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

World Journal of Gastroenterology 2021年第30期27卷 5060-5075页

作者： Jing-Hong Chen Ying Sun Pei-Jun Ju Jin-Bao Wei Qing-Jie Li John H Winston Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Internal Medicine University of Texas Medical BranchGalvestonTX 77555United States

BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent *** adult stress in offspring will increase this *** 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 *** The aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying *** We established a CPS plus CAS rodent model in which the balloon was used to distend the *** single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s *** reverse transcription-polymerase chain reaction,western blot,and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent *** 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 *** Spontaneous activity and single fiber activity were significantly greater in females than in *** enhanced sensitization in female rats mainly came from lowthreshold *** significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in *** was further enhanced by *** 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+*** with ovariectomy,treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats,confirming the gender ***,mice treated with letrozole had decreased colonic DRG neuron *** intrathecal infusion of estrogen increased brain-derived neurotrophic factor(BDNF)p

关键词： Chronic prenatal stress Estrogen Visceral pain neuronal sensitization Excitability Letrozole

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