Sensory neuron-mediated gastric mucosal protection is blocked by cyclooxygenase inhibition.
BACKGROUND
Sensory neurons have been proposed to play a critical role in the protection of the gastric mucosa from a variety of necrotizing agents. The purposes of this study were (1) to investigate the effect of topical capsaicin, a sensory neuron stimulant, on the gastric mucosal injury caused by the topical application of low concentrations of bile acid and (2) to determine whether local neuronal blockade with topical lidocaine or cyclooxygenase blockade with systemic indomethacin has any effect during pretreatment with capsaicin.


METHODS
Before injury with topical 5 mmol/L acidified taurocholate (pH 1.2) rat stomachs were pretreated with either vehicle or capsaicin (160 mmol/L), both with and without prior administration of either lidocaine (1%) or indomethacin (5 mg/kg subcutaneously). Injury was assessed by measuring net transmucosal ion fluxes, the appearance of deoxyribonucleic acid into the gastric lumen, and gross and histologic injury scores.


RESULTS
Pretreatment with topical capsaicin significantly (p < 0.05) decreased bile acid-induced net luminal ion fluxes and luminal deoxyribonucleic acid accumulation, an effect blocked by both lidocaine and indomethacin.


CONCLUSIONS
Thus both local neuronal blockade and cyclooxygenase inhibition block the protective effect of capsaicin, findings corroborated by gross and histologic injury analysis. This study suggests that sensory neurons may mediate gastric mucosal protection from bile acid injury by increasing synthesis of endogenous prostaglandins.
Mercer
D W
DW
Reichle Research Laboratory, Department of Surgery, Temple University Hospital, Philadelphia, Pa.
Ritchie
W P
WP
Dempsey
D T
DT
D000287:Administration, Topical; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D009407:Nerve Block; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D016861:Cyclooxygenase Inhibitors; D013656:Taurocholic Acid; D004247:DNA; D008012:Lidocaine; D002211:Capsaicin; D007213:Indomethacin