Ulcer-like functional dyspepsia is a symptom complex characterized by epigastric discomfort, burning and/or abdominal pain at times associated with eating and often accompanied by belching, nausea and/or vomiting¹⁾. The origin of gastric pain has puzzled researchers and clinicians for over 60 years. The pathogenesis of functional dyspepsia is poorly understood and there are no clear guidelines for its treatment. Drugs that decrease gastric acidity have been used commonly for the symptomatic treatment of pain, but the results have been variable^2–7). Hypotheses regarding pathogenesis can be divided into two groups: those that ascribe it to a disturbance in gastric motillity and those that ascribe it to an imbalance in acid secretion^{8, 9)}. Infusing acid into the stomach of ulcer patients was reported to lead to gastric pain in early reports^10–12). However, later studies have failed to demonstrate pain despite infusion of large quantities of highly acidic solutions. Thus, the role of acid in eliciting gastric pain is less clear than was previously supposed. However, in recent reports, cimetidine has been found to be effective in providing symptomatic relief of pain in patients with ulcer-like functional dyspepsia^{6, 7)}, suggesting that symptoms in these patients may be related to gastric acid. There was no significant correlation between pain and acid secretion in functional dyspepsia. In order to test this hypothesis, we carried out a single blind cross over study to determine whether gastric acidification produced symptoms in patients with ulcer-like functional dyspepsia.

Most patients diagnosed as having dyspepsia do not have a chronic peptic ulcer or any recognized anatomicopathologic entity; thus, they are classified as having functional dyspepsia. As a working definition, especially patients with ulcer-like dyspepsia have symptoms that prompt a physician to believe an ulcer may be present, but no ulcer is found on evaluation¹³⁾. The prevalence of ulcer-like functional dyspepsia ranged from 20–30% and annual incidence of over 1%¹⁴⁾. It is at least twice as common as peptic ulcer disease. Ulcer-like functional dyspepsia is not only common but costly, because it often results in empric treatment intended to control gastric acidity including antacid or H₂ receptor blocker. Because treatment of this chronic disorder has been inadequate, studies of the pathogenesis are important. Peptic ulcer disease is considered to be closely related to gastric acid secretion. It has been postulated that acid oozing through altered mucosa produces abdominal pain¹⁵⁾. Two questions need to be considered : Is gastric acid secretion abnormal in ulcer-like functional dyspepsia, and does acid bathing of the mucosa ever cause symptoms? Gastric acid secretion was not increased in patients with ulcer-like dysyepepsia, and there were no differences in acid secretion between patients with typical ulcer-like functional dyspepsia¹⁶⁾. Most studies have confirmed that acid secretion is normal in patients with ulcer-like functional dyspepsia¹⁷⁾. In fact, negative correlation between peak acid secretion and severity of symptoms has been reported¹⁸⁾. It is uncertain if hydrochloric acid bathing of the mucosa causes symptoms, even in the presence of peptic ulcer. Early studies by Palmer and Pickering confirmed that duodenal ulcer pain is related to gastroduodenal acidity. Palmer¹⁰⁾ instilled acid into the stomach or duodenum in peptic ulcer patients whose last episode of pain occurred within the last 24 hours. Typical ulcer pain occurred in 314 out of 324 instances. Up to 600ml 0.5% hydrochloric acid (0.135N) was given. However, in some instances, it took more than one hour before pain occurred. Bonney and Pickering¹¹⁾ instilled up to 300ml 0.1N hydrochloric acid into the stomach of peptic ulcer patients during days when they experienced spontaneous ulcer pain. In eight out of nine cases, pain was reproduced. Pain was not induced by similar amounts of normal saline. Kang et al reported that 33% of patients with duodenal ulcer experienced pain during infusion of 10mmol of hydrochloric acid over five minutes. Of those who did not experience pain after the first 10mmol of acid, 21% developed pain when an additional 10mmol of acid was given¹⁹⁾.

In a study by Bates et al²⁰⁾, an injection of pentagastrin does lead to increased reports of epigastric pain in patients with non-ulcer dyspepesia. Misra²¹⁾ et al study showed that 22% of patients with non-ulcer dyspepsia developed pain on acid infusion. These patients did not develop pain during infusion with similar or even greater volume of saline, suggesting that pain was due to acidic pH and not due to volume distension of the stomach. Acid may be of importance in the genesis of symptoms in these patients as suggested by the pain induced due to acid infusion which was similar to the usual pain experienced by these patients. But, there are little data on direct instillation of acid in ulcer-like functional dyspepsia. In our study, 41.7% of the patients experienced pain during infusion of 0.1N of hydrochloric acid within five minutes. We included the patients with ulcer-like functional dyspepsia only. This explains why more of our patients experienced pain than others have reported under similar circumstances. The pathogenesis of ulcer pain in the remaining 58.3% of patients remains unclear. Altered gastroduodenal motility or spasm are other factors that may contribute to the pathogenesis of pain. Wilson²²⁾ had observed that pain in the duodenal ulcer was associated with sustained contraction of the duodenal bulb. Ruffin²³⁾ found that duodenal ulcer pain was invariably related to delay of gastric evacuation or spasm at the ulcer site. Texter⁸⁾ et al reported that ulcer pain was accompanied by increased intraluminal pressure and delayed emptying time, while relief of pain accompanied resumption of gastric evacuation. But these were, at most, minor factors and further studies are required in this area.

In conclusion, our findings suggest that gastric acid plays a role in the genesis of symptoms in some patients with ulcer-like functional dyspepsia, even though the clinical significance of these observation remains to be tested. Patients, in whom the pain is related to acid, may be expected to respond to treatment with H₂ receptor anatagonists. Obviously, a correlation of therapeutic efficacy of H₂ receptor anatagonists to the results of acid infusion would be interesting.