https://doi.org/10.4081/ahr.2024.2

Emerging potential therapies for chronic abdominal visceral pain: an overview

Vol. 1 (2024)
Published: March 18, 2024
Chronic abdominal pain, cannabinoid, Salbutamol, MOR, 5-HT4 receptors, pomegranate mesocarp, guanylate cyclase-C agonists, vegetal molecules, CGRP, palmitoylethanolamide
Abstract Views: 3285
PDF: 322
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Martina Rekatsina
mrekatsina@gmail.com
https://orcid.org/0000-0002-7671-4056
Professor of Anesthesia and Pain Management, University of Athens, Greece.
Giustino Varrassi
https://orcid.org/0000-0002-3822-2923
Paolo Procacci Foundation, Rome, Italy.

Despite advancements in pain medicine, management of chronic abdominal visceral discomfort remains a substantial concern for both patients and physicians. Standard pharmacological treatment fails to produce meaningful therapeutic outcomes. As a result, researchers are working on identifying additional modulable targets. Among others, specific receptors (serotonin, α2 adrenergic, cholecystokinin), as well as transient receptor potential vanilloid-1 channel, calcitonin gene-related peptide, mitogen-activated protein kinase and hypothalamic-pituitary-adrenal axis have been proposed as specific targets. Identification of genetic polymorphisms also plays a significant role. In this narrative review, which follows the SANRA criteria, we aimed to present the latest developments of the past five years, in visceral analgesia, without focusing on established pain management modalities. Cannabinoid receptor 2 agonists, high-dose inhaled salbutamol, μ-opioid receptors agonist in acidified microenvironment, 5-HT 4 receptor-antagonist, pomegranate mesocarp, guanylate cyclase-C agonists, assembled system of molecules of vegetal origin, monoclonal antibodies against calcitonin gene-related peptide receptors, palmitoylethanolamide, as well as polydatin micro-RNA based treatments have a possible role in the management of abdominal visceral pain. However, more research is needed because the majority of the findings are based on animal models of visceral pain or preliminary human investigations.

Altmetrics

Downloads

Download data is not yet available.
Perrot S, Cohen M, Barke A, et al. The IASP classification of chronic pain for ICD-11: chronic secondary musculoskeletal pain. Pain 2019;160:77-82. DOI: https://doi.org/10.1097/j.pain.0000000000001389
Lakhoo K, Almario CV, Khalil C, Spiegel BMR. Prevalence and characteristics of abdominal pain in the United States. Clin Gastroenterol Hepatol 2021;19:1864-72.e5. DOI: https://doi.org/10.1016/j.cgh.2020.06.065
Camilleri M, Boeckxstaens G. Dietary and pharmacological treatment of abdominal pain in IBS. Gut 2017;66:966-74. DOI: https://doi.org/10.1136/gutjnl-2016-313425
Varrassi G, Coaccioli S, De-Andrés J, et al. Expert consensus on clinical use of an orally administered dexketoprofen plus tramadol fixed-dose combination in moderate-to-severe acute pain: A Delphi study. Adv Ther 2019;36:3174-85. DOI: https://doi.org/10.1007/s12325-019-01096-0
Drewes AM, Bouwense SAW, Campbell CM, et al. Guidelines for the understanding and management of pain in chronic pancreatitis. Pancreatology 2017;17:720-31. DOI: https://doi.org/10.1016/j.pan.2017.07.006
Urits I, Jones MR, Orhurhu V, et al. A comprehensive review of the celiac plexus block for the management of chronic abdominal pain. Curr Pain Headache Rep 2020;24:42. DOI: https://doi.org/10.1007/s11916-020-00878-4
Kapural L, Lee N, Badhey H, et al. Splanchnic block at T11 provides a longer relief than celiac plexus block from nonmalignant, chronic abdominal pain. Pain Manag 2019;9:115-21. DOI: https://doi.org/10.2217/pmt-2018-0056
Al-Jumah R, Urits I, Viswanath O, et al. Radiofrequency ablation and alcohol neurolysis of the splanchnic nerves for a patient with abdominal pain from pancreatic cancer. Cureus 2020;12:e10758. DOI: https://doi.org/10.7759/cureus.10758
Labanski A, Langhorst J, Engler H, Elsenbruch S. Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge. Psychoneuroendocrinology 2020;111:104501. DOI: https://doi.org/10.1016/j.psyneuen.2019.104501
Baethge C, Goldbeck-Wood S, Mertens S. SANRA-a scale for the quality assessment of narrative review articles. Res Integr Peer Rev 2019;4:5. DOI: https://doi.org/10.1186/s41073-019-0064-8
Urits I, Li N, Bahrun E, et al. An evidence-based review of CGRP mechanisms in the propagation of chronic visceral pain. Best Pract Res Clin Anaesthesiol 2020;34:507-16. DOI: https://doi.org/10.1016/j.bpa.2020.06.007
Sadeghi M, Erickson A, Castro J, et al. Contribution of membrane receptor signalling to chronic visceral pain. Int J Biochem Cell Biol 2018;98:10-23. DOI: https://doi.org/10.1016/j.biocel.2018.02.017
Brumovsky PR, Gebhart GF. Visceral organ cross-sensitization - an integrated perspective. Auton Neurosci 2010;153:106-15. DOI: https://doi.org/10.1016/j.autneu.2009.07.006
Radovanovic-Dinic B, Tesic-Rajkovic S, Grgov S, et al. Irritable bowel syndrome - from etiopathogenesis to therapy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2018;162:1-9. DOI: https://doi.org/10.5507/bp.2017.057
Rekatsina M, Paladini A, Piroli A, et al. Pathophysiologic approach to pain therapy for complex pain entities: a narrative review. Pain Ther 2020;9:7-21. DOI: https://doi.org/10.1007/s40122-019-00147-2
Chen Y, Zhao Y, Wang L, et al. Involvement of Pirt /TRPV1 signalling in acupuncture-induced reduction of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome rats. Zhen Ci Yan Jiu 2021;46:278-83.
Yagihashi M, Kano M, Muratsubaki T, et al. Concordant pattern of the HPA axis response to visceral stimulation and CRH administration. Neurosci Res 2021;168:32-40. DOI: https://doi.org/10.1016/j.neures.2021.03.004
Huang Y, Zhang D, Li ZY, et al. Moxibustion Eases chronic inflammatory visceral pain in rats via MAPK signalling pathway in the spinal cord. J Pain Res 2019;12:2999-3012. DOI: https://doi.org/10.2147/JPR.S218588
Mehta H. Abdominal pain. In: David S, editor. Clinical pathways in emergency medicine. New Delhi: Springer; 2016. p. 329-45. DOI: https://doi.org/10.1007/978-81-322-2710-6_26
Kim HJ, Kim HJ. Centrally mediated abdominal pain syndrome. Korean J Gastroenterol 2021;77:277-84. DOI: https://doi.org/10.4166/kjg.2021.405
Azmy DJ, Qualia CM. Review of abdominal migraine in children. Gastroenterol Hepatol (N Y) 2020;16):632-9.
Nicholas M, Vlaeyen JWS, Rief W, et al. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain 2019;160:28-37. DOI: https://doi.org/10.1097/j.pain.0000000000001390
Drossman DA, Hasler WL. Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology 2016;150:1257-61. DOI: https://doi.org/10.1053/j.gastro.2016.03.035
Zhang L, Kline RH 4th, McNearney TA, et al. Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis. Mol Pain 2014;10:66. DOI: https://doi.org/10.1186/1744-8069-10-66
Castro J, Garcia-Caraballo S, Maddern J, et al. Olorinab (APD371), a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, reduces colitis-induced acute and chronic visceral hypersensitivity in rodents. Pain 2022;163:e72-e86 DOI: https://doi.org/10.1097/j.pain.0000000000002314
Yacyshyn BR, Hanauer S, Klassen P, et al. Safety, pharmacokinetics, and efficacy of olorinab, a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, in a phase 2a study of patients with chronic abdominal pain associated with Crohn's disease. Crohns Colitis 360 2020;3:otaa089. DOI: https://doi.org/10.1093/crocol/otaa089
Chang L, Cash BD, Lembo A, et al. Efficacy and safety of olorinab, a full agonist of the cannabinoid receptor 2, for the treatment of abdominal pain in patients with irritable bowel syndrome: Results from a phase 2b randomized placebo-controlled trial (CAPTIVATE). Neurogastroenterol Motil 2023;35:e14539. DOI: https://doi.org/10.1111/nmo.14539
Frugier C, Graham F, Samaan K, et al. Potential efficacy of high-dose inhaled salbutamol for the treatment of abdominal pain during oral food challenge. J Allergy Clin Immunol Pract 2021;9:3130-7. DOI: https://doi.org/10.1016/j.jaip.2021.03.040
Jiménez-Vargas NN, Yu Y, Jensen DD, et al. Agonist that activates the µ-opioid receptor in acidified microenvironments inhibits colitis pain without side effects. Gut 2022;71:695-704. DOI: https://doi.org/10.1136/gutjnl-2021-324070
Lyubashina OA, Sivachenko IB. The 5-HT4 receptor-mediated inhibition of visceral nociceptive neurons in the rat caudal ventrolateral medulla. Neuroscience 2017;359:277-88. DOI: https://doi.org/10.1016/j.neuroscience.2017.07.039
Parisio C, Lucarini E, Micheli L, et al. Pomegranate mesocarp against colitis-induced visceral pain in rats: effects of a decoction and its fractions. Int J Mol Sci 2020;21:4304. DOI: https://doi.org/10.3390/ijms21124304
Alkhatib M, Fayad C, Badran A, et al. Preventive and therapeutic effects of Punica granatum (pomegranate) in respiratory and digestive diseases: a review. Appl Sci 2022;12:12326. DOI: https://doi.org/10.3390/app122312326
Boulete IM, Thadi A, Beaufrand C, et al. Oral treatment with plecanatide or dolcanatide attenuates visceral hypersensitivity via activation of guanylate cyclase-C in rat models. World J Gastroenterol 2018;24:1888-900. DOI: https://doi.org/10.3748/wjg.v24.i17.1888
Shailubhai K, Palejwala V, Arjunan KP, et al. Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis. World J Gastrointest Pharmacol Ther 2015;6:213-22. DOI: https://doi.org/10.4292/wjgpt.v6.i4.213
Brierley SM, Grundy L, Castro J, et al. Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain. Trends Pharmacol Sci 2022;43:110-22. DOI: https://doi.org/10.1016/j.tips.2021.11.002
Yiannakou Y, Agrawal A, Allen PB, et al. UK clinical experience up to 52 weeks with linaclotide for irritable bowel syndrome with constipation. Therap Adv Gastroenterol 2018;11:1756284818798791. DOI: https://doi.org/10.1177/1756284818798791
Liu L, Zhang W, Zhao W, et al. Linaclotide for treating patients with irritable bowel syndrome with predominant constipation: a multicentre study of real-world data in China. Therap Adv Gastroenterol 2022;15:17562848221092596. DOI: https://doi.org/10.1177/17562848221092596
Parisio C, Lucarini E, Micheli L, et al. Researching new therapeutic approaches for abdominal visceral pain treatment: preclinical effects of an assembled system of molecules of vegetal origin. Nutrients 2019;12:22. DOI: https://doi.org/10.3390/nu12010022
Del Giorno R, Skaper S, Paladini A, et al. Palmitoylethanolamide in fibromyalgia: results from prospective and retrospective observational studies. Pain Ther 2015;4:169-78. DOI: https://doi.org/10.1007/s40122-015-0038-6
Paladini A, Fusco M, Cenacchi T, et al. Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis. Pain Physician 2016;19:11-24. DOI: https://doi.org/10.36076/ppj/2016.19.11
Paladini A, Varrassi G, Bentivegna G, et al. Palmitoylethanolamide in the treatment of failed back surgery syndrome. Pain Res Treat 2017;2017:1486010. DOI: https://doi.org/10.1155/2017/1486010
Cremon C, Stanghellini V, Barbaro MR, et al. Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome. Aliment Pharmacol Ther 2017;45:909-22. DOI: https://doi.org/10.1111/apt.13958
Varrassi G, Paladini A, Corno C, et al. A decades-long journey of palmitoylethanolamide (PEA), as a cornerstone in chronic neuropathic pain management: a comprehensive narrative review. Preprints 2024;2024030174. DOI: https://doi.org/10.20944/preprints202403.0174.v1
Camilleri M. What's in the pipeline for lower functional gastrointestinal disorders in the next 5 years? Am J Physiol Gastrointest Liver Physiol 2019;317:G640-50. DOI: https://doi.org/10.1152/ajpgi.00205.2019
Zhou Q, Yang L, Larson S, et al. Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1. Gut 2016;65:797-805. DOI: https://doi.org/10.1136/gutjnl-2013-306464
Sun J, Liang W, Yang X, et al. Cytoprotective effects of galacto-oligosaccharides on colon epithelial cells via up-regulating miR-19b. Life Sci 2019;231:116589. DOI: https://doi.org/10.1016/j.lfs.2019.116589
Hou Q, Huang Y, Zhang C, et al. MicroRNA-200a targets cannabinoid receptor 1 and serotonin transporter to increase visceral hyperalgesia in diarrhea-predominant irritable bowel syndrome rats. J Neurogastroenterol Motil 2018;24:656-68. DOI: https://doi.org/10.5056/jnm18037
Zhu H, Xiao X, Chai Y, et al. MiRNA-29a modulates visceral hyperalgesia in irritable bowel syndrome by targeting HTR7. Biochem Biophys Res Commun 2019;511:671-8. DOI: https://doi.org/10.1016/j.bbrc.2019.02.126
Ji NN, Meng QX, Wang Y, et al. Microglia-derived TNF-α inhibiting GABAergic neurons in the anterior lateral bed nucleus of the stria terminalis precipitates visceral hypersensitivity induced by colorectal distension in rats. Neurobiol Stress 2022;18:100449. DOI: https://doi.org/10.1016/j.ynstr.2022.100449
Dumitrascuta M, Martin C, Ballet S, Spetea M. Bifunctional peptidomimetic G protein-biased mu-opioid receptor agonist and neuropeptide FF receptor antagonist KGFF09 shows efficacy in visceral pain without rewarding effects after subcutaneous administration in mice. Molecules 2022;27:8785. DOI: https://doi.org/10.3390/molecules27248785
Jiang Y, Castro J, Blomster LV, et al. Pharmacological inhibition of the voltage-gated sodium channel NaV1.7 alleviates chronic visceral pain in a rodent model of irritable bowel syndrome. ACS Pharmacol Transl Sci 2021;4:1362-78. DOI: https://doi.org/10.1021/acsptsci.1c00072
Maatoug R, Jebali J, Guieu R, et al. BotAF, a new Buthus occitanus tunetanus scorpion toxin, produces potent analgesia in rodents. Toxicon 2018;149:72-85. DOI: https://doi.org/10.1016/j.toxicon.2018.01.003
Ford AC, Vanner S, Kashyap PC, Nasser Y. Chronic visceral pain: new peripheral mechanistic insights and resulting treatments. Gastroenterology 2024:S0016-5085(24)00132-X. Online Ahead of Print.

How to Cite

1.
Rekatsina M, Varrassi G. Emerging potential therapies for chronic abdominal visceral pain: an overview. Adv Health Res [Internet]. 2024 Mar. 18 [cited 2025 Feb. 23];1(1). Available from: https://www.ahr-journal.org/site/article/view/2
Copyright (c) 2024 the Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.