Neurokinin-1-receptor antagonism decreases anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome: a pilot study.
Neurokinin-1-receptor antagonism decreases anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome: a pilot study.
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DOI：
10.1111/j.1365-2036.2011.04958.x
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发表时间：
2012-02
影响因子：
7.6
通讯作者：
Mayer E
中科院分区：
文献类型：
--
作者：
Tillisch K;Labus J;Nam B;Bueller J;Smith S;Suyenobu B;Siffert J;McKelvy J;Naliboff B;Mayer E
肠易激综合征的特征是慢性腹痛和频繁的共病焦虑。P物质/神经激肽-1受体系统参与疼痛和焦虑的调节，提示IBS的潜在治疗靶点。确定神经激肽-1受体（NK 1 R）的抑制是否会改变IBS女性患者的疼痛等级和大脑对实验性内脏疼痛和焦虑症状的反应。招募罗马II阳性IBS女性进行NK 1 R拮抗剂AV 608的双盲、安慰剂对照、交叉研究。治疗期为3周，洗脱期为2周。在第一次治疗前和治疗块后，在内脏扩张范例期间进行功能MRI。SPM 8被用来比较疼痛和非疼痛的内脏刺激与情绪唤醒和内感受相关的区域的大脑活动。负面影响，焦虑症状和疼痛评级进行了评估。11名受试者完成了研究，8名受试者提供了fMRI数据。与安慰剂相比，AV 608与焦虑、负面情绪和疼痛评分降低相关。在AV 608治疗期间，杏仁核、海马和前扣带回在内脏扩张期间显示出活动降低。AV 608还与与内感受相关的大脑区域（后扣带回、前扣带回中回）的活动减少有关。在IBS中用AV 608进行长期治疗与改善的情绪和疼痛评级以及情绪唤醒相关脑区域的活动相关。这表明，进一步探索NK 1 R拮抗剂是必要的内脏疼痛疾病，特别是在患者共病焦虑症状。
Irritable bowel syndrome is characterised by chronic abdominal pain and frequent comorbid anxiety. The substance P/neurokinin-1 receptor system is implicated in the regulation of both pain and anxiety, suggesting a potential therapeutic target in IBS. To determine whether inhibition of the neurokinin-1 receptor (NK1R) will change pain ratings and brain responses to experimental visceral pain and anxiety symptoms in women with IBS or not. Rome II positive IBS women were recruited for a double-blind, placebo-controlled, cross-over study of NK1R antagonist AV608. Treatment periods were 3 weeks with a 2-week washout period. Functional MRI during a visceral distension paradigm was performed before first treatment and after treatment blocks. SPM8 was used to compare brain activity during painful and nonpainful visceral stimuli in regions associated with emotional arousal and interoception. Negative affect, anxiety symptoms and pain ratings were assessed. Eleven subjects completed the study and eight subjects provided fMRI data. AV608, compared with placebo, was associated with reduced anxiety, negative affect, and pain ratings. During AV608 treatment, the amygdala, hippocampus and anterior cingulate gyrus showed decreased activity during visceral distension. AV608 was also associated with decreases in activity in brain regions associated with interoception (posterior insula, anterior mid-cingulate gyrus). Chronic treatment with AV608 in IBS is associated with improved mood and pain ratings and activity of emotional arousal related brain regions. This suggests that further exploration of NK1R antagonists is warranted in visceral pain disorders, particularly in patients with comorbid anxiety symptoms.
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