The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients
The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients
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DOI：
10.1046/j.1365-2036.2002.01287.x
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发表时间：
2002-07-01
影响因子：
7.6
通讯作者：
Naliboff, BD
中科院分区：
文献类型：
--
作者：
Mayer, EA;Berman, S;Naliboff, BD
目的：开展一项安慰剂对照的功能性脑成像研究，以评估5-羟色胺-3受体拮抗剂阿洛司琼对肠易激综合征症状、直肠乙状结肠扩张引起的脑区域激活以及相关的感知和情绪反应的影响。方法：52例非便秘性肠易激综合征患者（28例女性）加入阿洛司琼（1- 4mg / d）的随机、安慰剂对照试验。37名患者在随机分组后完成了两次脑部扫描。直肠乙状结肠刺激用计算机控制的气压计进行。使用H (2) (15) O正电子发射断层扫描评估局部脑血流的变化。刺激等级和胃肠道症状的变化采用言语描述量表进行评估。结果：阿洛司琼治疗与症状评分和情绪刺激评分的降低有关，而不是安慰剂。与基线相比，阿洛司琼治疗与双侧额颞叶和各种边缘结构（包括杏仁核）的区域脑血流量减少有关。与安慰剂相比，阿洛司琼治疗后，杏仁核、腹侧纹状体、下丘脑和扣带回活性的降低明显更大。结论：在非便秘型肠易激综合征患者中，5-羟色胺-3受体拮抗剂治疗3周可降低大脑对情绪运动系统结构中未预期、预期和传递的厌恶直肠刺激的反应活性，这与胃肠道症状的减少有关。
Aim: To conduct a placebo-controlled functional brain imaging study to assess the effect of the 5-hydroxytryptamine-3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses.Methods: Fifty-two non-constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer-controlled barostat. Changes in regional cerebral blood flow were assessed using H (2) (15) O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales.Results: Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron.Conclusions: In non-constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.