Division of Neurogastroenterology/Motility, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Aliment Pharmacol Ther. 2020 Jun;51(12):1332-1341. doi: 10.1111/apt.15772. Epub 2020 May 13.
Linaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS-C) symptoms, but how it improves pain in humans is unknown.
To investigate the effects of linaclotide and placebo on the afferent and efferent gut-brain-gut signalling in IBS-C patients, in a randomised clinical trial.
Patients with IBS-C (Rome III) and rectal hypersensitivity were randomised (2:1) to receive linaclotide (290 µg) or placebo for 10 weeks and undergo bi-directional gut and brain axis assessment using anorectal electrical stimulations and transcranial/transspinal-anorectal magnetic stimulations. Rectal sensations were examined by balloon distention. Assessments included abdominal pain, bowel symptoms and quality of life (QOL) scores. Primary outcomes were latencies of recto-cortical and cortico-rectal evoked potentials.
Thirty-nine patients participated; 26 received linaclotide and 13 received placebo. Rectal cortical evoked potentials latencies (milliseconds) were significantly prolonged with linaclotide compared to baseline (P1:Δ 19 ± 6, P < 0.005; N1:Δ 20 ± 7, P < 0.02) but not with placebo (P1:Δ 3 ± 5; N1:Δ 4.7 ± 5,P = 0.3) or between groups. The efferent cortico-anorectal and spino-anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline (P < 0.001) and placebo (Δ 29 ± 10 vs 4 ± 20, (P < 0.03). Abdominal pain decreased (P < 0.001) with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased (P < 0.001), and IBS-QOL scores improved (P = 0.01) with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo (54% vs 23%, P = 0.13).
Linaclotide prolongs afferent gut-brain signalling from baseline but both afferent and efferent signalling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS-C symptoms and QOL compared to placebo. These mechanisms may explain the effects of linaclotide on pain relief in IBS-C patients. ClinicalTrials.Gov: Registered at Clinical trials.gov no NCT02078323.
利那洛肽是一种鸟苷酸环化酶 C 激动剂，可缓解以便秘为主的肠易激综合征（IBS-C）症状，但它如何改善人类的疼痛尚不清楚。
在一项随机临床试验中，研究利那洛肽和安慰剂对 IBS-C 患者内脏-大脑-内脏信号的影响。
采用直肠高敏性罗马 III 标准诊断为 IBS-C 的患者被随机（2:1）分为利那洛肽（290μg）或安慰剂组，接受为期 10 周的治疗，并使用直肠电刺激和经颅/经脊髓-直肠磁刺激进行双向内脏-大脑轴评估。通过球囊扩张检查直肠感觉。评估包括腹痛、肠道症状和生活质量（QOL）评分。主要结局为直肠-皮质和皮质-直肠诱发电位潜伏期。
共有 39 名患者参与，26 名患者接受利那洛肽治疗，13 名患者接受安慰剂治疗。与基线相比，利那洛肽治疗后直肠皮质诱发电位潜伏期（毫秒）显著延长（P1：Δ 19±6，P<0.005；N1：Δ 20±7，P<0.02），但安慰剂组无显著变化（P1：Δ 3±5；N1：Δ 4.7±5，P=0.3）或两组间无显著变化。皮质-直肠传出和脊髓-直肠传出潜伏期无变化。与基线相比，最大耐受直肠容量（cc）显著增加（P<0.001），与安慰剂相比也显著增加（Δ 29±10 比 4±20，P<0.03）。腹痛减轻（P<0.001），但组间无差异。利那洛肽组完全自发性排便频率增加（P<0.001），IBS-QOL 评分改善（P=0.01），与基线和安慰剂相比。利那洛肽组与安慰剂组的总应答者比例无差异（54%比 23%，P=0.13）。
与基线相比，利那洛肽延长了内脏-大脑的传入信号，但传入和传出信号均未受到安慰剂的影响。与安慰剂相比，利那洛肽显著改善直肠高敏性、IBS-C 症状和 QOL。这些机制可能解释了利那洛肽对 IBS-C 患者疼痛缓解的作用。ClinicalTrials.Gov：ClinicalTrials.gov 注册号为 NCT02078323。
Zotero 插件
