Desensitization of Capsaicin-Sensitive Sensory Neurons in Rat Stomachs on Chronic Treatment with Sodium Taurocholate

Abstract

ABSTRACT-We examined the effects of chronic treatment with 10 mM sodium taurocholate (TC) on gastric functions, capsaicin-sensitive afferent neurons and the gastric mucosa in male rats. Stomachs were mounted in Lucite chambers, and then the transmucosal potential difference (PD), luminal pH and gastric mucosal blood flow (GMBF) in response to TC or capsaicin was determined. In normal animals, 10 mM TC caused a reduction in PD, and increases in luminal pH and GMBF. Capsaicin (1 mg/ml) produced an apparent increase in GMBF without any change in PD or luminal pH. After 4-or 12-week treatment with TC, the basal PD was significantly reduced, and the luminal pH tended to increase. The increase in GMBF in response to TC or capsaicin was profoundly suppressed in TC-pretreated animals. The calcitonin generelated peptide release in response to capsaicin was significantly reduced after 4 weeks treatment with TC. There were no microscopical changes in the oxyntic mucosa until 4 weeks after TC treatment except for exfoliation of surface cells. However, an increase in inflammatory cell infiltration was observed 12 weeks later. We conclude that chronic treatment with TC causes desensitization of capsaicin-sensitive afferent neurons and reduces GMBF, which may result in the production of gastritis.Keywords: Gastritis, Sodium taurocholate, Capsaicin-sensitive afferent neuron, Calcitonin gene-related peptide, Gastric mucosal blood flow Chronic treatment with 5 mM sodium taurocholate (TC) for >3 months induces gastritis in rats (1, 2). We also observed that treatment of rats having undergone unilateral vagotomy with 5 mM TC for 6 months induced gastritis that involved decreases in the number and density of parietal cells and an increase in inflammatory cell infiltration (3). The mechanism by which chronic treatment with TC results in such gastritis remains unclear. There is increasing evidence that capsaicin-sensitive afferent neurons (capsaicin-sensitive neurons) participate in the protective mechanism against acute gastritis or gastric ulceration (4-7), probably through the release of the calcitonin gene-related peptide (CGRP) (8 -10). Therefore, it is possible that acute or chronic depletion of CGRP from the gastric or duodenal mucosa may weaken the mucosal integrity, leading to the production of gastritis and ulcers. Indeed, ulcerogens such as acetic acid, concentrated ethanol and cysteamine significantly depleted CGRP from the peripheral endings of capsaicin-sensitive neurons, suggesting a causal relationship (11-13). It was of interest to examine whether or not chronic treatment with TC has any damaging effect on capsaicin-sensitive neurons which leads to disturbance of gastric functions, thereby eventually resulting in the production of gastritis. In this study, we determined the changes in gastric functions, the amount of CGRP released from the gastric mucosa and gastric mucosal histology in TC-treated animals. An abstract of part of this study has already been published (14). MATERIALS AND METHODS AnimalsMale Donryu rats ...

Does Helicobacter pylori-induced inflammation of gastric mucosa determine the severity of symptoms in functional dyspepsia?

“…Previously, it has been reported that gastric infl ammation associated with alkaline refl ux was partly associated with desensitization of capsaicin-sensitive afferent neurons by bile. 35 Additionally, capsaicin, a component of red pepper, has been found to be effi cacious in patients with functional dyspepsia, probably through a desensitization of afferent neurons. 36 In one study, evaluation of jejunal specimens of patients with irritable bowel syndrome showed preganglionic infl ammation and neuronal degeneration in Histopathology scores…”

Capsaicin and Gastric Ulcers

“…Investigations have been made using invivo stomach, 21 stomach mounted in ex vivo chamber preparations, [22][23][24][25][26][27][28][29][30]32,35,120 stomach chambered with the blood supply intact, 33 glandular stomach of anesthetized rats chambered between two plastic rings, 34 perfused duodenum of anesthetized rats or duodenal loop of rats 23,42 and conscious dogs with duodenal loops and Heidenhain pouches. 44 The administration of capsaicin, various noxious agents, and the assay of certain gastric constituents have been made using rats, dogs, and cats with gastric fistula and gastric cannula, 45−49 anesthetized rats and chronically implanted gastric and duodenal cannula, 50,51,189 awake male beagle dogs with a chronic intra cerebro ventricular (i.c.v) cannula and gastric fistula 52 and anesthetized rats fasted overnight with acutely cannulated cisterna magna.…”

“…86,93 The length and surface area of injury has been measured by planimetry 31,46,89 and by computerized image analysis. 93 The transmucosal potential difference (pd) followed as an indication of surface epithelial injury 24,27,29,34,38,42,94 has been measured by mounting the tissue in an Ussing chamber perfusion system. The undamaged mucosa maintained a pd of about −64 mv in both control and after calcitonin gene-related peptide (CGRP) treatment.…”

“…does not cause any damage to the stomach wall as judged by light and SEM. 37 It is found not to influence the transmucosal pd, 29,35,37,135,165 an indication of mucosal disruption 121 or pH of the stomach 29,35 unlike the mild irritants 0.5, 0.75 and 1M NaCl 27,266 and the noxious agents aspirin 38 and sodium taurocholate. 29 which cause mucosal injury and alter pd.…”

Enhanced Gastric Mucosal Damage in Rats after Chronic Treatment with Sodium Taurocholate

“…We reported that chronic administration of 10 mM sodium taurocholate (TC) to rats for > 4 weeks apparently desensitized capsaicin-sensitive afferent neurons (capsaicin-sensitive neurons) in the gastric mucosa, as evidenced by the reduced release of calcitonin gene-related peptide (CGRP) (1). Since chronic treatment with TC induces erosive or atrophic gastritis (2, 3), we proposed that the desensitization of capsaicin-sensitive neurons is one of the causal factors for such pathologic changes.…”