GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain

IF 3.5 3区医学 Q2 NEUROSCIENCES

Frontiers in Molecular Neuroscience Pub Date : 2024-05-09 DOI:10.3389/fnmol.2024.1160435

Haiyan Zheng, Minseok Kim, Chaeun Kim, Yerin Kim, Pyung Sun Cho, Ji Yeon Lim, Hojin Lee, Hye-In Yun, Jungmin Choi, Sun Wook Hwang

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Abstract

The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.

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GnRH 外周调节痛觉感受器功能，加剧机械性疼痛

外周痛觉感受器是向大脑传递疼痛信号的神经元，其功能经常受到局部和全身调节物质的影响。在这种情况下，神经激素效应正在成为一种重要的调节机制，但仍有许多方面有待阐明。在这里，我们报告了促性腺激素释放激素（GnRH），一种大脑特异性神经激素，可以通过作用于小鼠的痛觉感受器而加重疼痛。GnRH 和 GnRHR（GnRH 的受体）在痛觉感受器亚群中表达。给小鼠注射 GnRH 及其类似物可选择性地影响外周神经元，从而减轻机械性疼痛，这种疼痛在神经病理性条件下可重复出现。体外 GnRH 治疗促进了痛觉感受器的功能，这似乎涉及特定的感觉瞬时受体电位离子通道。这些数据表明，外周 GnRH 能以其受体特异性的方式积极调节痛觉感受器的活动，从而导致疼痛加剧。我们的研究表明，GnRH 通过外周机制在神经激素疼痛调节中发挥着重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.