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Evidence for engagement of the nucleus of the solitary tract in processing intestinal chemonociceptive input irrespective of conscious pain response in healthy humans
Pain ( IF 7.4 ) Pub Date : 2022-08-01 , DOI: 10.1097/j.pain.0000000000002538
Abraham B Beckers 1 , Lukas van Oudenhove 2, 3 , Zsa Zsa R M Weerts 1 , Heidi I L Jacobs 4, 5 , Nikos Priovoulos 6 , Benedikt A Poser 7 , Dimo Ivanov 7 , Ali Gholamrezaei 8 , Qasim Aziz 9 , Sigrid Elsenbruch 10, 11 , Ad A M Masclee 1 , Daniel Keszthelyi 1
Affiliation  

Neuroimaging studies have revealed important pathomechanisms related to disorders of brain–gut interactions, such as irritable bowel syndrome and functional dyspepsia. More detailed investigations aimed at neural processing in the brainstem, including the key relay station of the nucleus of the solitary tract (NTS), have hitherto been hampered by technical shortcomings. To ascertain these processes in more detail, we used multiecho multiband 7T functional magnetic resonance imaging and a novel translational experimental model based on a nutrient-derived intestinal chemonociceptive stimulus. In a randomized cross-over fashion, subjects received duodenal infusion of capsaicin (the pungent principle in red peppers) and placebo (saline). During infusion, functional magnetic resonance imaging data and concomitant symptom ratings were acquired. Of 26 healthy female volunteers included, 18 were included in the final analysis. Significantly increased brain activation over time during capsaicin infusion, as compared with placebo, was observed in brain regions implicated in pain processing, in particular the NTS. Brain activation in the thalamus, cingulate cortex, and insula was more pronounced in subjects who reported abdominal pain (visual analogue scale > 10 mm), as compared with subjects who experienced no pain. On the contrary, activations at the level of the NTS were independent of subjective pain ratings. The current experimental paradigm therefore allowed us to demonstrate activation of the principal relay station for visceral afferents in the brainstem, the NTS, which was engaged irrespective of the conscious pain response. These findings contribute to understanding the fundamental mechanism necessary for developing novel therapies aimed at correcting disturbances in visceral afferent pain processing.



中文翻译:

无论健康人有意识的疼痛反应如何,孤束核参与处理肠道化学伤害输入的证据

神经影像学研究揭示了与脑肠相互作用紊乱相关的重要病理机制,例如肠易激综合征和功能性消化不良。迄今为止,针对脑干神经处理(包括孤束核(NTS)的关键中继站)的更详细的研究一直受到技术缺陷的阻碍。为了更详细地确定这些过程,我们使用了多回波多频带 7T 功能磁共振成像和基于营养源性肠道化学伤害刺激的新型转化实验模型。以随机交叉方式,受试者接受十二指肠输注辣椒素(红辣椒中的辛辣成分)和安慰剂(盐水)。在输注过程中,获取功能性磁共振成像数据和伴随症状评级。在纳入的 26 名健康女性志愿者中,18 名进入最终分析。与安慰剂相比,随着时间的推移,在辣椒素输注过程中,与疼痛处理有关的大脑区域(特别是 NTS)观察到大脑激活显着增加。与没有经历疼痛的受试者相比,报告腹痛(视觉模拟量表> 10毫米)的受试者的丘脑、扣带皮层和岛叶的大脑激活更为明显。相反,NTS 水平的激活与主观疼痛评级无关。因此,当前的实验范式使我们能够证明脑干内脏传入的主要中继站 NTS 的激活,无论有意识的疼痛反应如何,该中继站都会被激活。这些发现有助于理解开发旨在纠正内脏传入疼痛处理紊乱的新疗法所需的基本机制。

更新日期:2022-07-18
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