title: Antinociceptive effect of berberine on visceral hypersensitivity in rats.
abstract: OBJECTIVE
  To assess the protective effect of berberine administration and the role of nitric oxide (NO) in visceral hypersensitivity.
  
  
  METHODS
  Fifty male Sprague-Dawley rats were randomly assigned to five groups. An inflammatory bowel disease model was induced in rats by intracolonic instillation of 1 mL 4% acetic acid at 8 cm proximal to the anus for 30 s and restraint stress. After subsidence of inflammation on day 7 of the experiment, the rats were subjected to rectal distension, performed by a balloon (6-Fr, 2 mm external diameter, disposable silicon balloon-urethral catheter for pediatric use) which was rapidly inflated with increasing volumes of prewarmed (37 °C) water (0.1, 0.2, 0.3, 0.4, 0.6, 0.8 and 1 mL) for 30 s at four-minute intervals, and then the abdominal withdrawal reflex (AWR) and the level of fecal output were measured, respectively. AWR scores either 0, 1, 2, 3 or 4 were obtained by blinded observers. Rats had been pretreated with berberine or aminoguanidine (NO synthetase inhibitor) or berberine + aminoguanidine before measurement.
  
  
  RESULTS
  The rats in the placebo group showed a hypersensitive response to rectal distension (2.69 ± 0.08 vs 1.52 ± 0.08, P = 0.000) and defecated more frequently than those in the control group (5.0 ± 0.16 vs 0.44 ± 0.16, P = 0.000). Comparing the berberine with placebo group, the AWR scores were reduced for all distension volumes and were significant at 0.2-1 mL (1.90 ± 0.08 vs 2.69 ± 0.08, P = 0.000), while the numbers of hard pellets, soft pellets, formless stools, and total fecal output in the placebo group were significantly larger than in the berberine group (5.0 ± 0.16 vs 2.56 ± 0.16, P = 0.000). Administration of aminoguanidine or berberine + aminoguanidine before VH score measurement reversed the antinociceptive effect of berberine (2.52 ± 0.08 vs 1.90 ± 0.08, P = 0.000; 2.50 ± 0.08 vs 1.90 ± 0.08, P = 0.000). The numbers of hard pellets, soft pellets, formless stool, and total of fecal output in aminoguanidine group were significantly larger than the corresponding values in control group, berberine group, and berberine + aminoguanidine group (4.81 ± 0.16 vs 0.44 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 2.56 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 3.75 ± 0.16, P = 0.000). The berberine and berberine + aminoguanidine groups showed reduced defecation, but aminoguanidine alone did not reduce defecation (2.56 ± 0.16 vs 4.81 ± 0.16, P = 0.000; 3.75 ± 0.16 vs 4.81 ± 0.16, P = 0.000).
  
  
  CONCLUSIONS
  Berberine had an antinociceptive effect on visceral hypersensitivity, and NO might play a role in this effect.
authors.affiliation: Department of Gastroenterology, 175 Hospital of PLA, Affiliated Southeast Hospital of Xiamen University, Zhangzhou 363000, Fujian Province, China.
authors.forename: Qing-Lin
authors.initials: QL
authors.lastname: Tang
authors.forename: Min-Ling
authors.initials: ML
authors.lastname: Lai
authors.forename: Yuan-Fu
authors.initials: YF
authors.lastname: Zhong
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Wang
authors.forename: Jun-Kai
authors.initials: JK
authors.lastname: Su
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Zhang
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D003672:Defecation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D059225:Nociception / Q000187:drug effects*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000187:drug effects* / Q000294:innervation
chemical_list: D000700:Analgesics; D001599:Berberine; D009569:Nitric Oxide; D019342:Acetic Acid
keywords: Berberine; Irritable bowel syndrome; Nitric oxide; Visceral hypersensitivity
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