Luminal serotonin time-dependently modulates vagal afferent driven antinociception in response to colorectal distention in rats

被引:16
作者
Zhang, L. Y. [1 ]
Dong, X. [1 ]
Liu, Z. L. [1 ]
Mo, J. Z. [1 ]
Fang, J. Y. [1 ]
Xiao, S. D. [1 ]
Li, Y. [2 ]
Chen, S. L. [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gastroenterol,Shanghai Inst Digest Dis, Shanghai 200001, Peoples R China
[2] City Univ Hong Kong, Dept Biol & Chem, Hong Kong, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
5-hydroxytryptamine type 3 receptors; serotonin; vagal afferents; visceral pain; PARACRINE SUBSTANCE; RECEPTORS MEDIATE; 5-HT3; RECEPTORS; NOCICEPTION; SYSTEM; MODEL; ACTS;
D O I
10.1111/j.1365-2982.2010.01589.x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background Compelling evidence shows that vagal afferents mediate antinociception in response to visceral insults. Our recent findings implied that luminal serotonin (5-hydroxytryptamine, 5-HT) might mediate chronic food allergen sensitized visceral hyperalgesia, in which vagal afferents might be implicated. Here, to test this hypothesis, we investigated the effects of luminal infused 5-HT on visceral nociception and the involvement of vagal antinociceptive pathway. Methods The vagus-intact or vagotomized rats were given acute intraluminally or intraperitoneally administered 5-HT, or chronic luminal infusion of 5-HT. The visceromotor response (VMR) to colorectal distension (CRD) was electrophysiologically recorded. Key Results Acute intraluminal infusion of 5-HT (10 or 100 nmol) significantly attenuated VMR to CRD, while systemic administered 5-HT at similar doses resulted in markedly augmented nociception. Pretreatment with luminal application of granisetron or lidocaine, or pharmacological depletion of endogenous 5-HT with injection of p-chlorophenylalanine, a 5-HT synthesis inhibitor, and subdiaphragmatic vagotomy or functional deafferentation with capsaicin abolished the effect of luminal (but not systemic) 5-HT. Chronic infusion of 5-HT (10 nmol d-1for 5 days) produced gradual augmentation of baseline VMR. And, the VMR to CRD after 5-HT infusion decreased on day 1 and 2, then gradually increased from day 3. Surgical vagotomy or daily preperfusion with granisetron canceled these time-dependent patterns. Conclusions & Inferences Luminal 5-HT time-dependently modulates vagal afferent driven antinociception. Acute infusion of 5-HT attenuates visceral nociception via activation of vagal afferent 5-HT type 3 receptors (5-HT(3)Rs)within intestinal mucosa; while chronic luminal 5-HT caused gradually developed visceral hyperalgesia, which may also involve vagal 5-HT(3)Rs.
引用
收藏
页码:62 / E6
页数:9
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