Pharmacotherapy for gastric and intestinal cramping pain: ‎ current and emerging therapies

References

• Zhu CP, Jiang F, Wang RQ, et al. Comparison of efficacy and safety of hyoscine butylbromide versus anisodamine for acute gastric or intestinal spasm-like pain: a randomized, double-blinded, multicenter phase III trial. J Dig Dis. 2017 Aug;18(8):453–460. doi: 10.1111/1751-2980.12504
   PubMed Web of Science ®Google Scholar
• Tytgat GN. Hyoscine butylbromide: a review of its use in treating abdominal cramping and pain. Drugs. 2007;67(9):1343–1357. doi: 10.2165/00003495-200767090-00007
   PubMed Web of Science ®Google Scholar
• Müller-Lissner S, Andresen V, Corsetti M, et al. Functional abdominal cramping pain: expert practical guidance. J Clin Gastroenterol. 2022 Nov 1;56(10):844–852. doi: 10.1097/MCG.0000000000001764
   PubMed Web of Science ®Google Scholar
• Drewes AM, Olesen AE, Farmer AD, et al. Gastrointestinal pain. Nat Rev Dis Primers. 2020 Jan 6;6(1):1. doi: 10.1038/s41572-019-0135-7
   PubMed Web of Science ®Google Scholar
• Farzaei MH, Bahramsoltani R, Abdollahi M, et al. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments. J Neurogastroenterol Motil. 2016;22(4):558. doi: 10.5056/jnm16001
   PubMed Web of Science ®Google Scholar
• Andrews ET, Beattie RM, Tighe MP. Functional abdominal pain: what clinicians need to know. Archives of disease in childhood. Arch Dischildhood. 2020 Oct;105(10):938–944. doi: 10.1136/archdischild-2020-318825
   PubMed Web of Science ®Google Scholar
• Makharia GK. Understanding and treating abdominal pain and spasms in organic gastrointestinal diseases: inflammatory bowel disease and biliary diseases. J Clin Gastroenterol. 2011 Aug;45:S89–93. doi: 10.1097/MCG.0b013e31821fbd82
   PubMed Web of Science ®Google Scholar
• Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s gastrointestinal and liver disease E-book: pathophysiology, diagnosis, management. Elsevier Health Sci. 2020;1:144–157 .
   Google Scholar
• Kleeff J, Whitcomb DC, Shimosegawa T, et al. Chronic pancreatitis. Nat Rev Dis Primers. 2017;3(1):1–18. doi: 10.1038/nrdp.2017.60
   Google Scholar
• Cartwright SL, Knudson MP. Evaluation of acute abdominal pain in adults. Am Fam Physician. 2008;77(7):971–9778.
   PubMed Web of Science ®Google Scholar
• Townsend CM, Beauchamp RD, Evers BM, et al. Sabiston textbook of surgery. Elsevier Health Sci. 2016. 1092–1119.
   Google Scholar
• Macaluso CR, McNamara RM. Evaluation and management of acute abdominal pain in the emergency department. Int J Gene Med. 2012;789–797. doi: 10.2147/IJGM.S25936
   PubMedGoogle Scholar
• Harrison TR, Jameson JL. Harrison’s principles of internal medicine| principles of internal medicine. United States of America: McGraw-Hill Education; 2018.
   Google Scholar
• Lukic S, Mijac D, Filipovic B, et al. Chronic abdominal pain: gastroenterologist approach. Dig Dis. 2022;40(2):181–186. doi: 10.1159/000516977
   PubMed Web of Science ®Google Scholar
• Norton C, Czuber-Dochan W, Artom M, et al. Systematic review: interventions for abdominal pain management in inflammatory bowel disease. Aliment Pharmacol Ther. 2017 Jul;46(2):115–125. doi: 10.1111/apt.14108
   PubMed Web of Science ®Google Scholar
• Pasricha PJ, Willis WD, Gebhart GF, et al. Chronic abdominal and visceral pain: theory and practice. CRC Press: 2006. doi: 10.3109/9781420004434
   Google Scholar
• Vermeulen W, De Man JG, Pelckmans PA, et al. Neuroanatomy of lower gastrointestinal pain disorders. World J Gastroenterol. 2014;20(4):1005. doi: 10.3748/wjg.v20.i4.1005
   PubMed Web of Science ®Google Scholar
• Spencer NJ, Hibberd TJ, Travis L, et al. Identification of a rhythmic firing pattern in the enteric nervous system that generates rhythmic electrical activity in smooth muscle. J Neurosci. 2018;38(24):5507–5522. doi: 10.1523/JNEUROSCI.3489-17.2018
   PubMed Web of Science ®Google Scholar
• Scholz J, Woolf CJ. Can we conquer pain? Nat Neurosci. 2002;5(Suppl 11):1062–1067. doi: 10.1038/nn942
   PubMedGoogle Scholar
• Anand P, Aziz Q, Willert R, et al. Peripheral and central mechanisms of visceral sensitization in man. Neurogastroenterol Motil. 2007;19(s1):29–46. doi: 10.1111/j.1365-2982.2006.00873.x
   PubMedGoogle Scholar
• Hazlett-Stevens H, Craske MG, Mayer EA, et al. Prevalence of irritable bowel syndrome among university students: the roles of worry, neuroticism, anxiety sensitivity and visceral anxiety. J Psychosom Res. 2003;55(6):501–505. doi: 10.1016/S0022-3999(03)00019-9
   PubMed Web of Science ®Google Scholar
• Drewes AM, Krarup AL, Detlefsen S, et al. Pain in chronic pancreatitis: the role of neuropathic pain mechanisms. Gut. 2008;57(11):1616–1627. doi: 10.1136/gut.2007.146621
   PubMed Web of Science ®Google Scholar
• Petersen P, Gao C, Arendt-Nielsen L, et al. Pain intensity and biomechanical responses during ramp-controlled distension of the human rectum. Digestive diseases and sciences. Dig Dis Sci. 2003;48(7):1310–1316. doi: 10.1023/A:1024107209436
   PubMed Web of Science ®Google Scholar
• Bueno L, De Ponti F, Fried M, et al. Serotonergic and non‐serotonergic targets in the pharmacotherapy of visceral hypersensitivity. Neurogastroenterol Motil. 2007;19(s1):89–119. doi: 10.1111/j.1365-2982.2006.00876.x
   PubMedGoogle Scholar
• De Schepper H, De Man J, Moreels T, et al. Gastrointestinal sensory and motor disturbances in inflammatory bowel disease–clinical relevance and pathophysiological mechanisms. Aliment Pharmacol Ther. 2008;27(8):621–637. doi: 10.1111/j.1365-2036.2008.03624.x
   PubMed Web of Science ®Google Scholar
• Dunlop S, Jenkins D, Neal K, et al. Randomized, double‐blind, placebo‐controlled trial of prednisolone in post‐infectious irritable bowel syndrome. Aliment Pharmacol Ther. 2003;18(1):77–84. doi: 10.1046/j.1365-2036.2003.01640.x
   PubMed Web of Science ®Google Scholar
• Wang H, Steeds J, Motomura Y, et al. CD4+ T cell-mediated immunological control of enterochromaffin cell hyperplasia and 5-hydroxytryptamine production in enteric infection. Gut. 2007;56(7):949–957. doi: 10.1136/gut.2006.103226
   PubMed Web of Science ®Google Scholar
• Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome 1. Gastroenterology. 2004;126(7):1657–1664. doi: 10.1053/j.gastro.2004.03.013
   PubMed Web of Science ®Google Scholar
• Camilleri M, Andrews CN, Bharucha AE, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology. 2007;132(1):17–25. doi: 10.1053/j.gastro.2006.11.020
   PubMed Web of Science ®Google Scholar
• Kumar S, Ranjan P, Mittal B, et al. Serotonin transporter gene (SLC6A4) polymorphism in patients with irritable bowel syndrome and healthy controls. J Gastrointestinal And Liver Dis. 2012;21(1):31–38.
   PubMed Web of Science ®Google Scholar
• Nilholm C, Roth B, Ohlsson B. A dietary intervention with reduction of starch and sucrose leads to reduced gastrointestinal and extra-intestinal symptoms in IBS patients. Nutrients. 2019;11(7):1662. doi: 10.3390/nu11071662
   PubMed Web of Science ®Google Scholar
• Farrugia A, Arasaradnam R. Bile acid diarrhoea: pathophysiology, diagnosis and management. Frontline Gastroenterol. 2021;12(6):500–507. doi: 10.1136/flgastro-2020-101436
   PubMed Web of Science ®Google Scholar
• Camilleri M, Boeckxstaens G. Irritable bowel syndrome: treatment based on pathophysiology and biomarkers. Gut. 2023;72(3):590–599. doi: 10.1136/gutjnl-2022-328515
   PubMed Web of Science ®Google Scholar
• Ishioh M, Nozu T, Okumura T. Brain neuropeptides, neuroinflammation, and irritable bowel syndrome. Digestion. 2023;6:1–6.
   Google Scholar
• Okumura T, Nozu T, Ishioh M, et al. Brain orexin improves intestinal barrier function via the vagal cholinergic pathway. Neurosci lett. 2020;714:134592. doi: 10.1016/j.neulet.2019.134592
   PubMed Web of Science ®Google Scholar
• Takahashi N, Okumura T, Yamada H, et al. Stimulation of gastric acid secretion by centrally administered orexin-A in conscious rats. Biochem Biophys Res Commun. 1999 Jan 27;254(3):623–627. doi: 10.1006/bbrc.1998.9994
   PubMed Web of Science ®Google Scholar
• Baccari MC. Orexins and gastrointestinal functions. Current Protein Pept Sci. 2010;11(2):148–155. doi: 10.2174/138920310790848377
   PubMed Web of Science ®Google Scholar
• Okumura T, Ishioh M, Nozu T. Central regulatory mechanisms of visceral sensation in response to colonic distension with special reference to brain orexin. Neuropeptides. 2021;86:102129. doi: 10.1016/j.npep.2021.102129
   PubMed Web of Science ®Google Scholar
• Yamada H, Takahashi N, Tanno S, et al. A selective orexin-1 receptor antagonist, SB334867, blocks 2-DG-induced gastric acid secretion in rats. Neurosci lett. 2005;376(2):137–142. doi: 10.1016/j.neulet.2004.11.043
   PubMed Web of Science ®Google Scholar
• Wu B, Liu Y, Liu F, et al. The antinociceptive effects and molecular mechanisms of ghrelin (1–7)-NH2 at the supraspinal level in acute pain in mice. Brain Res Bull. 2019;146:112–123. doi: 10.1016/j.brainresbull.2018.12.016
   PubMed Web of Science ®Google Scholar
• Mao Y, Li Z, Chen K, et al. Antinociceptive effect of ghrelin in a rat model of irritable bowel syndrome involves TRPV1/opioid systems. Cell Physiol Biochem. 2017 Sep 20;43(2):518–530. doi: 10.1159/000480478
   PubMedGoogle Scholar
• Samy W, El Gebaly A, Ahmed NH, et al. Ghrelin polymorphism/TRPV1 receptor expression in Egyptian IBS patients. Cytokine. 2022 Apr 1;152:155827. doi: 10.1016/j.cyto.2022.155827
   PubMed Web of Science ®Google Scholar
• Peeters TL. Central and peripheral mechanisms by which ghrelin regulates gut motility. J Physiol Pharmacol. 2003;54 Suppl 4(4):95–103.
   PubMedGoogle Scholar
• Sjölund K, Ekman R, Wierup N. Covariation of plasma ghrelin and motilin in irritable bowel syndrome. Peptides. 2010;31(6):1109–1112. doi: 10.1016/j.peptides.2010.03.021
   PubMed Web of Science ®Google Scholar
• El-Salhy M, Lillebø E, Reinemo A, et al. Ghrelin in patients with irritable bowel syndrome. Int J Mol Med. 2009;23(6):703–707. doi: 10.3892/ijmm_00000183
   PubMed Web of Science ®Google Scholar
• Şahin-Eryılmaz G, Başak K, Çakır-Madenci Ö, et al. Relationship between irritable bowel syndrome and plasma and tissue ghrelin levels. Turk J Gastroenterol. 2018;29(6):631. doi: 10.5152/tjg.2018.17593
   PubMed Web of Science ®Google Scholar
• Monem SM, Elbadrawy EG, Shalaby SM, et al. The role of serum gastric peptide ghrelin hormone level in irritable bowel syndrome at Zagazig University Hospitals. JMedLife. 2022;15(12):1525. doi: 10.25122/jml-2022-0089
   Google Scholar
• Okumura T, Nozu T, Ishioh M, et al. Oxytocin acts centrally in the brain to improve leaky gut through the vagus nerve and a cannabinoid signaling in rats. Physiol Behav. 2022;254:113914. doi: 10.1016/j.physbeh.2022.113914
   PubMed Web of Science ®Google Scholar
• Louvel D, Delvaux M, Felez A, et al. Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome. Gut. 1996;39(5):741–747. doi: 10.1136/gut.39.5.741
   PubMed Web of Science ®Google Scholar
• Welch MG, Margolis KG, Li Z, et al. Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice. Am J Physiol Gastrointest Liver Physiol. 2014;307(8):G848–62. doi: 10.1152/ajpgi.00176.2014
   PubMed Web of Science ®Google Scholar
• Li J, Liu H, Guo F, et al. Increased GABAergic projections in the paraventricular nucleus regulate colonic hypersensitivity via oxytocin in a rat model of irritable bowel syndrome. Neuroreport. 2022;34(2):108–115. doi: 10.1097/WNR.0000000000001867
   PubMed Web of Science ®Google Scholar
• Furgała A, Ciesielczyk K, Przybylska-Feluś M, et al. Postprandial effect of gastrointestinal hormones and gastric activity in patients with irritable bowel syndrome. Sci Rep. 2023;13(1):9420. doi: 10.1038/s41598-023-36445-1
   PubMed Web of Science ®Google Scholar
• Anderson S. Acute abdominal pain. Chapter 21, Acute Medicine. 2017. 138–143.
   PubMedGoogle Scholar
• Rahimi R, Nikfar S, Rezaie A, et al. Efficacy of tricyclic antidepressants in irritable bowel syndrome: a meta-analysis. World J Gastroenterol. 2009;15(13):1548. doi: 10.3748/wjg.15.1548
   PubMed Web of Science ®Google Scholar
• Keefer L, Drossman DA, Guthrie E, et al. Centrally mediated disorders of gastrointestinal pain. Gastroenterology. 2016 Feb 19;150(6):1408–1419. doi: 10.1053/j.gastro.2016.02.034
   Web of Science ®Google Scholar
• Keefer L, Ko CW, Ford AC. AGA clinical practice update on management of chronic gastrointestinal pain in disorders of gut-brain interaction: expert review. Clin Gastroenterol Hepatol. 2021 Dec;19(12):2481–2488.e1. doi: 10.1016/j.cgh.2021.07.006
   PubMed Web of Science ®Google Scholar
• Salari P, Abdollahi M. Systematic review of modulators of benzodiazepine receptors in irritable bowel syndrome: is there hope? World J Gastroenterol. 2011;17(38):4251. doi: 10.3748/wjg.v17.i38.4251
   PubMed Web of Science ®Google Scholar
• Mozaffari S, Rahimi R, Abdollahi M. Implications of melatonin therapy in irritable bowel syndrome: a systematic review. Curr Pharm Des. 2010;16(33):3646–3655. doi: 10.2174/138161210794079254
   PubMed Web of Science ®Google Scholar
• Rexwinkel R, de Bruijn CMA, Gordon M, et al. Pharmacologic treatment in functional abdominal pain disorders in children: a systematic review. Pediatrics. 2021 Jun;147(6). doi: 10.1542/peds.2020-042101
   PubMed Web of Science ®Google Scholar
• Korterink JJ, Rutten JM, Venmans L, et al. Pharmacologic treatment in pediatric functional abdominal pain disorders: a systematic review. J Paediatr. 2015 Feb;166(2):424–31.e6. doi: 10.1016/j.jpeds.2014.09.067
   PubMed Web of Science ®Google Scholar
• Corsetti M, Forestier S, Jiménez M. Hyoscine butylbromide mode of action on bowel motility: from pharmacology to clinical practice. Neurogastroenterol Motil. 2023;35(4):e14451. doi: 10.1111/nmo.14451
   PubMed Web of Science ®Google Scholar
• Tytgat GN. Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs. 2007;67(9):1343–1357. doi: 10.2165/00003495-200767090-00007
   PubMed Web of Science ®Google Scholar
• Poonai N, Kumar K, Coriolano K, et al. Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial. CMAJ. 2020;192(48):E1612–E1619. doi: 10.1503/cmaj.201055
   PubMed Web of Science ®Google Scholar
• Mousavi T, Nikfar S, Abdollahi M. An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome. Expert Opin Drug Metab Toxicol. 2020;16(7):583–604. doi: 10.1080/17425255.2020.1767067
   PubMed Web of Science ®Google Scholar
• Darvish-Damavandi M, Nikfar S, Abdollahi M. A systematic review of efficacy and tolerability of mebeverine in irritable bowel syndrome. World J Gastroenterol. 2010;16(5):547. doi: 10.3748/wjg.v16.i5.547
   PubMed Web of Science ®Google Scholar
• Daniluk J, Malecka-Wojciesko E, Skrzydlo-Radomanska B, et al. The efficacy of mebeverine in the treatment of irritable bowel syndrome—A systematic review. J Clin Med. 2022;11(4):1044. doi: 10.3390/jcm11041044
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Efficacy and safety of mebeverine + simethicone in patients with functional bowel disorders Maryland, United States: ClinicalTrials.gov; 2022 [cited 2023 Mar 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT05175131
   Google Scholar
• Martínez-Vázquez MA, Vázquez-Elizondo G, González-González JA, et al. Effect of antispasmodic agents, alone or in combination, in the treatment of irritable bowel syndrome: systematic review and meta-analysis. Revista de gastroenterologia de Mexico. 2012 Apr;77(2):82–90. doi: 10.1016/j.rgmx.2012.04.002
   PubMedGoogle Scholar
• Bor S, Lehert P, Chalbaud A, et al. Efficacy of pinaverium bromide in the treatment of irritable bowel syndrome: a systematic review and meta-analysis. Therap Adv Gastroenterol. 2021;14:17562848211033740. doi: 10.1177/17562848211033740
   Web of Science ®Google Scholar
• Lee KN, Lee OY, Choi MG, et al. Efficacy and safety of tiropramide in the treatment of patients with irritable bowel syndrome: a multicenter, randomized, double-blind, non-inferiority trial compared with octylonium. J Neurogastroenterol Motil. 2014 Jan;20(1):113–121. doi: 10.5056/jnm.2014.20.1.113
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Comparative efficacy and safety of fenoverine (FEN-401)MD. United States: ClinicalTrials.gov; 2012 [cited 2023 Mar 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT01507922
   Google Scholar
• Rahman MZ, Ahmed DS, Mahmuduzzaman M, et al. Comparative efficacy and safety of trimebutine versus mebeverine in the treatment of irritable bowel syndrome. Mymensingh Med J. 2014 Jan;23(1):105–113.
   PubMedGoogle Scholar
• Rai RR, Nijhawan S. Comparative evaluation of efficacy and safety of drotaverine versus mebeverine in irritable bowel syndrome: a randomized double-blind controlled study. Saudi J Gastroenterol. 2021 May;27(3):136–143. doi: 10.4103/sjg.SJG_266_20
   PubMed Web of Science ®Google Scholar
• ClinicalTrials gov. Efficacy and safety of Meteospasmyl® in irritable bowel syndrome Maryland, United States: ClinicalTrials gov; 2007 [cited 2023 Mar 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT00542295
   Google Scholar
• Wittmann T, Paradowski L, Ducrotté P, et al. Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome–a randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2010 Mar;31(6):615–624. doi: 10.1111/j.1365-2036.2009.04216.x
   PubMed Web of Science ®Google Scholar
• Barraza-Ortiz DA, Pérez-López N, Medina-López VM, et al. Combination of a Probiotic and an antispasmodic increases quality of life and reduces symptoms in patients with irritable bowel syndrome: a pilot study. Dig Dis. 2021;39(3):294–300. doi: 10.1159/000510950
   PubMed Web of Science ®Google Scholar
• Callan NW, Johnson DL, Westcott MP, et al. Herb and oil composition of dill (Anethum graveolens L.): effects of crop maturity and plant density. Ind Crops Prod. 2007;25(3):282–287. doi: 10.1016/j.indcrop.2006.12.007
   Web of Science ®Google Scholar
• Nagai H, Yamamoto Y, Sato Y, et al. Pharmaceutical evaluation of cultivated Glycyrrhiza uralensis roots in comparison of their antispasmodic activity and glycycoumarin contents with those of licorice. Biol Pharm Bull. 2006;29(12):2442–2445. doi: 10.1248/bpb.29.2442
   PubMed Web of Science ®Google Scholar
• Emendörfer F, Emendörfer F, Bellato F, et al. Antispasmodic activity of fractions and cynaropicrin from Cynara scolymus on guinea-pig ileum. Biol Pharm Bull. 2005;28(5):902–904. doi: 10.1248/bpb.28.902
   PubMed Web of Science ®Google Scholar
• Natividad GM, Broadley KJ, Kariuki B, et al. Actions of Artemisia vulgaris extracts and isolated sesquiterpene lactones against receptors mediating contraction of guinea pig ileum and trachea. J Ethnopharmacol. 2011;137(1):808–816. doi: 10.1016/j.jep.2011.06.042
   PubMed Web of Science ®Google Scholar
• Begrow F, Engelbertz J, Feistel B, et al. Impact of thymol in thyme extracts on their antispasmodic action and ciliary clearance. Planta Med. 2009;76:311–318. doi: 10.1055/s-0029-1186179
   PubMed Web of Science ®Google Scholar
• Hazelhoff B, Malingré TM, Meijer D. Antispasmodic effects of valeriana compounds: an in-vivo and in-vitro study on the guinea-pig ileum. Arch Int Pharmacodyn Ther. 1982;257(2):274–287.
   PubMedGoogle Scholar
• Mengistu M, Abebe Y, Mekonnen Y, et al. In vivo and in vitro hypotensive effect of aqueous extract of Moringa stenopetala. Afr Health Sci. 2012;12(4):545–551. doi: 10.4314/ahs.v12i4.23
   PubMed Web of Science ®Google Scholar
• Gilani AH, Shah AJ, Zubair A, et al. Chemical composition and mechanisms underlying the spasmolytic and bronchodilatory properties of the essential oil of Nepeta cataria L. J Ethnopharmacol. 2009;121(3):405–411. doi: 10.1016/j.jep.2008.11.004
   PubMed Web of Science ®Google Scholar
• Pavlović I, Krunić A, Nikolić D, et al. Chloroform extract of underground parts of Ferula heuffelii: secondary metabolites and spasmolytic activity. Chemistry & Biodiversity. 2014;11(9):1417–1427. doi: 10.1002/cbdv.201400094
   PubMed Web of Science ®Google Scholar
• Sadraei H, Shokoohinia Y, Sajjadi S, et al. Antispasmodic effects of Prangos ferulacea acetone extract and its main component osthole on ileum contraction. Res Pharm Sci. 2013;8(2):137.
   PubMedGoogle Scholar
• Maschi O, Cero ED, Galli GV, et al. Inhibition of human cAMP-phosphodiesterase as a mechanism of the spasmolytic effect of Matricaria recutita L. J Agric Food Chemistry. 2008;56(13):5015–5020. doi: 10.1021/jf800051n
   PubMed Web of Science ®Google Scholar
• Abu-Niaaj L, Abu-Zarga M, Sabri S, et al. Isolation and biological effects of 7-O-methyleriodictyol, a flavanone isolated from Artemisia monosperma, on rat isolated smooth muscles. Planta Med. 1993;59(1):42–45. doi: 10.1055/s-2006-959601
   PubMed Web of Science ®Google Scholar
• Alexandrovich I, Rakovitskaya O, Kolmo E, et al. The effect of fennel (foeniculum vulgare) seed oil emulsion in infantile colic: a randomized, placebo-controlled study. Altern Ther Health Med. 2003;9(4):58.
   PubMed Web of Science ®Google Scholar
• Seifi A, Changizi S, Khori V, et al. Hydro-alcoholic extract of Matricaria recutita exhibited dual anti-spasmodic effect via modulation of Ca2+ channels, NO and PKA2-kinase pathway in rabbit jejunum. Avicenna J Phytomed. 2017;7(4):334.
   PubMedGoogle Scholar
• González-Cortazar M, Tortoriello J, Alvarez L. Norsecofriedelanes as spasmolytics, advances of structure-activity relationships. Planta Med. 2005;71(8):711–716. doi: 10.1055/s-2005-871224
   PubMed Web of Science ®Google Scholar
• Riyazi A, Hensel A, Bauer K, et al. The effect of the volatile oil from ginger rhizomes (Zingiber officinale), its fractions and isolated compounds on the 5-HT3 receptor complex and the serotoninergic system of the rat ileum. Planta Med. 2007;73(4):355–362. doi: 10.1055/s-2007-967171
   PubMed Web of Science ®Google Scholar
• Cometa MF, Parisi L, Palmery M, et al. In vitro relaxant and spasmolytic effects of constituents from Viburnum prunifolium and HPLC quantification of the bioactive isolated iridoids. J Ethnopharmacol. 2009;123(2):201–207. doi: 10.1016/j.jep.2009.03.021
   PubMed Web of Science ®Google Scholar
• Khan A-U, Gilani A-H, Najeeb-Ur-Rehman. Pharmacological studies on Hypericum perforatum fractions and constituents. Pharm Biol. 2011;49(1):46–56. doi: 10.3109/13880209.2010.494307
   PubMed Web of Science ®Google Scholar
• Ahluwalia B, Magnusson MK, Böhn L, et al. Randomized clinical trial: effects of aloe barbadensis mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2020;32(8):e13860. doi: 10.1111/nmo.13860
   PubMed Web of Science ®Google Scholar
• Riva A, Giacomelli L, Togni S, et al. Oral administration of a lecithin-based delivery form of boswellic acids (Casperome®) for the prevention of symptoms of irritable bowel syndrome: a randomized clinical study. Minerva Gastroenterol Dietol. 2019;65(1):30–35. doi: 10.23736/S1121-421X.18.02530-8
   PubMed Web of Science ®Google Scholar
• Y-B W, Y-K D, Zhang L, et al. Pharmacological treatments of Chinese herbal medicine for irritable bowel syndrome in adults: a network meta-analysis of randomized controlled trials. PLoS One. 2021;16(8):e0255665. doi: 10.1371/journal.pone.0255665
   PubMed Web of Science ®Google Scholar
• Chen Z, Nie Z, Sun Q. Clinical study in treating intractable ulcerative colitis with traditional Chinese medicine. Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi Jiehe Zazhi=. Chin J Integr Med Traditional And Western Medicine. 1994;14(7):400–402.
   Google Scholar
• Lopresti AL, Smith SJ, Rea A, et al. Efficacy of a curcumin extract (Curcugen™) on gastrointestinal symptoms and intestinal microbiota in adults with self-reported digestive complaints: a randomised, double-blind, placebo-controlled study. BMC Complement Med Ther. 2021;21(1):1–17. doi: 10.1186/s12906-021-03220-6
   PubMedGoogle Scholar
• Hanai H, Iida T, Takeuchi K, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol. 2006;4(12):1502–1506. doi: 10.1016/j.cgh.2006.08.008
   PubMed Web of Science ®Google Scholar
• Agah S, Taleb AM, Moeini R, et al. Chamomile efficacy in patients of the irritable bowel syndrome. Der Pharma Chemica. 2015 Jan 01;7:41–45.
   Google Scholar
• Nee J, Ballou S, Kelley JM, et al. Peppermint oil treatment for irritable bowel syndrome: a randomized placebo-controlled trial. Am J Gastroenterol. 2021;116(11):2279–2285. doi: 10.14309/ajg.0000000000001395
   PubMed Web of Science ®Google Scholar
• Weerts ZZR, Masclee AA, Witteman BJ, et al. Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Gastroenterology. 2020;158(1):123–136. doi: 10.1053/j.gastro.2019.08.026
   PubMed Web of Science ®Google Scholar
• Cash B, Epstein M. Patient satisfaction with IBS symptom relief using a novel peppermint oil delivery system in a randomized clinical trial and in the General population. Int J Dig Dis. 2016 Jan 02;2.doi: 10.4172/2472-1891.100027
   Google Scholar
• Ingrosso MR, Ianiro G, Nee J, et al. Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome. Aliment Pharmacol Ther. 2022;56(6):932–941. doi: 10.1111/apt.17179
   PubMed Web of Science ®Google Scholar
• Gong Y, Zha Q, Li L, et al. Efficacy and safety of fufangkushen colon-coated capsule in the treatment of ulcerative colitis compared with mesalazine: a double-blinded and randomized study. J Ethnopharmacol. 2012;141(2):592–598. doi: 10.1016/j.jep.2011.08.057
   PubMed Web of Science ®Google Scholar
• Hawrelak JA, Myers SP. Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study. J Altern Complementary Med. 2010;16(10):1065–1071. doi: 10.1089/acm.2009.0090
   PubMed Web of Science ®Google Scholar
• Janczura M, Kobus-Moryson M, Sip S, et al. Fixed-dose combination of NSAIDs and spasmolytic agents in the treatment of different types of pain—A practical review. J Clin Med. 2021 Jul 15;10(14):3118. doi: 10.3390/jcm10143118
   PubMed Web of Science ®Google Scholar
• Mueller‐Lissner S, Tytgat G, Paulo L, et al. Placebo‐and paracetamol‐controlled study on the efficacy and tolerability of hyoscine butylbromide in the treatment of patients with recurrent crampy abdominal pain. Aliment Pharmacol Ther. 2006;23(12):1741–1748. doi: 10.1111/j.1365-2036.2006.02818.x
   PubMed Web of Science ®Google Scholar
• Sanchez Martinez J, Goiz Durán I. Clinical assessment of the tolerability and the effect of IK-19 in tablet form on pain of spastic origin. Invest Med Int. 1988;15:63–65.
   Google Scholar
• Schäfer E, Ewe K. The treatment of irritable colon. Efficacy and tolerance of buscopan plus, buscopan, paracetamol and placebo in ambulatory patients with irritable colon. Fortschr Med. 1990 Aug 30;108(25):488–492.
   PubMedGoogle Scholar
• Remington-Hobbs J, Petts G, Harris T. Emergency department management of undifferentiated abdominal pain with hyoscine butylbromide and paracetamol: a randomised control trial. Emer Med J. 2012;29(12):989–994. doi: 10.1136/emermed-2011-200474
   PubMed Web of Science ®Google Scholar
• Mousavi T, Nikfar S, Abdollahi M. An update on the use of pharmacotherapy for opioid-induced bowel dysfunction. Expert Opin Pharmacother. 2023 Feb 11;24(3):359–375.
   PubMed Web of Science ®Google Scholar
• Ranjbar S, Seyednejad SA, Nikfar S, et al. How can we develop better antispasmodics for irritable bowel syndrome? Expert Opin Drug Discov. 2019;14(6):549–562. doi: 10.1080/17460441.2019.1593369
   PubMed Web of Science ®Google Scholar
• Törnblom H, Drossman DA. Psychotropics, antidepressants, and visceral analgesics in functional gastrointestinal disorders. Curr Gastroenterol Rep. 2018;20:1–10. doi: 10.1007/s11894-018-0664-3
   PubMedGoogle Scholar
• Andresen V, Montori VM, Keller J, et al. Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Gastroenterol Hepatol. 2008;6(5):545–555. doi: 10.1016/j.cgh.2007.12.015
   PubMed Web of Science ®Google Scholar
• Rahimi R, Nikfar S, Abdollahi M. Efficacy and tolerability of alosetron for the treatment of irritable bowel syndrome in women and men: a meta-analysis of eight randomized, placebo-controlled, 12-week trials. Clin Ther. 2008;30(5):884–901. doi: 10.1016/j.clinthera.2008.05.002
   PubMed Web of Science ®Google Scholar
• Lacy BE, Nicandro JP, Chuang E, et al. Alosetron use in clinical practice: significant improvement in irritable bowel syndrome symptoms evaluated using the US Food and drug administration composite endpoint. Therap Adv Gastroenterol. 2018;11:1756284818771674. doi: 10.1177/1756284818771674
   Web of Science ®Google Scholar
• Fukudo S, Kinoshita Y, Okumura T, et al. Ramosetron reduces symptoms of irritable bowel syndrome with diarrhea and improves quality of life in women. Gastroenterology. 2016;150(2):358–366. e8. doi: 10.1053/j.gastro.2015.10.047
   PubMed Web of Science ®Google Scholar
• Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea. Gut. 2014;63(10):1617–1625. doi: 10.1136/gutjnl-2013-305989
   PubMed Web of Science ®Google Scholar
• Ohno Y. Therapeutic role of 5‐HT1A receptors in the treatment of schizophrenia and Parkinson’s disease. CNS Neurosci Ther. 2011;17(1):58–65. doi: 10.1111/j.1755-5949.2010.00211.x
   PubMed Web of Science ®Google Scholar
• Tack J, Janssen P, Masaoka T, et al. Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia. Clin Gastroenterol Hepatol. 2012;10(11):1239–1245. doi: 10.1016/j.cgh.2012.06.036
   PubMed Web of Science ®Google Scholar
• Karim MA, Al-Baz N, Haddad PM, et al. Buspirone in the management of refractory irritable bowel syndrome: a case report. Medicine. 2021;100(51):e28003. doi: 10.1097/MD.0000000000028003
   PubMed Web of Science ®Google Scholar
• Lan L, Chen Y-L, Zhang H, et al. Efficacy of tandospirone in patients with irritable bowel syndrome-diarrhea and anxiety. World J Gastroenterol. 2014;20(32):11422. doi: 10.3748/wjg.v20.i32.11422
   PubMed Web of Science ®Google Scholar
• Tack J, Van Den Elzen B, Tytgat G, et al. A placebo-controlled trial of the 5-HT1A agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia. Neurogastroenterol Motil. 2009;21(6):619-26, e23–4. doi: 10.1111/j.1365-2982.2008.01260.x
   Web of Science ®Google Scholar
• Calandre EP, Rico-Villademoros F, Galán J, et al. Quetiapine extended-release (seroquel-XR) versus amitriptyline monotherapy for treating patients with fibromyalgia: a 16-week, randomized, flexible-dose, open-label trial. Psychopharmacology. 2014;231(12):2525–2531. doi: 10.1007/s00213-013-3422-0
   PubMed Web of Science ®Google Scholar
• McIntyre A, Paisley D, Kouassi E, et al. Quetiapine fumarate extended‐release for the treatment of major depression with comorbid fibromyalgia syndrome: a double‐blind, randomized, placebo‐controlled study. Arthritis & Rheumat. 2014;66(2):451–461. doi: 10.1002/art.38228
   PubMed Web of Science ®Google Scholar
• Grover M, Dorn SD, Weinland SR, et al. Atypical antipsychotic quetiapine in the management of severe refractory functional gastrointestinal disorders. Dig Dis Sci. 2009;54(6):1284–1291. doi: 10.1007/s10620-009-0723-6
   PubMed Web of Science ®Google Scholar
• Navari RM. Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting. Eur J Pharmacol. 2014;722:180–186. doi: 10.1016/j.ejphar.2013.08.048
   PubMed Web of Science ®Google Scholar
• Waldman SA, Camilleri M. Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders. Gut. 2018;67(8):1543–1552. doi: 10.1136/gutjnl-2018-316029
   PubMed Web of Science ®Google Scholar
• Johnston JM, Kurtz CB, MacDougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology. 2010;139(6):1877–1886. e2. doi: 10.1053/j.gastro.2010.08.041
   PubMed Web of Science ®Google Scholar
• Rao S, Lembo AJ, Shiff SJ, et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. Am J Gastroenterol. 2012;107(11):1714. doi: 10.1038/ajg.2012.255
   PubMed Web of Science ®Google Scholar
• Miner PB Jr., Koltun WD, Wiener GJ, et al. A randomized phase III clinical trial of plecanatide, a Uroguanylin Analog, in patients with chronic idiopathic constipation. Am J Gastroenterol. 2017 Apr;112(4):613–621. doi: 10.1038/ajg.2016.611
   PubMed Web of Science ®Google Scholar
• Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety Off. J Am Col Gastroenterol. 2012;107(11):1702–1712. doi: 10.1038/ajg.2012.254
   PubMed Web of Science ®Google Scholar
• Smart D, Sabido‐David C, Brough SJ, et al. SB‐334867‐A: the first selective orexin‐1 receptor antagonist. Br J Pharmacol. 2001;132(6):1179–1182. doi: 10.1038/sj.bjp.0703953
   PubMed Web of Science ®Google Scholar
• Funayama T, Nozu T, Ishioh M, et al. Centrally administered GLP-1 analogue improves intestinal barrier function through the brain orexin and the vagal pathway in rats. Brain Res. 2023;1809:148371. doi: 10.1016/j.brainres.2023.148371
   PubMed Web of Science ®Google Scholar
• Ishioh M, Nozu T, Igarashi S, et al. Ghrelin acts in the brain to block colonic hyperpermeability in response to lipopolysaccharide through the vagus nerve. Neuropharmacology. 2020 Aug 15;173:108116. doi: 10.1016/j.neuropharm.2020.108116
   PubMed Web of Science ®Google Scholar
• Mosińska P, Zatorski H, Storr M, et al. Future treatment of constipation-associated disorders: role of relamorelin and other ghrelin receptor agonists. J Neurogastroenterol Motil. 2017;23(2):171. doi: 10.5056/jnm16183
   PubMed Web of Science ®Google Scholar
• Camilleri M, Acosta A. Emerging treatments in neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist. Neurogastroenterol Motil. 2015;27(3):324–332. doi: 10.1111/nmo.12490
   PubMed Web of Science ®Google Scholar
• Borg J, Ohlsson B. Oxytocin prolongs the gastric emptying time in patients with diabetes mellitus and gastroparesis, but does not affect satiety or volume intake in patients with functional dyspepsia. BMC Res Notes. 2012;5(1):1–8. doi: 10.1186/1756-0500-5-148
   PubMedGoogle Scholar
• De Araujo AD, Mobli M, Castro J, et al. Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain. Nat Commun. 2014;5(1):3165. doi: 10.1038/ncomms4165
   PubMedGoogle Scholar
• Xu S, Qin B, Shi A, et al. Oxytocin inhibited stress induced visceral hypersensitivity, enteric glial cells activation, and release of proinflammatory cytokines in maternal separated rats. Eur J Pharmacol. 2018;818:578–584. doi: 10.1016/j.ejphar.2017.11.018
   PubMed Web of Science ®Google Scholar
• Ray K. Oxytocin analogues have potential in relieving chronic abdominal pain. Nat Rev Gastroenterol Hepatol. 2014;11(4):202–. doi: 10.1038/nrgastro.2014.20
   PubMedGoogle Scholar
• Black CJ, Ford AC. Global burden of irritable bowel syndrome: trends, predictions and risk factors. Nat Rev Gastroenterol Hepatol. 2020;17(8):473–486. doi: 10.1038/s41575-020-0286-8
   PubMed Web of Science ®Google Scholar