Eijkelkamp Niels, Kavelaars Annemieke, Elsenbruch Sigrid, Schedlowski Manfred, Holtmann Gerald, Heijnen Cobi J
Laboratory for Psychoneuroimmunology, Univ. Medical Center Utrecht, Rm. KC 03.063.0, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G749-57. doi: 10.1152/ajpgi.00114.2007. Epub 2007 Jul 26.
During acute and chronic inflammation visceral pain perception is altered. Conflicting data exist, however, on visceral pain perception in the postinflammatory phase. The aim of the present study was to investigate whether visceral pain perception is altered after resolution of dextran sodium sulfate (DSS)-induced inflammation of the colon. Visceral sensory function in mice was assessed by monitoring behavioral responses to intracolonic capsaicin instillation. Two hours later the number of c-Fos-positive neurons in lamina I/II and X of spinal cord segments T(12/13)-S1 was determined as a measure of neuronal activation. DSS colitis was induced by adding 1% of DSS to the drinking water. The course of DSS-induced colitis was assessed by determining the disease activity index score. Animals developed a transient colitis and had recovered at day 49. At this time point, cytokine levels and colon length were similar to control animals. Importantly, after resolution of DSS-induced colitis the behavioral response to intracolonic capsaicin was increased compared with control mice. Moreover, capsaicin-induced spinal cord neuronal c-Fos expression was significantly increased. Interestingly, after colitis animals also exhibited referred somatic hyperalgesia as measured with von Frey hairs on the abdominal wall. We conclude that postinflammatory visceral hyperalgesia occurs after resolution of DSS-induced colitis and that capsaicin-induced behavioral responses and spinal cord neuronal c-Fos activation are effective readouts for determination of visceral pain perception.
在急性和慢性炎症过程中,内脏痛觉会发生改变。然而,关于炎症后阶段的内脏痛觉,存在相互矛盾的数据。本研究的目的是调查葡聚糖硫酸钠(DSS)诱导的结肠炎症消退后,内脏痛觉是否发生改变。通过监测小鼠对结肠内注入辣椒素的行为反应来评估其内脏感觉功能。两小时后,测定脊髓T(12/13)-S1节段I/II层和X层中c-Fos阳性神经元的数量,作为神经元激活的指标。通过向饮用水中添加1%的DSS来诱导DSS结肠炎。通过确定疾病活动指数评分来评估DSS诱导的结肠炎病程。动物出现短暂性结肠炎,并在第49天恢复。此时,细胞因子水平和结肠长度与对照动物相似。重要的是,DSS诱导的结肠炎消退后,与对照小鼠相比,对结肠内辣椒素的行为反应增强。此外,辣椒素诱导的脊髓神经元c-Fos表达显著增加。有趣的是,结肠炎后动物在腹壁上用von Frey毛发测量时也表现出牵涉性躯体痛觉过敏。我们得出结论,DSS诱导的结肠炎消退后会发生炎症后内脏痛觉过敏,并且辣椒素诱导的行为反应和脊髓神经元c-Fos激活是确定内脏痛觉的有效指标。