Opioid misuse in gastroenterology and non-opioid management of abdominal pain

Szigethy, Eva; Knisely, Mitchell; Drossman, Douglas

doi:10.1038/nrgastro.2017.141

Cited by 118Opioid Use Disorder TreatmentPain Management and Opioid UseAnesthesia and Pain Management

Opioid misuse in gastroenterology and non-opioid management of abdominal pain

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Szigethy, Eva, Knisely, Mitchell, Drossman, Douglas·2018·Nature Reviews Gastroenterology & Hepatology

DOI 10.1038/nrgastro.2017.141PMC PMC6421506

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Abstract

Opioids were one of the earliest classes of medications used for pain across a variety of conditions, but morbidity and mortality have been increasingly associated with their chronic use. Despite these negative consequences, chronic opioid use is increasing worldwide, with the USA and Canada having the highest rates. Chronic opioid use for noncancer pain can have particularly negative effects in the gastrointestinal and central nervous systems, including opioid-induced constipation, narcotic bowel syndrome, worsening psychopathology and addiction. This Review summarizes the evidence of opioid misuse in gastroenterology, including the lack of evidence of a benefit from these drugs, as well as the risk of harm and negative consequences of opioid use relative to the brain-gut axis. Guidelines for opioid management and alternative pharmacological and nonpharmacological strategies for pain management in patients with gastrointestinal disorders are also discussed. As chronic pain is complex and involves emotional and social factors, a multimodal approach targeting both pain intensity and quality of life is best.

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Narcotic bowel syndrome is an opioid-induced paradoxical hyperalgesia.
“the development of narcotic bowel syndrome, an opioid induced paradoxical hyperalgesia. 26”
From Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome (2021) · cites this paper as [26]
Opioids are linked to compounding and deleterious gastrointestinal-related adverse effects, collectively known as opioid-induced bowel dysfunction.
“This would fit with ample evidence linking opioids to compounding and deleterious gastrointestinalrelated adverse effects, collectively known as opioid -induced bowel dysfunction. 26”
From Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome (2021) · cites this paper as [26]
Among the most common symptoms of opioid-induced bowel dysfunction are abdominal pain, nausea, reflux, vomiting, and constipation.
“Among the most common symptoms of opioid-induced bowel dysfunction are abdominal pain, nausea, reflux, vomiting, and constipation”
From Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome (2021) · cites this paper as [26]

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Palonosetron and hydroxyzine pre-treatment reduces the objective signs of experimentally-induced acute opioid withdrawal in humans: a double-blinded, randomized, placebo-controlled crossover study
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Patients With Short Bowel on Narcotics During 2 Randomized Trials Have Abdominal Complaints Independent of Teduglutide
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[126]Saito YA A placebo-controlled trial of pregabalin for irritable bowel syndrome. Am. J. Gastroenterol. Suppl 111, S236 (2016).
[134]Lacy BE, Chey WD & Lembo AJ New and emerging treatment options for Irritable Bowel Syndrome. Gastroenterol. Hepatol 11 (Suppl. 2), 1– 19 (2015). PMC4612133 26491416

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Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut−Brain Interaction): A Rome Foundation Working Team Report
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Bharucha, A. E., Kudva, Y. C., & Prichard, D. O. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00161 · Cited by 252 · see citing works
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“epidemiological data suggest that quality of life or functional capacity are not improved [75,81,82].”
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Vitamin D and Its Potential Interplay With Pain Signaling Pathways
Habib, A. M., Nagi, K., Thillaiappan, N. B., Sukumaran, V., & Akhtar, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00820 · Cited by 120 · see citing works
“At present, no other oral therapeutic drug provides instant and effective relief of severe pain (151, 152).”
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International consensus guidelines on interventional endoscopy in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club
Kitano, M., Gress, T. M., Garg, P. K., Itoi, T., Irisawa, A., Isayama, H., Kanno, A., Takase, K., Levy, M. L., Yasuda, I., et al. (2020) · Pancreatology · doi:10.1016/j.pan.2020.05.022 · Cited by 106 · see citing works
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İçer, M. A., Sarıkaya, B., Koçyiğit, E., Atabılen, B., Çelik, M. N., Capasso, R., Ağagündüz, D., & Budán, F. (2024) · Foods · doi:10.3390/foods13152437 · Cited by 102 · see citing works
Advances in Management of Esophageal Motility Disorders
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Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity
Cruz-Lebrón, A., Johnson, R., Mazahery, C., Troyer, Z., Joussef-Piña, S., Quiñones‐Mateu, M. E., Strauch, C., Hazen, S. L., & Levine, A. D. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1946368 · Cited by 73 · see citing works
“Participants in these programs, and most opioid users, experience a vast array of symptoms including gastrointestinal motility disorders(7,34,35) due to OIBD, a debilitating side of effect of chronic opioid use.(4,6,34,35) This study focused on the impact of chronic methadone use on the gut microbiome, the consequent…”
Background
Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome
Lam, C. Y., Palsson, O. S., Whitehead, W. E., Sperber, A. D., Tornblom, H., Simren, M., & Aziz, I. (2021) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.02.034 · Cited by 71 · see citing works
Oxidative Metabolism as a Modulator of Kratom’s Biological Actions
Chakraborty, S., Uprety, R., Slocum, S. T., Irie, T., Rouzic, V. L., Li, X., Wilson, L., Scouller, B., Alder, A. F., Kruegel, A. C., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01111 · Cited by 61 · see citing works
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Management of Opioid-Induced Constipation and Bowel Dysfunction: Expert Opinion of an Italian Multidisciplinary Panel
GIORGIO, R. D., Zucco, F., Chiarioni, G., Mercadante, S., Corazziari, E. S., Caraceni, A. T., Odetti, P. R., Giusti, R., Marinangeli, F., & Pinto, C. (2021) · Advances in Therapy · doi:10.1007/s12325-021-01766-y · Cited by 56 · see citing works
Problematic Use of Prescription Opioids and Medicinal Cannabis Among Patients Suffering from Chronic Pain
Feingold, D., Goor‐Aryeh, I., Brill, S., Delayahu, Y., & Lev‐Ran, S. (2016) · Pain Medicine · doi:10.1093/pm/pnw134 · Cited by 44 · see citing works
The burden of Chronic Pelvic Pain (CPP): Costs and quality of life of women and men with CPP treated in outpatient referral centers
Hutton, D. W., Mustafa, A., Patil, S., Rathod, S., Shrikhande, G., Advincula, A. P., Drummond, J., Gregersen, P. K., Hall, J. F., Metz, C. N., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0269828 · Cited by 38 · see citing works
“This is not only a burden on healthcare utilization, but a significant disservice to CPP patients who are made worse by opioids [36, 37] and are looking for diagnostic expertise and a treatment plan.”
Background
Diabetic gastroparesis: current challenges and future prospects
Avalos, D. J., Sarosiek, I., Loganathan, P., & McCallum, R. W. (2018) · Clinical and Experimental Gastroenterology · doi:10.2147/ceg.s131650 · Cited by 38 · see citing works
“124 In addition, opioids can further delay GE in patients with GP and lead to worsening symptoms.”
Opioid analgesia: recent developments
Stein, C. (2020) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000495 · Cited by 38 · see citing works
“Meta-analyses show clinically insignificant reduction of pain scores, and epidemiological data suggest that quality of life or functional capacity are not improved [10,28,30].”
Background
Spinal DN-9, a Peptidic Multifunctional Opioid/Neuropeptide FF Agonist Produced Potent Nontolerance Forming Analgesia With Limited Side Effects
Wang, Z., Xu, B., Jiang, C., Zhang, T., Zhang, M., Li, N., Zhang, Q., Xu, K., Chen, D., Xiao, J., et al. (2019) · Journal of Pain · doi:10.1016/j.jpain.2019.08.016 · Cited by 35 · see citing works
Chronic abdominal pain and persistent opioid use after bariatric surgery
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“Adjuvant analgesics may be relevant as supplement and have a specific role in the presence of central sensitization or major psychological components [36].”
Background
Developing a better biopsychosocial understanding of pain in inflammatory bowel disease: a cross-sectional study
Sweeney, L., Moss-Morris, R. E., Czuber‐Dochan, W., Murrells, T., & Norton, C. S. (2019) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000001615 · Cited by 31 · see citing works
Pain in Inflammatory Bowel Disease Is Not Improved During Hospitalization: The Impact of Opioids on Pain and Healthcare Utilization
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“Over the past 10 years, hospitalizations for IBD have increased [10] and the majority of hospitalized patients with IBD are prescribed narcotics during hospitalization [11, 12].”
Background
Gastric Emptying Scans: Poor Adherence to National Guidelines
Wise, J. L., Vázquez‐Roque, M. I., McKinney, C. J., Zickella, M., Crowell, M. D., & Lacy, B. E. (2020) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06314-2 · Cited by 31 · see citing works
The Prevalence, Comorbidity, Management and Costs of Irritable Bowel Syndrome: An Observational Study Using Routine Health Insurance Data
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“IBS symptoms such as abdominal pain and constipation (narcotic bowel syndrome) (25).”
Background
Systematic Review: Psychosocial Correlates of Pain in Pediatric Inflammatory Bowel Disease
Murphy, L. K., de la Vega, R., Kohut, S. A., Kawamura, J., Levy, R. L., & Palermo, T. M. (2020) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izaa115 · Cited by 27 · see citing works
Chronic continuous abdominal pain: evaluation of diagnostic features, iatrogenesis and drug treatments in a cohort of 103 patients
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Review article: A practical approach to persistent gastrointestinal symptoms in inflammatory bowel disease in remission
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“102 Pelvic floor dysfunction can also aggravate symptoms in these patients.”
Background
Pain Characteristics in Patients with Inflammatory Bowel Disease: A Monocentric Cross-Sectional Study
Hardy, P., Fikri, J., Libbrecht, D., Louis, E. J., & Joris, J. L. (2022) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjac051 · Cited by 25 · see citing works
Metabolic Profiles Associated with Opioid Use and Opioid Use Disorder: a Narrative Review of the Literature
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Managing Pain and Psychosocial Care in IBD: a Primer for the Practicing Gastroenterologist
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Cleave, J. H. V., Booker, S. Q., Powell-Roach, K. L., Liang, E., & Kawi, J. (2021) · Pain Management Nursing · doi:10.1016/j.pmn.2020.11.007 · Cited by 23 · see citing works
Update S3-Leitlinie Intestinale Motilitätsstörungen: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM)
Keller, J., Wedel, T., Seidl, H., Kreis, M. E., van der Voort, I., Gebhard, M., Langhorst, J., Jansen, P. L., Schwandner, O., Storr, M., et al. (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1646-1279 · Cited by 22 · see citing works
“[123] Szigethy E, Knisely M, Drossman D.”
Impact of Opioid Consumption in Patients With Functional Gastrointestinal Disorders
Melchior, C., Desprez, C., Wuestenberghs, F., Leroi, A., Lemaire, A., & Goucerol, G. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.596467 · Cited by 21 · see citing works
“Considering their gastrointestinal (GI) side effects, and the lack of efficacy to relieve pain in functional GI disorders (FGID), opioids are not recommended in the treatment of painful FGID (Szigethy et al., 2018).”
Background
Increasing Rates of Opioid Prescriptions for Gastrointestinal Diseases in the United States
LeBrett, W. G., Chen, F. W., Yang, L., & Chang, L. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001052 · Cited by 20 · see citing works
Pain management in chronic pancreatitis incorporating safe opioid practices: Challenge accepted
Shah, I., Sheth, S. G., & Kothari, D. J. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i23.3142 · Cited by 19 · see citing works
Implications of the Opioid Epidemic for the Clinical Gastroenterology Practice
Thapa, N., Kappus, M. R., Hurt, R. T., & Diamond, S. J. (2019) · Current Gastroenterology Reports · doi:10.1007/s11894-019-0712-7 · Cited by 18 · see citing works
Pain Management in Patients With Inflammatory Bowel Disease.
Szigethy, E. (2018) · PubMed Central · Cited by 17 · see citing works
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Psychopharmacologic Therapies for Irritable Bowel Syndrome
Törnblom, H., & Drossman, D. A. (2021) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2021.04.005 · Cited by 17 · see citing works
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Pain therapy – Are there new options on the horizon?
Stein, C., & Köpf, A. (2019) · Best Practice & Research Clinical Rheumatology · doi:10.1016/j.berh.2019.06.002 · Cited by 16 · see citing works
In vitro and in vivo Pharmacological Activities of 14-O-Phenylpropyloxymorphone, a Potent Mixed Mu/Delta/Kappa-Opioid Receptor Agonist With Reduced Constipation in Mice
Lattanzi, R., Rief, S., Schmidhammer, H., Negri, L., & Spetea, M. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01002 · Cited by 15 · see citing works
Evaluation of Opioid Use in Acute Pancreatitis in Absence of Chronic Pancreatitis: Absence of Opioid Dependence an Important Feature
Ahmed, A., Yakah, W., Freedman, S. D., Kothari, D. J., & Sheth, S. G. (2020) · The American Journal of Medicine · doi:10.1016/j.amjmed.2020.03.010 · Cited by 14 · see citing works
Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study
Brenner, D. M., Argoff, C. E., Fox, S. M., Bochenek, W. J., D'Astoli, P., Blakesley, R. E., Reasner, D. S., O'Dea, C. R., & Cash, B. D. (2020) · Pain · doi:10.1097/j.pain.0000000000001754 · Cited by 14 · see citing works
“acetylcholine, which prevents water and electrolyte movement into the GI tract, resulting in slower intestinal transit.(8,36) Opioid-”
Background
Neuromodulators in the Brain-Gut Axis: their Role in the Therapy of the Irritable Bowel Syndrome
Stănculete, M. F., Dumitrascu, D. L., & Drossman, D. A. (2021) · Journal of Gastrointestinal and Liver Diseases · doi:10.15403/jgld-4090 · Cited by 14 · see citing works
Self-citation
Oxytocin Analogues for the Oral Treatment of Abdominal Pain
Kremsmayr, T., Schober, G., Kaltenböck, M., Hoare, B. L., Brierley, S. M., & Muttenthaler, M. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202415333 · Cited by 13 · see citing works
Cognitive Behavioral Therapy for Insomnia: A Promising Treatment for Insomnia, Pain, and Depression in Patients With IBD
Salwen‐Deremer, J. K., Siegel, C. A., & Smith, M. T. (2020) · Crohn s & Colitis 360 · doi:10.1093/crocol/otaa052 · Cited by 15 · see citing works
Although tapentadol and oxycodone both increase colonic volume, tapentadol treatment resulted in softer stools and less constipation: a mechanistic study in healthy volunteers
Mark, E. B., Frøkjær, J. B., Hansen, T. M., Nedergaard, R. B., & Drewes, A. M. (2021) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2020-0151 · Cited by 13 · see citing works
AGA Institute Quality Indicator Development for Irritable Bowel Syndrome
Hung, K. W., Leiman, D. A., Kaza, A., Watson, R. R., Chang, L., & Maratt, J. K. (2025) · Gastroenterology · doi:10.1053/j.gastro.2024.11.003 · Cited by 12 · see citing works
Recent Advances in the Management of Severe Gastrointestinal Dysmotility
Vasant, D. H., & Lal, S. (2021) · Clinical and Experimental Gastroenterology · doi:10.2147/ceg.s249877 · Cited by 12 · see citing works
“53,73 Therefore, access to a specialist pain management team to assist with weaning from opioids and implement more appropriate, alternative pain management strategies is extremely beneficial within the multidisciplinary team.”
Background
Ambulatory assessment of colonic motility using the electromagnetic capsule tracking system: Effect of opioids
Mark, E. B., Klinge, M. W., Grønlund, D., Poulsen, J. L., Schlageter, V., Scott, S. M., Krogh, K., & Drewes, A. M. (2019) · Neurogastroenterology & Motility · doi:10.1111/nmo.13753 · Cited by 12 · see citing works
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Safaei, F., Shahrokh, S., Naderi, N., Rastegar, R., & Shamsi, A. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1468885 · Cited by 2 · see citing works
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Authors: Szigethy, E., Knisely, M., & Drossman, D.
Affiliations: University of Pittsburgh (US)
University of North Carolina at Chapel Hill (US)
Corresponding author: Szigethy, Eva
ORCID: Szigethy, Eva
Knisely, Mitchell
Drossman, Douglas
Venue: Nature Reviews Gastroenterology & Hepatology
Publisher: Springer Science and Business Media LLC
Published: 2017-11-15
Volume: 15
Issue: 3
Pages: 168-180
ISSN: 1759-5045 (ISSN-L)
1759-5053
DOI: 10.1038/nrgastro.2017.141
PMC: PMC6421506
OpenAlex: W2768878405
Cited by: 117
References: 202
Citations by year: 2026: 6 · 2025: 8 · 2024: 10 · 2023: 14 · 2022: 15 · 2021: 23 · 2020: 17 · 2019: 15 · 2018: 7 · 2017: 1 · 2016: 1
FWCI: 1.78
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Reviews Gastroenterology & Hepatology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: American Psychiatric Publishing
American Academy of Child and Adolescent Psychiatry
Shionogi
National Institutes of Health
National Institute of Nursing Research (T32NR009759)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Health Sciences › Medicine › Surgery › Anesthesia and Pain Management
Keywords: opioid misuse, chronic opioid use, abdominal pain, gastrointestinal diseases, opioid-induced constipation, narcotic bowel syndrome, opioid use disorder, gut-brain axis, non-pharmacological pain management, multimodal pain management, chronic non-cancer pain
MeSH terms: Analgesics, Analgesics, Opioid, Gastroenterology, Humans, Abdominal Pain, Inappropriate Prescribing, Pain Management

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Opioid misuse in gastroenterology and non-opioid management of abdominal pain

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