Ramosetron decrease visceral pain hypersensitivity in young rats

Abstract

Abstract: AIM: To explore the effects of 5-HT3 receptor antagonist ramosetron on young rats of visceral hypersensitivity by the methods of behavior and electrophysiology research. METHODS: Colorectal irritation (CI) stimulation in neonatal period was used to establish the model of visceral hypersensitivity in young rats. 32 neonatal rats were divided into four groups by 2×2 factorial design with each 8. Group A₁B₁ was imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection in 15-21 day; Group A₁B₂ was imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection; Group A₂B₁ was not imposed on CI at neonatal period and imposed on ramosetron intraperitoneal injection; Group A₂B₂ was not imposed on CI at neonatal period and not imposed on ramosetron intraperitoneal injection. Then, conventionally breeding till the young period (6-week age), abdonminal withdrawal reflex (AWR), pain thresholds and spike external oblique muscle of abdomen (EOMA) were used to evaluate visceral pain hypersensitivity. RESULTS: he pain thresholds in young rats were affected both by CI at neonatal period and using ramosetron in 15-21 days. In group A₁B₂ which imposed on CI at neonatal period, the pain thresholds decreased 11.56 mm Hg. In group A₁B₁ which imposed on CI at neonatal period and imposed on ramosetron in 15-21 day, the pain thresholds increased 9.06 mm Hg, while the AWR scores and EOMA were decreased. Future more, there are interaction effects between the two factors.There were a significant main effect for AWR scores at different pressures and a significant main effect for EOMA at different pressures. CONCLUSION: 5-HT₃ receptor antagonist ramosetron can decrease visceral hypersensitivity in young rats.

Key words: Visceral pain hypersensitivity, 5-HT₃ receptor antagonist, Ramosetron, Young rats

CLC Number:

R965.2

LIN Xi, YANG Fang, WU Bin, ZHANG Xiaoyan, LIN Chun. Ramosetron decrease visceral pain hypersensitivity in young rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(10): 1102-1107.

References

[1] 李定国,周惠清,宋艳艳,等. 全国城市中小学生肠易激综合征现况调查[J]. 中华内科杂志,2007,6(2):99-102.
[2] Al-chaer ED,Kawasaki M,Pasricha PJ. A new model of chronic visceral hypersensitivity in adu1t rats induces by colon irritation during postnata1 development[J]. Gastroentero,2000,119(5):1276-1285.
[3] Hirata T,Keto Y,Nakata M,et al.Effects of serotonin 5-HT3 receptor antagonists on stress-induced colonic hyperalgesia and diarrhoea in rats: a comparative study with opioid receptor agonists, a muscarinic receptor antagonist and a synthetic polymer[J]. Neurogastroenterol Motil,2008, 20(5):557-565.
[4] Vanhatalo S,van Nieuwenhuizen O. Fetal pain[J]? Brain Dev, 2000, 22(3): 145-150.
[5] Anand KJ,Coskun V,Thrivikraman KV,et al.Long-term behavioral effects of repetitive pain in neonatal rat pups[J]. Physiol Behav,1999,66(4):627-637.
[6] 吴斌,张睿,林国威,等. 新生期结直肠刺激对幼鼠腹外斜肌放电及脊髓Fos蛋白表达的影响[J]. 中华围产医学杂志,2008,11(5):338-342.
[7] Roozendaal B,Okuda S,VanderZee EA,et al. Glucocorticoid enhancement of memory requires arousal-induced noradrenergic activation in the basolateral amygdale[J]. Proc Natl Acad Sci USA,2006,103(17):6741-6746.
[8] Mawe GM,Coates MD,Moses PL.Review article: intestinal serotonin signalling in irritable bowel syndrome[J]. Aliment Pharmacol Ther,2006,23(8):1067-1076.
[9] Hirata T,Keto Y,Funatsu T,et al.Evaluation of the pharmacological profile of ramosetron, a novel therapeutic agent for irritable bowel syndrome[J]. J Pharmacol Sci,2007,104(3):263-273.
[10] Matsueda K,Harasawa S,Hongo M,et al.A phase II trial of the novel serotonin type 3 receptor antagonist ramosetron in Japanese male and female patients with diarrhea-predominant irritable bowel syndrome[J]. Digestion,2008,77(3/4):225-235.
[11] Suzuki R,Morcuende S,Webber M,et al.Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways[J]. Nat Neurosci. 2002,5(12):1319-1326.
[12] Laporte AM,Koscielniak T,Ponchant M,et al.Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I]iodo-zacopride and [3H]zaco-pride as radioligands[J]. Synapse,1992,10(4):271-281.
[13] Miura M,Lawson DC,Clary EM,et al.Central modulation of rectal distension-induced blood pressure changes by alosetron, a 5-HT3 receptor antagonist[J]. Dig Dis Sci,1999,44(1):20-24.