Central processing of vagal afferent input from the acid-injured rat stomach: Implications for dyspepsia?

Abstract

Background: Although gastric acid is a factor in upper abdominal pain caused by gastro-oesophageal reflux, gastritis, peptic ulcer and functional dyspepsia, the processing of a gastric mucosal acid insult within the central nervous system is little known. This study examined which neurons in the brain respond to challenge of the rat gastric mucosa by a noxious concentration of hydrochloric acid (HCI) and whether the central input is carried by vagal afferent neurons. Methods: Activation of central neurons was mapped via transcription of c-fos messenger ribonucleic acid (mRNA) and visualized by in situ hybridization autoradiography with a c-fos oligodesoxyribonucleic acid probe. Quantitative results were obtained by counting the number of c-fos mRNA-positive cells in 2: 5 sections (10 pm). Results: When examined 45 min after intragastric treatment of rats with HCI (0.5 M), many neurons in the nucleus of the solitary tract, lateral parabrachial nucleus, thalamic and hypothalamic paraventricular nucleus, supraoptic nucleus, central amygdala and habenula expressed c-fos mRNA as compared to intragastric treatment with saline. Some expression of c-fos mRNA was also noted in the area postrema and subfornical organ. Intragastric treatment with hypertonic saline (0.5 M) caused some expression of c-fos mRNA in medullary and hypothalamic nuclei, but the response to 0.5 M saline was only 10 30 % of that to 0.5 M HCI. The c-fos mRNA reaction to intragastric HCI in all regions was depressed by 2: 80 % five days after bilateral subdiaphragmatic vagotomy, whereas the number c-fos mRNA-positive cells in the periaqueductal grey and dorsal raphe nucleus was enhanced. Conclusions: These data show that acid-sensitive vagal afferents signal gastric acid challenge to the brainstem wherefrom the information is communicated to higher relay centres of the brain. The central processing of gastric mucosal acid insults involves nuclei that play a role in perception and in the regulation of behavioral, neuroendocrine, autonomic and antinociceptive reactions. It is anticipated that the findings have a bearing on the understanding of dyspeptic complaints. This study was supported by FWF grant P1l834-MED.