Holzer P
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria.
J Physiol Pharmacol. 2003 Dec;54 Suppl 4:43-53.
Gastric acid is a factor in the pain associated with peptic ulcer and other acid-related disorders including functional dyspepsia, given that antisecretory treatment is a mainstay in the treatment of upper abdominal pain. However, the molecular sensors, afferent pathways and central processing systems of gastric chemonociception are little known. This article reviews emerging evidence that vagal afferent pathways play a pivotal role in gastric chemonociception. Exposure of the rat gastric mucosa to backdiffusing concentrations of luminal acid is signalled to the brainstem, but not spinal cord, as visualized by functional neuroanatomy based on the rapid expression of c-fos. This observation is complemented by the finding that the visceromotor response to gastric acid challenge is suppressed by vagotomy, but not splanchnectomy. The gastric acid-induced expression of c-fos in the brainstem is reduced by inhibition of gastric acid secretion and enhanced by pentagastrin-evoked stimulation of gastric acid secretion. These data indicate that endogenous acid modulates the sensory gain of acid-sensitive vagal afferents. Further consistent with a role of these neurons in gastric nociception is the finding that exposure to proinflammatory cytokines and the induction of experimental gastritis or gastric ulceration sensitizes vagal afferent pathways to gastric acid. Taken together, these observations are of relevance to the understanding and treatment of gastric hyperalgesia and dyspeptic pain.
胃酸是与消化性溃疡及其他酸相关疾病（包括功能性消化不良）所致疼痛有关的一个因素，因为抗分泌治疗是上腹部疼痛治疗的主要手段。然而，胃化学性伤害感受的分子传感器、传入通路及中枢处理系统却鲜为人知。本文综述了新出现的证据，即迷走传入通路在胃化学性伤害感受中起关键作用。基于c-fos的快速表达，通过功能神经解剖学观察发现，大鼠胃黏膜暴露于腔内酸的反向扩散浓度时，信号会传至脑干，而非脊髓。迷走神经切断术可抑制对胃酸刺激的内脏运动反应，而内脏神经切除术则无此作用，这一发现补充了上述观察结果。抑制胃酸分泌可减少胃酸诱导的脑干c-fos表达，而胃泌素五肽诱发的胃酸分泌刺激则可增强该表达。这些数据表明，内源性酸可调节酸敏感迷走传入神经的感觉增益。与这些神经元在胃伤害感受中的作用进一步一致的是，暴露于促炎细胞因子以及诱导实验性胃炎或胃溃疡会使迷走传入通路对胃酸敏感。综上所述，这些观察结果与理解和治疗胃痛觉过敏及消化不良性疼痛相关。
