**1. Introduction**

182 Gastrointestinal Endoscopy

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According to the Rome ІІІ classification, functional gastroduodenal disorders (FGIDs) in adults are subdivided into six domains. Functional dyspepsia (FD) is a subcategory of the FGIDs. It is characterized by the presence of symptoms that are believed to be associated with gastroduodenal lesions, particularly epigastric pain or burning, postprandial fullness, or early satiation, without the evidence of organic disease to explain the onset of these symptoms at least 6 months before diagnosis (Tach J et al., 2006). Furthermore, FD is divided into 2 subtypes postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). The diagnostic criteria for PDS include the presence of 1 or both of the following symptoms several times in a week: bothersome postprandial fullness occurring after ordinary-sized meals, and early satiation that prevents finishing a regular meal. The diagnostic criteria for EPS include the presence of all of the following symptoms: moderately severe pain or burning localized to the epigastrium at least once per week, and intermittent pain, not generalized or localized to other abdominal or chest regions, not relieved by defecation or passage of flatus, and not fulfilling the criteria for gallbladder and sphincter of Oddi disorders.

FD is a functional disorder that affects 10-30% of the population worldwide. The results of an Itarian population-based study, indicated that the prevalence rates of FD were 11%. Of these, PDS, EPS, and PDS accompanied with EPS were 67.5%, 48.2%, and 15.8% respectively (Zagari RM et al.,2010).The results of a Swedish population-based study, indicated that the prevalence rates of FD, PDS, EPS, and PDS accompanied with EPS were 15.7%, 12.2%, 5.5%, and 1.7%, respectively (Aro P et al., 2009). The results of a Norwegian population-based study, showed that the lifetime prevalence rate of FD was 23% in men and 18% in women (Johnsen et al., 1988), and that in the United States, was 29% (Shaib Y et al., 2004).

<sup>\*</sup> Hiroaki Kusunoki2, Noriaki Manabe3, Tomoari Kamada1, Ken-ichi Tarumi1, Hiroshi Matsumoto1, Motonori Sato1, Yoshiyuki Yamanaka1, Takahisa Murao1, Hideaki Tsutsui1, Akiko Shiotani1, Jiro Hata3, and Ken Haruma1

<sup>1</sup>*Division of Gastroenterology department of Internal Medicine,* <sup>2</sup>*Division of General Medicine* <sup>3</sup>*Division of Endoscopy and Ultrasound Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Kurashiki, Japan*

Evaluation of Duodenal Hypersensitivity to Acid Using Transnasal Endoscopy 185

mediating signals for the noxious stimulation of the stomach. Further, Scicho *et al.* (2005) reported that gastric acidification increased the expression of phosphorylated extracellular signal-regulated kinase-1 and -2 (p-ERK1/2) in the dorsal root ganglion neurons via *N*methyl-D-aspartate receptors. They suggested that sympathetic pathways are involved in mediating signals for noxious stimulation of the stomach. Noxious mechanical stimulation showed that most of the increased p-ERK1/2 neurons coexpressed transient receptor

Transient receptor potential vanilloid receptor 1 and the acid-sensing ion channel 3 are largely involved in the acid-induced nociception in mammals (Ugawa *et al.*, 2002), but it is still unknown which receptors of the peripheral sensory pathways encode and integrate an acidinduced nociceptive event in the gastric mucosa and the duodenal mucosa. Akiba *et al.*  (2002) reported that the capsaicin pathway is an acid-sensing pathway that promotes

potential vanilloid receptor 1 and acid-sensing ion channel 3 (Sakurai *et al.*, 2008).

hyperemia and mucus secretion in response to luminal acid in the duodenum.

acidification using transnasal endoscopy (Ishii *et al.*, 2008).

VAS

\*

Analogue Scale

\* \* \* \*

Pure Water Acid

**2.4 Method for evaluating duodenal hypersensitivity to acid and gastric motility**  Duodenal hypersensitivity to acid is one of the more important factors in the pathogenesis of FD. Although manometric methods, scintigraphic methods, electrogastrography and ultrasonography have been used to evaluate enterokinesis, a practical method for evaluating duodenal hypersensitivity to acid has not been reported. Transnasal endoscopy is a rescently developed, non-invasive and nondiscomforting method for examination of the upper gastrointestinal tract (Yagi *et al.*, 2005; Murata *et al.*, 2007). We developed a new method for evaluating duodenal hypersensitivity to acid and gastric motility by duodenal

0 2 4 6 8 10 12 14 16 18 20

VAS VAS VAS VAS VAS VAS VAS VAS VAS VAS

Time(min)

\* \* \* \*\*\*\*\*\*\*

\*\*

Fig. 1. \*Number of antral contractions every two minutes; \*\*Motility number; VAS: Visual

The study protocol is shown in Fig. 1. All subjects underwent transnasal endoscopy as required in the left lateral decubitus position in the morning after overnight fasting. The infusion of air into their stomachs was minimized in order to observe their gastric motility. An infusion tube (outer diameter 1.5 mm) was then introduced by transnasal endoscopy until the tip was located in the duodenal bulb. The subjects changed their body position to the supine position, and their antral contractions and dyspeptic symptoms were evaluated before and after a duodenal infusion of pure water (36.5°C, 100 ml) and acid (36.5°C, 0.1 N

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