Antinociceptive property of tegaserod in a rat model of chronic visceral hypersensitivity.
OBJECTIVE
To establish a model of chronic visceral hypersensitivity in rats and to investigate the effect of tegaserod, a partial 5-hydroxytryptamine-4 receptor agonist, on visceral hypersensitivity.


METHODS
Neonate Sprague-Dawley rats at 8-21 days after birth underwent colorectal distension once daily. Adult rats aged 8-10 postnatal weeks underwent colorectal distension and the abdominal withdrawal reflex (AWR) during the distension was determined. The AWR score was recorded before and after intraperitoneal administration of either tegaserod (treatment group: 0.3 mg/kg) or vehicle (control group).


RESULTS
Changes in the AWR score were dependent on the pressure intensity of the colorectal distension (P < 0.01). At pressures of 40, 60 and 80 mmHg, the AWR scores in the model rats with visceral hypersensitivity were significantly higher than those recorded in the control group (1.95 +/- 0.16 vs 1.35 +/- 0.15, 2.82 +/- 0.12 vs 2.17 +/- 0.13, 3.20 +/- 0.14 vs 2.59 +/- 0.14, P < 0.01). Compared with the controls, tegaserod significantly decreased the AWR scores at the distension pressures of 40, 60 and 80 mmHg (1.95 +/- 0.50 vs 1.32 +/- 0.55, 3.05 +/- 0.48 vs 2.32 +/- 0.54, 3.25 +/- 0.63 vs 2.77 +/- 0.51, P < 0.05).


CONCLUSIONS
Adult rats can develop chronic visceral hypersensitivity after transient colorectal mechanical irritation during their postnatal period. Tegaserod increases the pain threshold to noxious stimuli, suggesting an antinociceptive property in its effect on visceral hypersensitivity.
Liang
Lie Xin
LX
Division of Gastroenterology of Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, Wuhan, China.
Zhang
Qing
Q
Qian
Wei
W
Hou
Xiao Hua
XH
D000818:Animals; D000831:Animals, Newborn; D003108:Colonic Diseases / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology* / Q000662:veterinary; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012002:Rectal Diseases / Q000188:drug therapy / Q000503:physiopathology / Q000662:veterinary; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D007211:Indoles; D017366:Serotonin Receptor Agonists; C105050:tegaserod