Traub R J, Sengupta J N, Gebhart G F
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242, USA.
Neuroscience. 1996 Oct;74(3):873-84. doi: 10.1016/0306-4522(96)00173-x.
c-Fos has been used as a marker for activity in the spinal cord following noxious somatic or visceral stimulation. Although the viscera receive dual afferent innervation, distention of hollow organs (i.e. esophagus, stomach, descending colon and rectum) induces significantly more c-Fos in second order neurons in the nucleus of the solitary tract and lumbosacral spinal cord, which receive parasympathetic afferent input (vagus, pelvic nerves), than the thoracolumbar spinal cord, which receives sympathetic afferent input (splanchnic nerves). The purpose of this study was to determine the contribution of sympathetic and parasympathetic afferent input to c-Fos expression in the nucleus of the solitary tract and spinal cord, and the influence of supraspinal pathways on Fos induction in the thoracolumbar spinal cord. Noxious gastric distention to 80 mmHg (gastric distension/80) was produced by repetitive inflation of a chronically implanted gastric balloon. Gastric distension/80 induced c-Fos throughout the nucleus of the solitary tract, with the densest labeling observed within 300 microns of the rostral pole of the area postrema. This area was analysed quantitatively following several manipulations. Gastric distension/80 induced a mean of 724 c-Fos-immunoreactive nuclei per section. Following subdiaphragmatic vagotomy plus distention (vagotomy/80), the induction of c-Fos-immunoreactive nuclei was reduced to 293 per section, while spinal transection at T2 plus distention (spinal transection/80) induced a mean of 581 nuclei per nucleus of the solitary tract section. Gastric distension/80 and vagotomy/80 induced minimal c-Fos in the T8-T10 spinal cord (50 nuclei/section), but spinal transection/80 induced 200 nuclei per section. Repetitive bolus injections of norepinephrine produced transient pressor responses mimicking the pressor response produced by gastric distension/80. This manipulation induced minimal c-Fos in the nucleus of the solitary tract and none in the spinal cord. It is concluded that noxious visceral input via parasympathetic vagal afferents, and to a lesser extent sympathetic afferents and the spinosolitary tract, contribute to gastric distention-induced c-Fos in the nucleus of the solitary tract. The induction of c-Fos in the nucleus of the solitary tract is significantly greater than in the viscerotopic segments of the spinal cord, which is partially under tonic descending inhibition, but is not subject to modulation by vagal gastric afferents. Distention pressures produced by noxious gastric distention are much greater than those produced during feeding, suggesting that c-Fos induction in the nucleus of the solitary tract to noxious distention is not associated with physiological mechanisms of feeding and satiety. The large vagal nerve-mediated induction of c-Fos in the nucleus of the solitary tract following gastric distension suggests that parasympathetic afferents contribute to the processing of noxious visceral stimuli, perhaps by contributing to the affective-emotional component of visceral pain.
c-Fos已被用作伤害性躯体或内脏刺激后脊髓活动的标志物。虽然内脏接受双重传入神经支配，但中空器官（即食管、胃、降结肠和直肠）扩张在接受副交感传入输入（迷走神经、盆神经）的孤束核和腰骶脊髓的二级神经元中诱导产生的c-Fos，比接受交感传入输入（内脏神经）的胸腰脊髓中诱导产生的c-Fos明显更多。本研究的目的是确定交感和副交感传入输入对孤束核和脊髓中c-Fos表达的贡献，以及脊髓上通路对胸腰脊髓中Fos诱导的影响。通过对慢性植入的胃球囊进行反复充气，产生80 mmHg的伤害性胃扩张（胃扩张/80）。胃扩张/80在整个孤束核诱导产生c-Fos，在最后区嘴侧极300微米范围内观察到最密集的标记。在进行几种操作后对该区域进行了定量分析。胃扩张/80每切片平均诱导产生724个c-Fos免疫反应性细胞核。膈下迷走神经切断术加扩张（迷走神经切断术/80）后，c-Fos免疫反应性细胞核的诱导减少到每切片293个，而在T2水平脊髓横断加扩张（脊髓横断/80）每孤束核切片平均诱导产生581个细胞核。胃扩张/80和迷走神经切断术/80在T8 - T10脊髓中诱导产生的c-Fos极少（50个细胞核/切片），但脊髓横断/80每切片诱导产生20（此处原文可能有误，推测应为200）个细胞核。重复推注注射去甲肾上腺素产生短暂的升压反应，模拟胃扩张/80产生的升压反应。这种操作在孤束核中诱导产生的c-Fos极少，在脊髓中未诱导产生。得出的结论是，通过副交感迷走传入神经的伤害性内脏输入，以及在较小程度上交感传入神经和脊髓-孤束，对胃扩张诱导的孤束核中的c-Fos有贡献。孤束核中c-Fos的诱导明显大于脊髓内脏定位节段中的诱导，脊髓内脏定位节段部分受紧张性下行抑制，但不受迷走胃传入神经的调节。伤害性胃扩张产生的扩张压力远大于进食期间产生的压力，这表明孤束核对伤害性扩张的c-Fos诱导与进食和饱腹感的生理机制无关。胃扩张后迷走神经介导的孤束核中c-Fos的大量诱导表明，副交感传入神经可能通过对内脏痛的情感-情绪成分的贡献，参与伤害性内脏刺激的处理。
