2007 Fiscal Year Final Research Report Summary
Mechanisms of stomach pain in organic and functional dyspepsia
| Project/Area Number |
18613004
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pain science
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| Research Institution | Nagoya University |
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Principal Investigator |
OZAKI Noriyuki Nagoya University, Graduate School of Medicine, Associate Professor (40244371)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIURA Yasuo Nagoya University, Graduate school of Metlicine, Vice President (50093042)
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| Project Period (FY) |
2006 – 2007
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| Keywords | visceral pain / functional dyspepsia / stress / CRF / ASICs / gastric ulcer / nerve growth factor / ATP |
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| Research Abstract |
Aim of Investigation: Gastric hyperalgesia may be involved in organic and functional dyspepsia (pain and discomfort). In this study, we investigated the mechanisrns of gastric hyperalgesia induced by either repeated water avoidance stress or .experimental ulcer using behavioral, histological and immunohistochemical methods.
Methods: Long Evans rats were subjected to repeated water avoidance stress (1 hr/day) for 7 days. Gastric ulcer was made by acetic acid injection into the stomach wall in Sprague-Dawley rats. Stomach sensitivities were assessed by recording EMG from acromiotrapezius muscle in response to gastric distension. Histological changes of stomach mucosa were examined by hematoxylin and eosin staining. The involvement of CRF, ASICs, NGF, and ATP in hyperalgesia was behaviorally evaluated.
Results: Repeated water avoidance stress induced increased response to gastric distension on day 8 and day 10 after the stress suggesting induction of gastric hyperalgesia. No histological changes were observed in the stomach wall. Gastric hyperalgesia was attenuated by systemic administration of either CRF antagonist α-Helical or ASICs antagonist amiloride. Acetic acid injection produced experimental ulcer in the stomach wall, and led to gastric hyperalgesia. Gastric hyperalgesia induced by acetic acid injection was attenuated by systemic administration of either neutralizing anti-NGF antibody P2X receptor antagonist PPADS or P2X_2,3,2,β specific antagonist A-317491.
Conclusions: Repeated water avoidance stress induced delayed onset gastric hyperalgesia without any mucosal lesion in the stomach. These results provide a new animal model to study functional dyspepsia. CRF and ASICs contributed to the stress-induced delayed gastric hyperalgesia. On the other bands, NGF and its receptor TrkA, ATP and its receptor P2X_2,3,2,β are engaged in the gastric hyperalgesia observed in animal with gastric ulcer
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