Estrogen augmented visceral pain and colonic neuron modulation in a double-hit model of prenatal and adult stress  

作　　者：Jing-Hong Chen Ying Sun Pei-Jun Ju Jin-Bao Wei Qing-Jie Li John H Winston 

机构地区：[1]Shanghai Key Laboratory of Psychotic Disorders,Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China [2]Department of Internal Medicine,University of Texas Medical Branch,Galveston,TX 77555,United States

出　　处：《World Journal of Gastroenterology》2021年第30期5060-5075,共16页世界胃肠病学杂志（英文版）

基　　金：NIDDK,No.5R01DK111819-03 and No.5R01DK032346-28;National Natural Science Foundation of China,No.81571326.

摘　　要：BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent way.Combining adult stress in offspring will increase this sensitivity.Based on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models,we predicted that chronic prenatal stress(CPS)+chronic adult stress(CAS)will maximize visceral hyperalgesia;and that estrogen plays an important role in colonic hyperalgesia.AIM The aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying mechanisms.METHODS We established a CPS plus CAS rodent model in which the balloon was used to distend the colorectum.The single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s activity.The reverse transcription-polymerase chain reaction,western blot,and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent sensitivity.We used ovariectomy and letrozole to reduce estrogen levels of female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent sensitization.RESULTS Spontaneous activity and single fiber activity were significantly greater in females than in males.The enhanced sensitization in female rats mainly came from lowthreshold neurons.CPS significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in response.Activity was further enhanced by CAS.In addition,the excitability of colon-projecting dorsal root ganglion(DRG)neurons increased in CPS+CAS rats and was associated with a decrease in transient Atype K+currents.Compared with ovariectomy,treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats,confirming the gender difference.Moreover,mice treated with letrozole had decreased colonic DRG neuron excitability.The intrathecal infusion of estrogen increased brain-derived neurotrophic factor(BDNF)protein levels and contributed to the response

关 键 词：Chronic prenatal stress ESTROGEN Visceral pain Neuronal sensitization EXCITABILITY LETROZOLE 

分 类 号：R574.4[医药卫生—消化系统]