title: Luminal serotonin time-dependently modulates vagal afferent driven antinociception in response to colorectal distention in rats.
abstract: 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.
  
  
  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(-1) for 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
  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.
authors: Department of Gastroenterology, Renji Hospital, Shanghai Institute of Digestive Disease, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: L Y
authors: LY
authors: Zhang
authors: X
authors: X
authors: Dong
authors: Z L
authors: ZL
authors: Liu
authors: J Z
authors: JZ
authors: Mo
authors: J Y
authors: JY
authors: Fang
authors: S D
authors: SD
authors: Xiao
authors: Y
authors: Y
authors: Li
authors: S L
authors: SL
authors: Chen
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003106:Colon / Q000294:innervation / Q000503:physiopathology*; D004108:Dilatation, Pathologic; D005512:Food Hypersensitivity / Q000503:physiopathology; D017829:Granisetron / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects*
chemical_list: D000700:Analgesics; D002211:Capsaicin; D017829:Granisetron; D008012:Lidocaine; D012701:Serotonin; D012702:Serotonin Antagonists