Can symptoms predict underlying pathophysiological mechanisms in functional dyspepsia?

incubation on polylysine/laminin coated coverslips for 10-16 hours in nerve growth factorsupplemented neurobasal medium, the nerve cell suspension was loaded with the calciumsensitive ionophore FURA-2.The coverslips were transferredto a perfusion chamber mounted on an inverted fluorescence microscope. Cells of gastric mucosal origin, identified by Texas red fluorescence were selectedfor further imaging. Cells were perfused with a pH7.4 HEPES buffer before being exposed to pH6.1 for 1 minute. After a further 10 minutes at pH7.4 the cells were exposed to 10TM Capsaicinfor 1 minute. Cell activation was identified by spikes in intracellularcalcium concentration using computerised image analysis (Ionvision, Improvisign). Results Cells staining positively for Texas red were observed only in the thoracic DRG of rats which lived for ->7 days post mucosal injections. There was a peak accumulation of labelled nerve cells which occurred at 2 weeks when 9+-2% (mean+-SEM)ofcells were Texas Red positive. Of these gastric derived nervecells 19+-6% respondedto both acid and capsaicin challenge as indicated by spikes in intracellular calcium concentration. In contrast, 38_+8% of unlabelledcells respondedto acid (p = 0.09). ConclusionA subpopulationof gastric mucosal nerve cells are acid and capsaicin sensitive and are likely to be the cells responsible for transmission of mucosal pain. Preliminaryresults suggestthat the proportion of cells sensitive to acid and capsaicin is less than that for somatic neurons suggestingan adaption to mucosal acid exposure.

effect of nociceptive stimulation of the peritoneum on the solid gastric emptying is, at least in part, due to the reduced vagal activity.

429 Can Symptoms Predid Underlying PathophysiologinalMechanisms In Functional Dyspepsia? Jan Tack, Rat Bisschops, Toon Degreef, Benny Geypens,Jozef Janesens, Ctr for G I Research, Univ of Leuven, Leuven Belgium Recentstudies in functional dyspepsiahaveindicateda relationshipbetweenspecificsymptoms and underlying pathophysiologicalmechanisms,such as delayedgastric emptying, hypersensitivdy to gastric distention or impaired accommodationto a meal Attempts to target therapy at the underlying disordersbeve been hampered by the invasive nature of the investigations needed to identify them. The aimof the present study was to investigate whether dyspepsia symptom pattern can predict underlying pathophysiology.Method~ In 167 functional dyspepsia patients(53 men, meanage 40+-1), the severity (0-3, 0 = absent,3 = severe)of 8 symptoms (pain, fullness, bloating, early satiety, nausea, vomiting, belching, epigestric burning) was scored. All patients underwent a %-octanoic acid breath test to assess gastric emptying rate and a gastric barostat study to determine sensitivity to distension and meal-induced accommodation. Results were compared to normal ranges. Association of mechanisms and symptoms was analyzed by univadate analysis. The sensitivity and specificity of associated symptoms to predict underlying mechanismswas calculated. Results. Impaired accommodalion, present in 40% of the patients, was predicted by relevant or severe early satiety with sen~ and specificity of 81% and 52% respectively,and by weight loss with sensitivity and specificity of 65% and 52% respectively. Hypersensitivityto gastric distention, present in 34% of the patients, was predicted by relevantor severepain with sensitivity and specificity of 84% and 47% respectively, by belching with sensitivity and specificity of 74% and 43% respectivelyand by weight loss with sensitivity and specificity of 63% and 44% respectively. Oelayedgastric emptying, present in 26% of the patients, was predicted by relevantor severe postprandial fullness with sensitivity and specificity 85% and 29% respectively, by relevant or severe nauseawith sensitivity and specificity 75% and 36% respectivelyand by relevant or severe vomiting with sensitivity and specificity of 44% and 40% respectively.Combining different symptoms did not substantiallyimprove sensitivity or specificity to predict underlying mechanisms. Conclusion.Symptompattern lacks the specificity to adequatelypredict underlying pathophysiologicalmechanisms in functional dyspepsiapatients. Studiestargeting therapy at the underlying disorder in dyspepsia require pathophysiological testing to identify the appropriate patient population.

427 The Afferent Pathway and Neurotransmittor After Acid Stimulation in gm Rat's Stomach Chino-Llano Lu, Div Gastroenterology,Taipei Veterans Gen Hosp, Taipei Taiwan Roc; KuoChi Chen, Oept of Anatomy, Yang-Ming Univ, Taipei Taiwan Roc; Fug-Young Chang, ShouDong Lee, Div gastroenterology,Taipei Veterans Gee Hosp, Taipei Taiwan Roc BACKGROUND:Acid play an important role in the pathogenensisof visceral pain in functional dyspepsia or peptid ulcer disease. The extrinsic afferent nerve fibers supplying the stomach arise from two different sources, Le., the spinal and vagal pathways. The definite route and neurotransmitter for the acid stimulation in the stomach is still not clear. This study set out to investigatethe pathways and neurotransmiffer by which gastric acid challengeis signaled to the brain. METHODS:After fasting for 16 hours, the rats were challengedwith HCL (0.7 mole/Li^or normal saline into the stomach according to their body weight (10 mliEkg-'. Then the animals were sacrificed at different time intervalsi]l, 4, and 24 hoursi to remove spinal cord (T8-TIO) and brain stem. Immunohistochemistry was used to measure the expression of c-los as well as substance P in the spinal cord and brain stem. RESULTS:(1)Significant inflammation was seen in the rats stomach after the acid instillation. And all rats became immobile after the instillation. (2) In spinal cord, acid instillation to the stomach induced a significant increase in the number of c-los immunoreactive (IR) nuclei when compared with controls, especially at T8 level (at 1 hour, 44.6_+3.7 VS. 8.8+-2.6 noJsection, pO.O5), The c-los IR cell mainly located in area postrema and nucleus tractus solitadi. (4) The optical density of substance P in the brain stem decreasedgradanlly after the acid stimulation and returned toward normal after 24 hour. (1 hr vs. 4 hr vs. 24 hr. 13.2_+2.4vs. -35.3+-3,1 vs 5.3_+1.0 %, P
43O

Effects Of Upl~ On Vizceral Perception And Gastric Relaxation In Functional

O~ema

Einar S. Gjomsson, Jonna Sjoberg, Gisela Ringstrom, Malte Norstrom, Magnus Simren, Hasse Abrahamsson, Dept of Internal Medicine, Gothenburg Sweden Background: Gastric hypersensitivity to mechanical stimulation and impaired accomodation of the proximal stomach to a meal have been reported in functional dyspepsia (FD). Our aim was to elucidate the relative importance of nutrients on perception thresholds (PTs) and gastric relaxation in FD patients, and compare patients with ulcer-like (ULD) and motility-like dyspepsia (MLD). Methods: 13 healthy volunteers and 20 patients with functional dyspepsia (FD) according to the Rome II criteria were studied, 10 ULD and 10 MLD. A feeding tube was placed fluoroscopically in the proximal duodenum and a harostat balloon was placed in the proximal stomach. PTs for first sensation, bloating and discomfort were assessed before and after duodenal lipid infusion (2 kcal/min, 60 min). Volume changes in the balloon were recorded as a measure of gastric tone. Results: Perception thresholds (PTs) were lower in patientswith FDthan in controls for bloating (t 3 + 1 vs. 16+-O.6mmHg;p
428 Nooiceptive Stimulation Of The Peritoneum inhibits Antro-Pyloric Coordination And Delays Gastric Emptying Via Reducing Vagal Tone In Conscious Rats. Lok Yon Sung, Llniv of Michigan, Ann Arbor, MI; Tadashi Ishiguchi, WakayamaMedical Coil Kihoku Hosp, WakayamaJapan; Hitoshi Tada, Toku Takahashi, Duke Univ Medical Ctr, Durham, NC Background: it has been demonstratedthat nociceptivestimulation of the peritoneum inhibits gastrointestinal(GI) motility. To investigatethe inhibitory mechanismof nociceptivestimulation of the peritoneum on GI motility, we studied the effects of intraperitoneal (i.p.) injection of hydrochloricacid (HCl) on solid gastric emptying and postprandialgastric motility in conscious rats. Methods: After 24 hr-fasting, rats were given preweighed pellets (1.5 g) for 10 rain. Food intake was measuredby weighing the uneaten pellets. Rats were sacrificed 90 min after the feeding and the gastric content was recovered from the stomach. Calculated gastric emptying was compared between rats received i.p.-injection of saline (0.5 ml; control) and HCI (0.1 M/O.5ml). To study postprandialgastric motility, two force transducerswere implanted on the antrum and pylorus. To investigate whether the inhibitory effect of HCI on gastric motility is mediated via vagal pathway, sham feeding-inducedgastric motility was compared betweensaline- and HCI-inlectadrats. Results; i.p.-injection of HCI almost completely blocked the solid gastric emptying (3+-1%), compared to controls (63_+5%, P
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