Martínez Vicente, Wang Lixin, Taché Yvette
CURE: Digestive Diseases Research Center, Division of Digestive Diseases, David Geffen School of Medicine, University of California at Los Angeles, and VA Greater Los Angeles Healthcare System, 90073, USA.
Brain Res. 2006 May 1;1086(1):168-80. doi: 10.1016/j.brainres.2006.02.063. Epub 2006 Apr 13.
We assessed brain nuclei activated during noxious mechanical distension of the proximal colon in conscious rats, using Fos as a marker of neuronal activation, and functional reflex changes in gastric emptying associated to colon distension. The role of capsaicin-sensitive afferents in Fos and gastric responses to distension was also investigated. Compared with sham distension, isovolumetric phasic distension of the proximal colon (10 ml, 30 s on/off for 10 min) increased significantly Fos expression 1 h after distension in selective brain areas, most prominently, the paraventricular and supraoptic nuclei of the hypothalamus (13-fold and 80-fold, respectively), the locus coeruleus-Barrington's nucleus complex (2-fold), area postrema (7-fold) and the nucleus tractus solitarius (4-fold). Increased Fos expression was also observed in the cingulate cortex, posterior paraventricular nucleus of the thalamus, periaqueductal gray and ventrolateral medulla. Distension of the proximal colon significantly inhibited gastric emptying by 82% and 34%, as measured 30 and 60 min after the distension respectively, compared with control. Pretreatment with systemic capsaicin prevented both the brain increase in Fos expression and the inhibition of gastric emptying induced by the colon distension. These results show that visceral pain arising from the proximal colon activates a complex neuronal network that includes specific brain nuclei involved in the integration of autonomic, neuroendocrine and behavioral responses to pain and an inhibitory motor reflex in other gut areas (delayed gastric emptying). Capsaicin-sensitive afferent pathways are involved in mediating brain neuronal activation and functional changes associated with noxious visceral stimulation.
我们使用Fos作为神经元激活的标志物，评估清醒大鼠近端结肠有害机械扩张期间激活的脑核，以及与结肠扩张相关的胃排空功能反射变化。还研究了辣椒素敏感传入神经在Fos和胃对扩张反应中的作用。与假扩张相比，近端结肠等容性相性扩张（10毫升，开/关30秒，共10分钟）在扩张后1小时显著增加了选择性脑区的Fos表达，最显著的是下丘脑室旁核和视上核（分别增加13倍和80倍）、蓝斑-巴林顿核复合体（增加2倍）、最后区（增加7倍）和孤束核（增加4倍）。在扣带回皮质、丘脑后室旁核、导水管周围灰质和延髓腹外侧也观察到Fos表达增加。与对照组相比，近端结肠扩张分别在扩张后30分钟和60分钟测量时显著抑制胃排空82%和34%。全身给予辣椒素预处理可防止结肠扩张引起的脑Fos表达增加和胃排空抑制。这些结果表明，近端结肠产生的内脏痛激活了一个复杂的神经元网络，该网络包括参与对疼痛的自主、神经内分泌和行为反应整合的特定脑核，以及其他肠道区域的抑制性运动反射（胃排空延迟）。辣椒素敏感传入通路参与介导与有害内脏刺激相关的脑神经元激活和功能变化。
