Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin.
Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin.
复制标题
DOI：
10.3389/fnsys.2017.00086
复制
发表时间：
2017
影响因子：
3
通讯作者：
Johnson AC
中科院分区：
文献类型：
--
作者：
Greenwood-Van Meerveld B;Johnson AC
内脏疼痛通常定位不良，其特征在于对刺激（如器官扩张）的超敏反应。与慢性内脏痛相一致，与压力相关的精神障碍包括焦虑和抑郁有很高的共病率。内脏疼痛与这些重叠合并症的机制仍有待阐明。有证据表明，长期的压力促进疼痛感知和敏感的疼痛途径，导致前馈循环促进慢性内脏疼痛疾病，如肠易激综合征（IBS）。早期生活压力（ELS）是IBS发展的一个危险因素，然而ELS对成年期内脏感知的持续影响的机制仍不完全清楚。在啮齿动物模型中，通过束缚和避水诱导的成年动物应激已被用于研究应激诱发疼痛的机制。ELS模型，如母亲分离，有限的嵌套，或气味休克条件反射，试图模拟幼儿期的经验，如忽视，贫困，或虐待照顾者，可以产生慢性的，在成年期的内脏敏感性的性二态性增加。慢性内脏痛是基因×环境相互作用的典型例子，其起因于神经元回路的适应不良变化，导致神经可塑性和异常神经元活动诱导的信号传导。应激对内脏敏感性的持续影响的一个潜在机制可能是基因表达的表观遗传调节。虽然有相对较少的研究检查涉及内脏伤害感受的表观遗传介导的机制，但应激诱导的内脏疼痛与脑内DNA甲基化和组蛋白乙酰化模式的改变有关，导致促伤害性神经递质的表达增加。本文就应激诱发慢性内脏痛加重的神经通路和机制进行综述。此外，我们将审查的重要性，具体的实验模型的成人压力和ELS在提高我们的理解疼痛处理的基本分子机制。
Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress-induced exacerbation of chronic visceral pain. Additionally, we will review the importance of specific experimental models of adult stress and ELS in enhancing our understanding of the basic molecular mechanisms of pain processing.
登录
查看更多内容
DOI：
10.1152/ajpgi.90557.2008
发表时间：
2009-02-01
影响因子：
4.5
作者：
Bradesi, Sylvie;Martinez, Vicente;Mayer, Emeran A.
通讯作者：
Mayer, Emeran A.
影响因子：
7.3
作者：
Alexander SP;Kelly E;Marrion N;Peters JA;Benson HE;Faccenda E;Pawson AJ;Sharman JL;Southan C;Davies JA;CGTP Collaborators
通讯作者：
CGTP Collaborators
影响因子：
3.5
作者：
Bradesi, S;Eutamene, H;Bueno, L
通讯作者：
Bueno, L
影响因子：
7.4
作者：
Agostini, Simona;Eutamene, Helene;Bueno, Lionel
通讯作者：
Bueno, Lionel
影响因子：
3.5
作者：
Aguirre, J. E.;Winston, J. H.;Sarna, S. K.
通讯作者：
Sarna, S. K.