Liu C Y, Mueller M H, Grundy D, Kreis M E
Institute of Physiology, School of Medicine, Shandong University, Shandong, China.
Am J Physiol Gastrointest Liver Physiol. 2007 May;292(5):G1213-20. doi: 10.1152/ajpgi.00267.2006. Epub 2007 Jan 4.
The central nervous system modulates inflammation in the gastrointestinal tract via efferent vagal pathways. We hypothesized that these vagal efferents receive synaptic input from vagal afferents, representing an autonomic feedback mechanism. The consequence of this vagovagal reflex for afferent signal generation in response to LPS was examined in the present study. Different modifications of the vagal innervation or sham procedures were performed in anesthetized rats. Extracellular mesenteric afferent nerve discharge and systemic blood pressure were recorded in vivo before and after systemic administration of LPS (6 mg/kg iv). Mesenteric afferent nerve discharge increased dramatically following LPS, which was unchanged when vagal efferent traffic was eliminated by acute vagotomy. In chronically vagotomized animals, to eliminate both vagal afferent and efferent traffic, the increase in afferent firing 3.5 min after LPS was reduced to 3.2 +/- 2.5 impulses/s above baseline compared with 42.2 +/- 2.0 impulses/s in controls (P < 0.001). A similar effect was observed following perivagal capsaicin, which was used to eliminate vagal afferent traffic only. LPS also caused a transient hypotension (<10 min), a partial recovery, and then persistent hypertension that was exacerbated by all three procedures. Mechanosensitivity was increased 15 min following LPS but had recovered at 30 min in all subgroups except for the chronic vagotomy group. In conclusion, discharge in capsaicin-sensitive mesenteric vagal afferents is augmented following systemic LPS. This activity, through a vagovagal pathway, helps to attenuate the effects of septic shock. The persistent hypersensitivity to mechanical stimulation after chronic vagal denervation suggests that the vagus exerts a regulatory influence on spinal afferent sensitization following LPS.
中枢神经系统通过传出迷走神经通路调节胃肠道炎症。我们推测这些迷走神经传出纤维接受来自迷走神经传入纤维的突触输入，这代表一种自主反馈机制。本研究检测了这种迷走神经反射对脂多糖（LPS）刺激下传入信号产生的影响。在麻醉大鼠中进行了不同的迷走神经支配改变或假手术操作。在静脉注射LPS（6 mg/kg）前后，在体记录细胞外肠系膜传入神经放电和全身血压。LPS注射后肠系膜传入神经放电显著增加，急性迷走神经切断消除迷走神经传出活动时，该放电无变化。在慢性迷走神经切断的动物中，为消除迷走神经传入和传出活动，LPS注射3.5分钟后传入神经放电增加量降至比基线高3.2±2.5次/秒，而对照组为42.2±2.0次/秒（P<0.001）。仅用于消除迷走神经传入活动的迷走神经周围注射辣椒素后也观察到类似效果。LPS还引起短暂低血压（<10分钟）、部分恢复，然后是持续性高血压，这三种操作均使高血压加剧。LPS注射1十五分钟后机械敏感性增加，但除慢性迷走神经切断组外，所有亚组在30分钟时均已恢复。总之，全身注射LPS后，辣椒素敏感的肠系膜迷走神经传入纤维放电增强。这种活动通过迷走神经反射通路有助于减轻脓毒性休克的影响。慢性迷走神经去神经支配后对机械刺激的持续超敏反应表明，迷走神经对LPS刺激后脊髓传入神经致敏具有调节作用。
