美国加州大学旧金山分校David Julius等研究人员合作发现，肠道肠嗜铬细胞驱动内脏疼痛和焦虑。这一研究成果于2023年3月22日在线发表在国际学术期刊《自然》上。

研究人员重点关注了肠嗜铬（EC）细胞，它是肠道上皮细胞中罕见的兴奋性、血清素能神经内分泌细胞。EC细胞检测并将有毒刺激转达给附近的粘膜神经末梢，但这一信号通路在内脏疼痛中的参与以及随之而来的性别差异还没有被评估。通过在体内增强或抑制EC细胞的功能，研究人员表明这些细胞足以引起对肠道膨胀的超敏反应，并且是异戊酸酯（一种与消化道炎症有关的细菌性短链脂肪酸）致敏作用的必要条件。

值得注意的是，长时间的EC细胞激活会产生持续的内脏超敏反应，即使没有煽动性的炎症发作。此外，扰乱EC细胞的活动促进了类似焦虑的行为，在阻断了血清素信号后，这些行为又恢复了正常。在一系列范式中注意到性别差异，表明EC细胞-粘膜传入回路在女性中是有影响的。这些研究结果验证了EC细胞-粘膜传入信号在急性和持续性消化道疼痛中的关键作用，此外还强调了研究内脏超敏性和肠道疼痛性别偏差的遗传模型。

据悉，胃肠道（GI）不适是大多数肠道疾病的标志，也是慢性内脏疼痛的一个重要组成部分。对于越来越多的受肠易激综合征困扰的人群来说，消化道的超敏反应和疼痛在组织损伤解决后仍持续存在。肠易激综合征还表现出强烈的性别偏差，女性患者比男性患者多三倍。

附：英文原文

Title: Gut enterochromaffin cells drive visceral pain and anxiety

Author: Bayrer, James R., Castro, Joel, Venkataraman, Archana, Touhara, Kouki K., Rossen, Nathan D., Morrie, Ryan D., Maddern, Jessica, Hendry, Aenea, Braverman, Kristina N., Garcia-Caraballo, Sonia, Schober, Gudrun, Brizuela, Mariana, Castro Navarro, Fernanda M., Bueno-Silva, Carla, Ingraham, Holly A., Brierley, Stuart M., Julius, David

Issue&Volume: 2023-03-22

Abstract: Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain1. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved2. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men1. Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium3,4,5. EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings3,6 but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation7,8. Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell–mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell–mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain.

DOI: 10.1038/s41586-023-05829-8

Source: https://www.nature.com/articles/s41586-023-05829-8