Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia
Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia
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DOI：
10.1152/ajpgi.00500.2004
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发表时间：
2005-07-01
影响因子：
4.5
通讯作者：
Mayer, EA
中科院分区：
文献类型：
--
作者：
Bradesi, S;Schwetz, I;Mayer, EA
慢性应激在功能性胃肠道疾病的发生和加重中起重要作用。为了更好地理解这种关系的机制，我们的目的是表征内脏和躯体伤害感受，结肠运动，焦虑相关的行为，和粘膜免疫激活大鼠暴露于10天的慢性心理应激的变化。雄性Wistar大鼠每天提交1小时避水（WA）的压力或假WA连续10天。在基线和慢性WA后测量内脏对结直肠扩张的反应、热躯体伤害感受和对旷场试验的行为反应。在每次WA应激或假WA会话后对粪便颗粒进行计数，作为应激诱导的结肠运动的量度。从两组中收集结肠样本，并通过免疫组化评价结构变化和中性粒细胞浸润、肥大细胞数量，并通过定量RT-PCR评价细胞因子表达。大鼠暴露于慢性WA（但不是假的压力）开发持续内脏痛觉过敏，而只有短暂的变化，在躯体伤害性感受观察。慢性应激大鼠也表现出焦虑样行为，粪便颗粒排泄增加，肥大细胞数量和IL-1 β和IFN-γ表达少量但显著增加。慢性应激后内脏痛觉过敏持续至少一个月。大鼠慢性心理应激导致内脏伤害性感受发生强而持久的改变，但不影响躯体伤害性感受。内脏痛觉过敏与应激致敏的其他行为表现有关，但仅与轻微的结肠免疫激活有关，这与粘膜免疫激活在维持这种现象中的主要作用有关。
Chronic stress plays an important role in the development and exacerbation of symptoms in functional gastrointestinal disorders. To better understand the mechanisms underlying this relationship, we aimed to characterize changes in visceral and somatic nociception, colonic motility, anxiety-related behavior, and mucosal immune activation in rats exposed to 10 days of chronic psychological stress. Male Wistar rats were submitted daily to either 1-h water avoidance (WA) stress or sham WA for 10 consecutive days. The visceromotor response to colorectal distension, thermal somatic nociception, and behavioral responses to an open field test were measured at baseline and after chronic WA. Fecal pellets were counted after each WA stress or sham WA session as a measure of stress-induced colonic motility. Colonic samples were collected from both groups and evaluated for structural changes and neutrophil infiltration, mast cell number by immunohistochemistry, and cytokine expression by quantitative RT-PCR. Rats exposed to chronic WA ( but not sham stress) developed persistent visceral hyperalgesia, whereas only transient changes in somatic nociception were observed. Chronically stressed rats also exhibited anxiety-like behaviors, enhanced fecal pellet excretion, and small but significant increases in the mast cell numbers and the expression of IL-1 beta and IFN-gamma. Visceral hyperalgesia following chronic stress persisted for at least a month. Chronic psychological stress in rats results in a robust and long-lasting alteration of visceral, but not somatic nociception. Visceral hyperalgesia is associated with other behavioral manifestations of stress sensitization but was only associated with minor colonic immune activation arguing against a primary role of mucosal immune activation in the maintenance of this phenomenon.