Main idea: Linaclotide prolongs afferent gut-brain signaling from baseline but both afferent and efferent signaling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS-C symptoms, and QOL compared to placebo.
Linaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS-C) symptoms. However, the pain-relieving properties are still unknown. The aims were to investigate the effects of linaclotide and placebo on the afferent and efferent gut-brain-gut signaling in IBS-C patients, in a randomized clinical trial. Patients with IBS-C and rectal hypersensitivity were randomized (2:1) to receive linaclotide (290 µg) or placebo for 10 weeks. 39 patients participated; 26 received linaclotide and 13 received placebos. 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 different cortico-anorectal and spino-anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline and placebo. Abdominal pain decreased with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased, and IBS-QOL scores improved with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo.