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在伴有抑郁样行为的神经病理性疼痛的临床前模型中缰核的激活模式。

Habenula activation patterns in a preclinical model of neuropathic pain accompanied by depressive-like behaviour.

机构信息

Division of Neuroscience, Hospital Sírio-Libanês, São Paulo, Brazil.

Neuroscience and Mental Health, Hospital for Sick Children Research Institute, Toronto, Canada.

出版信息

PLoS One. 2022 Jul 12;17(7):e0271295. doi: 10.1371/journal.pone.0271295. eCollection 2022.

Abstract

Pain and depression are complex disorders that frequently co-occur, resulting in diminished quality of life. The habenula is an epithalamic structure considered to play a pivotal role in the neurocircuitry of both pain and depression. The habenula can be divided into two major areas, the lateral and medial habenula, that can be further subdivided, resulting in 6 main subregions. Here, we investigated habenula activation patterns in a rat model of neuropathic pain with accompanying depressive-like behaviour. Wistar rats received active surgery for the development of neuropathic pain (chronic constriction injury of the sciatic nerve; CCI), sham surgery (surgical control), or no surgery (behavioural control). All animals were evaluated for mechanical nociceptive threshold using the paw pressure test and depressive-like behaviour using the forced swimming test, followed by evaluation of the immunoreactivity to cFos-a marker of neuronal activity-in the habenula and subregions. The Open Field Test was used to evaluate locomotor activity. Animals with peripheral neuropathy (CCI) showed decreased mechanical nociceptive threshold and increased depressive-like behaviour compared to control groups. The CCI group presented decreased cFos immunoreactivity in the total habenula, total lateral habenula and lateral habenula subregions, compared to controls. No difference was found in cFos immunoreactivity in the total medial habenula, however when evaluating the subregions of the medial habenula, we observed distinct activation patterns, with increase cFos immunoreactivity in the superior subregion and decrease in the central subregion. Taken together, our data suggest an involvement of the habenula in neuropathic pain and accompanying depressive-like behaviour.

摘要

疼痛和抑郁是两种复杂的疾病,它们经常同时发生,导致生活质量下降。缰核是一个位于间脑的结构,被认为在疼痛和抑郁的神经回路中起着关键作用。缰核可以分为两个主要区域,外侧缰核和内侧缰核,它们可以进一步细分,形成 6 个主要的亚区。在这里,我们研究了伴有抑郁样行为的神经病理性疼痛大鼠模型中缰核的激活模式。Wistar 大鼠接受了主动手术以建立神经病理性疼痛模型(坐骨神经慢性缩窄性损伤;CCI)、假手术(手术对照)或不手术(行为对照)。所有动物均通过足底压力测试评估机械性痛觉阈值,通过强迫游泳测试评估抑郁样行为,然后评估缰核和亚区中 cFos 的免疫反应——神经元活动的标志物。旷场测试用于评估运动活动。与对照组相比,患有周围神经病变(CCI)的动物表现出机械性痛觉阈值降低和抑郁样行为增加。CCI 组的缰核总核、外侧缰核总核和外侧缰核亚区的 cFos 免疫反应性降低。总内侧缰核的 cFos 免疫反应性没有差异,但是当评估内侧缰核的亚区时,我们观察到不同的激活模式,上亚区的 cFos 免疫反应性增加,中亚区的 cFos 免疫反应性降低。综上所述,我们的数据表明缰核参与了神经病理性疼痛和伴随的抑郁样行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05e6/9275703/76a5f63e953a/pone.0271295.g001.jpg

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