Contribution of capsaicin-sensitive afferent nerves to rapid recovery from ethanol-induced gastric epithelial damage in rats.
OBJECTIVE
It is well known that capsaicin-sensitive nerve signaling acts as a protective factor against various ulcerogens. However, the contribution of topical capsaicin-sensitive nerves within the stomach to rapid restitution has not been fully investigated. The present study was therefore conducted focusing on recovery from gastric mucosal damage induced by ethanol in vivo.


METHODS
Male Sprague-Dawley rats were fasted and anesthetized. 51Cr-EDTA was administered intravenously and gastric mucosal integrity was continuously monitored by measuring the blood to lumen 51Cr-EDTA clearance. Capsaicin or vehicle was irrigated before, together with or after the perfusion of 20% ethanol, followed by perfusion with saline. In another experiment, ruthenium red, a capsaicin-sensitive cation antagonist, was given before the ethanol-capsaicin perfusion. Furthermore, this study was verified using lafutidine, a histamine H2-receptor antagonist, which has a gastric mucosal protective action through the capsaicin-sensitive afferent nerves.


RESULTS
When capsaicin was administered before ethanol treatment, mucosal damage was significantly reduced and recovery was significantly rapid compared to the control. When capsaicin (160 micro M) and ethanol were administered simultaneously, the mucosal damage was exacerbated but recovery was nevertheless more rapid than the control group. With a lower dose of capsaicin (80 micro M), mucosal damage was not exacerbated and recovery was enhanced. When capsaicin or lafutidine was administered after the induction of ethanol injury no change was detected regarding the damage. However, recovery was significantly accelerated. Ruthenium red reversed the action of post-treatment with capsaicin on restitution.


CONCLUSIONS
These results indicate that luminal administration of capsaicin exerts protection against and accelerates restitution from gastric damage in the very early phase after ethanol injury. This action is probably due to activation of topical capsaicin-sensitive afferent nerves in the rat.
Sobue
Masashi
M
First Department of Internal Medicine, Nagoya City University Medical School, Nagoya, Japan.
Joh
Takashi
T
Oshima
Tadayuki
T
Suzuki
Hideo
H
Seno
Kyoji
K
Kasugai
Kunio
K
Nomura
Tomoyuki
T
Ohara
Hirotaka
H
Yokoyama
Yoshifumi
Y
Itoh
Makoto
M
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002199:Capillary Permeability; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004492:Edetic Acid; D000431:Ethanol; D005753:Gastric Mucosa / Q000098:blood supply / Q000294:innervation* / Q000473:pathology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red / Q000494:pharmacology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology
D000081:Acetamides; D000897:Anti-Ulcer Agents; D010880:Piperidines; D011725:Pyridines; D012430:Ruthenium Red; D000431:Ethanol; C076948:lafutidine; D004492:Edetic Acid; D002211:Capsaicin