Schuligoi R, Herzeg G, Wachter C, Jocic M, Holzer P
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Neuroscience. 1996 May;72(2):535-44. doi: 10.1016/0306-4522(95)00552-8.
Expression of the immediate early gene c-fos is considered to be a marker for neuronal activation in the spinal cord in response to afferent input. Since the stomach is continually exposed to injurious chemicals, the present study examined whether application of acid (0.15 M HCl) and formalin (5%) to the gastric mucosa or serosal surface of the stomach stimulates c-fos transcription in the caudal thoracic spinal cord of anaesthetized rats. The spinal cord was removed 15, 45 or 120 min after exposure of the stomach to the noxious chemicals and processed for quantitative in situ hybridization autoradiography of c-fos messenger RNA. Exposure of the gastric mucosa to acid or formalin failed to increase the expression of c-fos messenger RNA in the thoracic spinal cord. Application of acid to the serosal surface of the stomach was also unable to stimulate c-fos transcription, whereas serosal application of formalin led to substantial expression of c-fos messenger RNA in the superficial but also deeper laminae of the spinal dorsal horn when examined 45 min, but not 15 or 120 min, post-stimulation. The highest expression of c-fos messenger RNA was seen when formalin was injected subcutaneously into one hindpaw and c-fos transcription was examined in the lumbar spinal cord. These data indicate that acute exposure of the gastric mucosa to chemical injury does not provide the afferent input which is necessary to cause appreciable c-fos transcription in second order neurons within the spinal cord. Stimulation of the gastric mucosa by acid and formalin was followed, however, by gastric hyperaemia in which spinal afferents releasing vasodilator peptides have been implicated. It is concluded, therefore, that acute stimulation of nociceptive afferents in the stomach causes local homoeostatic reactions but does not necessarily provide afferent input sufficient to recruit spinal nociceptive circuits.
即刻早期基因c-fos的表达被认为是脊髓中神经元对传入输入做出反应而激活的一个标志物。由于胃持续暴露于有害化学物质中，本研究检测了向麻醉大鼠的胃黏膜或浆膜表面施加酸（0.15 M HCl）和福尔马林（5%）是否会刺激胸段尾侧脊髓中的c-fos转录。在胃暴露于有害化学物质15、45或120分钟后取出脊髓，并对c-fos信使核糖核酸进行定量原位杂交放射自显影处理。胃黏膜暴露于酸或福尔马林中未能增加胸段脊髓中c-fos信使核糖核酸的表达。向胃浆膜表面施加酸也无法刺激c-fos转录，而浆膜表面施加福尔马林在刺激后45分钟（而非15或120分钟）检测时，会导致脊髓背角浅层和深层中c-fos信使核糖核酸大量表达。当将福尔马林皮下注射到一只后爪并检测腰段脊髓中的c-fos转录时，观察到c-fos信使核糖核酸的表达最高。这些数据表明，胃黏膜急性暴露于化学损伤不会提供在脊髓内二级神经元中引起明显c-fos转录所需的传入输入。然而，酸和福尔马林刺激胃黏膜后会出现胃充血，其中涉及释放血管舒张肽的脊髓传入神经。因此得出结论，胃中伤害性传入神经的急性刺激会引起局部稳态反应，但不一定提供足以激活脊髓伤害性回路的传入输入。
