Gut Enterochromaffin Cells are Critical Drivers of Visceral Pain and Anxiety

嗜铬细胞 肠易激综合征 内脏痛 医学 人口 痛觉过敏 5-羟色胺能 血清素 内科学 受体 伤害 环境卫生
作者
James R. Bayrer,Joel Castro,Archana Venkataramen,Kouki K Touhara,Nathan D. Rossen,Ryan D. Morrie,Aenea Hendry,Jessica Madden,Kristina Braverman,Gudrun Schober,Mariana Brizuela,Carla Bueno Silva,Holly A. Ingraham,Stuart M. Brierley,David Julius
标识
DOI:10.1101/2022.04.04.486775
摘要

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents a significant component of chronic visceral pain 1 . For the growing population afflicted by irritable bowel syndrome (IBS), GI hypersensitivity and pain persist long after signs of tissue injury have resolved 2 . IBS also exhibits a strong sex bias afflicting women three-fold more than men 1 . Identifying the molecules, cells, and circuits that mediate both the acute and persistent phases of visceral pain is a critical first step in understanding how environmental and endogenous factors produce long-term changes in the nervous system or associated tissues to engender chronic pain syndromes 3,4 . Enterochromaffin (EC) cells within the gut epithelium are exceedingly rare sensory neuroendocrine cells that detect and transduce noxious stimuli to nearby nerve endings via serotonin. Here, we manipulate murine EC cell activity using genetic strategies to ascertain their contributions to visceral pain. We show that acute EC cell activation is sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterially derived short-chain fatty acid irritant associated with inflammatory GI disorders. Remarkably, prolonged EC cell activation by itself is sufficient to produce persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Perturbing the activity of these rare EC cells led to a marked increase in anxiety-like behaviors that normalized after blocking serotonergic signaling. Sex differences were also noted across a range of assays, indicating that females have a higher baseline visceral sensitivity. Our findings validate a critical role for EC cell-mucosal afferent signaling in acute and persistent GI pain while highlighting mechanistically defined genetic models for studying visceral hypersensitivity, sex differences, and associated behaviors.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
蝉鸣完成签到,获得积分10
2秒前
3秒前
David完成签到 ,获得积分10
4秒前
姽婳wy发布了新的文献求助10
7秒前
WHY发布了新的文献求助10
8秒前
MissXia完成签到,获得积分10
9秒前
JIANYOUFU发布了新的文献求助10
9秒前
12秒前
风趣的凌丝完成签到,获得积分10
13秒前
GravityStarings完成签到,获得积分10
13秒前
liekkas完成签到,获得积分10
13秒前
wanci应助nano采纳,获得10
14秒前
淡淡从阳发布了新的文献求助10
17秒前
琼琼完成签到 ,获得积分10
19秒前
23秒前
WHY完成签到,获得积分10
23秒前
25秒前
25秒前
25秒前
打打应助哭泣的雪糕采纳,获得10
25秒前
28秒前
WW发布了新的文献求助10
29秒前
29秒前
橙橙妈妈发布了新的文献求助10
30秒前
30秒前
裴子骞发布了新的文献求助10
31秒前
铂铑钯钌完成签到,获得积分10
31秒前
31秒前
Xerxez发布了新的文献求助10
32秒前
月月鸟发布了新的文献求助10
33秒前
35秒前
何觅夏发布了新的文献求助10
38秒前
赘婿应助一只菜鸡采纳,获得10
40秒前
NexusExplorer应助Xianer采纳,获得30
40秒前
gaoyang123完成签到 ,获得积分10
40秒前
不会看文献完成签到,获得积分10
41秒前
43秒前
Akim应助熠熠采纳,获得10
44秒前
hedianmoony发布了新的文献求助10
47秒前
48秒前
高分求助中
LNG地下式貯槽指針(JGA指-107) 1000
LNG地上式貯槽指針 (JGA指 ; 108) 1000
Impact of Mitophagy-Related Genes on the Diagnosis and Development of Esophageal Squamous Cell Carcinoma via Single-Cell RNA-seq Analysis and Machine Learning Algorithms 900
QMS18Ed2 | process management. 2nd ed 600
LNG as a marine fuel—Safety and Operational Guidelines - Bunkering 560
Exploring Mitochondrial Autophagy Dysregulation in Osteosarcoma: Its Implications for Prognosis and Targeted Therapy 500
九经直音韵母研究 500
热门求助领域 (近24小时)
化学 医学 材料科学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 免疫学 细胞生物学 电极
热门帖子
关注 科研通微信公众号,转发送积分 2936433
求助须知:如何正确求助?哪些是违规求助? 2592152
关于积分的说明 6983637
捐赠科研通 2236655
什么是DOI,文献DOI怎么找? 1187910
版权声明 589899
科研通“疑难数据库(出版商)”最低求助积分说明 581484