Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, South Australia 5042, Australia; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia 5000, Australia; Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, South Australia 5000, Australia.
Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, South Australia 5042, Australia; Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), North Terrace, Adelaide, South Australia 5000, Australia.
Trends Pharmacol Sci. 2022 Feb;43(2):110-122. doi: 10.1016/j.tips.2021.11.002. Epub 2021 Dec 2.
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects ~11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients. Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics.
肠易激综合征（IBS）是一种慢性胃肠道疾病，其特征为腹痛和排便习惯改变，影响全球约 11%的人口。在过去的十年中，临床前和临床研究揭示了多种与鸟苷酸环化酶-C（GC-C）激动剂内脏镇痛作用相关的新机制。在这里，我们讨论了 GC-C 激动剂靶向 GC-C/环鸟苷酸（cGMP）途径的机制，导致内脏镇痛以及 IBS 患者腹痛和其他感觉的临床相关缓解。由于证据占主导地位，我们重点介绍利那洛肽，一种 14 个氨基酸的 GC-C 激动剂，口服生物利用度非常低，在肠道内起作用。总的来说，实验和临床证据的权重支持 GC-C 激动剂作为外周作用内脏镇痛药的概念。
