2021 Fiscal Year Final Research Report
Central mechanism of visceral sensation with special reference to brain orexin and its clinical application for irritable bowel syndrome
| Project/Area Number |
19K08410
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 53010:Gastroenterology-related
|
|---|
| Research Institution | Asahikawa Medical College |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
高草木 薫 旭川医科大学, 医学部, 教授 (10206732)
野津 司 旭川医科大学, 医学部, 教授 (30312367)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | グレリン / オレキシン / オキシトシン / 脳 / 内臓知覚 / ラット / オピオイド / ドパミン |
|---|
| Outline of Final Research Achievements |
Visceral hypersensitivity is a major pathophysiology in irritable bowel syndrome (IBS). Little had been known how brain controls visceral sensation. To improve therapeutic strategy in IBS, we should develop a novel approach to control visceral hypersensitivity. Orexin, ghrelin or oxytocin in the brain is capable of inducing visceral antinociception. Dopamine, cannabinoid, adenosine or opioid in the central nervous system (CNS) plays a role in the visceral hyposensitivity. Central ghrelin could induce visceral antinociception via the orexinergic signaling. Orexin induces visceral antinociception through oxytocin. From these evidence, we would like to make a hypothesis that orexin signaling in the brain may play a role in the pathophysiology in a part of patients with IBS who are frequently accompanied with visceral hypersensitivity. We would suggest that modified orexin signaling may lead a novel therapeutic option for IBS.
|
| Free Research Field |
消化器内科
|
| Academic Significance and Societal Importance of the Research Achievements |
過敏性腸症候群(IBS)の主要病態に内臓知覚過敏がある．この発症メカニズムを解明し，病態を改善してIBSの治療を目指すことは合理的である．我々はオレキシンを中心とする内臓知覚調節の中枢メカニズムを網羅的に研究中である．神経ペプチド オレキシンやグレリン、オキシトシンは中枢神経系に作用して脳内ドパミン，アデノシンやカンナビノイド、オピオイド神経系を介して内臓知覚を鈍麻させることが明らかになった．グレリンやオキシトシンによる作用はオレキシン神経経路を利用することも明らかになった。脳内オレキシン神経を中心としたネットワークを刺激・活性化することで、内臓知覚を改善しIBSが治療できる可能性がある。
|
