Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC, Australia; Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, VIC, Australia.
Department of Medical Imaging and Radiation Sciences, Monash University, Clayton, VIC, Australia.
EBioMedicine. 2024 Feb;100:104976. doi: 10.1016/j.ebiom.2024.104976. Epub 2024 Jan 19.
Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory nerve responsivity to tussive stimuli which would be accompanied by alterations in stimulus-induced brainstem activation, measurable with functional magnetic resonance imaging (fMRI).
We investigated brainstem responses during inhalation of capsaicin and adenosine triphosphate (ATP) in 29 participants with chronic cough and 29 age- and sex-matched controls. Psychophysical testing was performed to evaluate individual sensitivities to inhaled stimuli and fMRI was used to compare neural activation in participants with cough and control participants while inhaling stimulus concentrations that evoked equivalent levels of urge-to-cough sensation.
Participants with chronic cough were significantly more sensitive to inhaled capsaicin and ATP and showed a change in relationship between urge-to-cough perception and cough induction. When urge-to-cough levels were matched, participants with chronic cough displayed significantly less neural activation in medullary regions known to integrate airway sensory inputs. By contrast, neural activations did not differ significantly between the two groups in cortical brain regions known to encode cough sensations whereas activation in a midbrain region of participants with chronic cough was significantly increased compared to controls.
Cough hypersensitivity in some patients may occur in brain circuits above the level of the medulla, perhaps involving midbrain regions that amplify ascending sensory signals or change the efficacy of central inhibitory control systems that ordinarily serve to filter sensory inputs.
Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Pty Ltd. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme (Australia) Pty Ltd.
慢性咳嗽是一种普遍且难以治疗的病症，常伴有咳嗽高敏性，其特征是接触低水平感觉刺激即可引发咳嗽。咳嗽高敏性的机制可能涉及气道感觉神经对咳嗽刺激反应性的改变，这将伴随着刺激诱导的脑干激活的改变，可通过功能磁共振成像（fMRI）来测量。
我们研究了 29 名慢性咳嗽患者和 29 名年龄和性别匹配的对照者在吸入辣椒素和三磷酸腺苷（ATP）时的脑干反应。进行了心理物理学测试以评估个体对吸入性刺激的敏感性，并用 fMRI 比较了咳嗽患者和对照者在吸入引起等效咳嗽冲动感觉的刺激浓度时的神经激活。
慢性咳嗽患者对吸入的辣椒素和 ATP 更为敏感，并且咳嗽诱发与咳嗽冲动感知之间的关系发生了变化。当咳嗽冲动水平相匹配时，慢性咳嗽患者在已知整合气道感觉输入的延髓区域的神经激活明显减少。相比之下，两组在已知编码咳嗽感觉的皮质脑区的神经激活没有显著差异，而慢性咳嗽患者的中脑区域的激活明显增加。
一些患者的咳嗽高敏性可能发生在延髓水平以上的脑回路中，可能涉及中脑区域，这些区域可能增强上行感觉信号或改变中枢抑制控制系统的效力，中枢抑制控制系统通常用于过滤感觉输入。
部分由默克 Sharp & Dohme Pty Ltd 发起的研究计划资助。本文表达的观点是作者的观点，不一定代表默克 Sharp & Dohme（澳大利亚）Pty Ltd 的观点。
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