Holzer P, Danzer M, Schicho R, Samberger C, Painsipp E, Lippe I T
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, A-8010 Graz, Austria.
Neuroscience. 2004;129(2):439-45. doi: 10.1016/j.neuroscience.2004.07.040.
Exposure of the gastric mucosa to back-diffusing concentrations of HCl (0.25 M, pH 0.51) stimulates vagal afferent input to the brainstem. Here we have examined whether pretreatment of rats with the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha causes sensitization of vagal afferent pathways to HCl. Rats were pretreated i.p. with interleukin-1beta, tumor necrosis factor-alpha (10 microg/kg) or their vehicle (sterile saline) 24, 48 and 96 h before intragastric administration of HCl (0.25 M, 1 ml/100 g). Activation of neurons in the nucleus tractus solitarii was visualized by c-Fos immunohistochemistry 2 h after the HCl challenge. I.p. administration of interleukin-1beta and tumor necrosis factor-alpha alone induced c-Fos in the brainstem, an effect that was gone after 24 h. At this time, however, the effect of HCl to cause expression of c-Fos in the nucleus tractus solitarii was significantly enhanced by pretreatment with interleukin-1beta and tumor necrosis factor-alpha. The sensitizing effect of i.p.-administered interleukin-1beta was sustained for more than 48 h and prevented by the interleukin-1 receptor antagonist anakinra. Intracisternal administration of interleukin-1beta and tumor necrosis factor-alpha (100 ng) failed to amplify the HCl-evoked expression of c-Fos in the brainstem. These results show that peripheral administration of the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha induces prolonged sensitization of vagal afferent pathways to gastric HCl challenge. This effect seems to arise from a peripheral action on vagal afferents and may be of relevance to gastric chemonociception.
胃黏膜暴露于反向扩散的盐酸浓度（0.25 M，pH 0.51）会刺激迷走神经传入脑干。在此，我们研究了用促炎细胞因子白细胞介素-1β和肿瘤坏死因子-α预处理大鼠是否会导致迷走神经传入通路对盐酸敏感。在胃内给予盐酸（0.25 M，1 ml/100 g）前24、48和96小时，给大鼠腹腔注射白细胞介素-1β、肿瘤坏死因子-α（10微克/千克）或其溶剂（无菌生理盐水）。在盐酸刺激后2小时，通过c-Fos免疫组织化学观察孤束核中神经元的激活情况。单独腹腔注射白细胞介素-1β和肿瘤坏死因子-α可诱导脑干中c-Fos表达，这种效应在24小时后消失。然而，此时用白细胞介素-1β和肿瘤坏死因子-α预处理可显著增强盐酸引起孤束核中c-Fos表达的效应。腹腔注射白细胞介素-1β的致敏作用持续超过48小时，并可被白细胞介素-1受体拮抗剂阿那白滞素阻断。脑池内注射白细胞介素-1β和肿瘤坏死因子-α（100纳克）未能增强盐酸诱发的脑干中c-Fos表达。这些结果表明，外周给予促炎细胞因子白细胞介素-1β和肿瘤坏死因子-α可诱导迷走神经传入通路对胃盐酸刺激产生长时间的致敏作用。这种效应似乎源于对迷走神经传入纤维的外周作用，可能与胃化学伤害感受有关。
