周信号在该处被调节)。电生理学、行为学和药理学数据强烈支持这种神经肽及其受体(催产素受体,OTR)作为具有镇痛特性的内源性关键分子的作用。简而言之,目前的数据表明,来自下丘脑的催产素释放诱导 SDH 中的 OTR 激活,诱导对伤害性 Aδ-和 C-纤维(可能是肽能)活性的选择性抑制,但不影响本体感受纤维(即 Aβ-纤维)的活性。这种抑制可能是一种直接的突触前机制,或者是一种由 GABA 能中间神经元介导的机制。然而,催产素和 OTR 的确切解剖定位尚不清楚。在这种情况下,本研究旨在通过电子显微镜分析大鼠 SDH 中的 OTR、GABA 能细胞和 CGRP 纤维的作用。SDH 组织的超微结构分析表明:(i)催产素和 OTR 存在于不对称突触中;(ii)OTR 存在于 GABA 能中间神经元(靠近无髓纤维)、CGRP 能纤维和神经胶质细胞中;(iii)而催产素存在于脊髓上行投射纤维中。这些解剖学数据强烈支持这样一种观点,即 SDH 释放的催产素可以在突触前抑制来自外周初级传入纤维的伤害性输入。这种抑制作用可以是直接的,也可以使用 GABA 中间神经元。此外,我们在 SDH 处发现 OTR 存在于神经胶质组织中的发现需要在疼痛检测中进一步探索。

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