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  • Review Article
  • Published:

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

Key Points

  • Prescription opioid use is a global epidemic, with substantial increases in opioid-related morbidity and mortality around the world

  • There is a lack of evidence supporting the use of opioids for the management of chronic abdominal pain

  • Opioid use can have deleterious consequences on the gastrointestinal tract, including opioid-induced constipation and narcotic bowel syndrome

  • Many promising non-opioid pharmacological and nonpharmacological alternatives for treating abdominal pain exist; however, additional research is needed to identify best practices for treating abdominal pain in individuals with gastrointestinal disorders

  • If opioids are prescribed, it is essential to have strategies to monitor and manage opioid misuse, continually monitor risk–benefit clinical profiles, and prevent and treat addiction

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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Figure 1: Trends in total opioid consumption by country between 1994 and 2014.
Figure 2: Summary of opioid-induced effects within the gastrointestinal system.
Figure 3: Putative mechanisms for narcotic bowel syndrome and other models of opioid-induced hyperalgesia.

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References

  1. Berterame, S. et al. Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. Lancet 387, 1644–1656 (2016).

    PubMed  Google Scholar 

  2. University of Wisconsin–Madison Pain & Policy Studies Group. Opioid consumption data. Pain & Policy Studies Group http://www.painpolicy.wisc.edu/opioid-consumption-data (2017).

  3. Denisco, R. A., Chandler, R. K. & Compton, W. M. Addressing the intersecting problems of opioid misuse and chronic pain treatment. Exp. Clin. Psychopharmacol. 16, 417–428 (2008).

    PubMed  PubMed Central  Google Scholar 

  4. Zin, C. S., Chen, L. C. & Knaggs, R. D. Changes in trends and pattern of strong opioid prescribing in primary care. Eur. J. Pain 18, 1343–1351 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Ruscitto, A., Smith, B. H. & Guthrie, B. Changes in opioid and other analgesic use 1995-2010: repeated cross-sectional analysis of dispensed prescribing for a large geographical population in Scotland. Eur. J. Pain 19, 59–66 (2015).

    CAS  PubMed  Google Scholar 

  6. Weisberg, D. F., Becker, W. C., Fiellin, D. A. & Stannard, C. Prescription opioid misuse in the United States and the United Kingdom: cautionary lessons. Int. J. Drug Policy 25, 1124–1130 (2014).

    PubMed  Google Scholar 

  7. The Economist. The problem of pain. The Economist http://www.economist.com/news/international/21699363-americans-are-increasingly-addicted-opioids-meanwhile-people-poor-countries-die (2016).

  8. Berry, P. H. & Dahl, J. L. The new JCAHO pain standards: implications for pain management nurses. Pain Manag. Nurs. 1, 3–12 (2000).

    CAS  PubMed  Google Scholar 

  9. World Health Organization. WHO's cancer pain ladder for adults. World Health Organization http://www.who.int/cancer/palliative/painladder/en/ (2016).

  10. Manubay, J., Muchow, C. & Sullivan, M. Prescription drug abuse: epidemiology, regulatory issues, chronic pain management with narcotic analgesics. Prim. Care 38, 71–90 (2011).

    PubMed  PubMed Central  Google Scholar 

  11. Chang, H. Y., Daubresse, M., Kruszewski, S. P. & Alexander, G. C. Prevalence and treatment of pain in EDs in the United States, 2000 to 2010. Am. J. Emerg. Med. 32, 421–431 (2014).

    PubMed  Google Scholar 

  12. Daubresse, M. et al. Ambulatory diagnosis and treatment of nonmalignant pain in the United States, 2000–2010. Med. Care 51, 870–878 (2013).

    PubMed  Google Scholar 

  13. Rudd, R. A., Aleshire, N., Zibbell, J. E. & Gladden, R. M. Increases in drug and opioid overdose deaths — United States, 2000–2014. MMWR Morb. Mortal. Wkly Rep. 64, 1378–1382 (2016).

    PubMed  Google Scholar 

  14. Department of Health and Human Services, USA. The opioid epidemic: by the numbers. HHS.gov http://www.hhs.gov/sites/default/files/Factsheet-opioids-061516.pdf (2016).

  15. National Institute on Drug Abuse. Overdose death rates. National Institute on Drug Abuse https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates (2015).

  16. Inocencio, T. J., Carroll, N. V., Read, E. J. & Holdford, D. A. The economic burden of opioid-related poisoning in the United States. Pain Med. 14, 1534–1547 (2013).

    PubMed  Google Scholar 

  17. Ronan, M. V. & Herzig, S. J. Hospitalizations related to opioid abuse/dependence and associated serious infections increased sharply, 2002–2012. Health Aff. 35, 832–837 (2016).

    Google Scholar 

  18. Vowles, K. E. et al. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain 156, 569–576 (2015).

    PubMed  Google Scholar 

  19. Tuteja, A. K., Biskupiak, J., Stoddard, G. J. & Lipman, A. G. Opioid-induced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol. Motil. 22, 424–e96 (2010).

    CAS  PubMed  Google Scholar 

  20. Substance Abuse and Mental Health Services Administration (SAMHSA). National estimates of drug-related emergency department visits, 2004–2011. Substance Abuse and Mental Health Services Administration (SAMHSA) http://www.samhsa.gov/data/emergency-department-data-dawn/reports (2014).

  21. Blanch, B., Pearson, S. A. & Haber, P. S. An overview of the patterns of prescription opioid use, costs and related harms in Australia. Br. J. Clin. Pharmacol. 78, 1159–1166 (2014).

    PubMed  PubMed Central  Google Scholar 

  22. Degenhardt, L. et al. The global epidemiology and burden of opioid dependence: results from the global burden of disease 2010 study. Addiction 109, 1320–1333 (2014).

    PubMed  Google Scholar 

  23. Marienfeld, C. Heroin addiction, methadone, and HIV in China. Lancet Psychiatry 3, 799–800 (2016).

    PubMed  Google Scholar 

  24. Boscarino, J. A. et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system. Addiction 105, 1776–1782 (2010).

    PubMed  Google Scholar 

  25. Fleming, M. F., Balousek, S. L., Klessig, C. L., Mundt, M. P. & Brown, D. D. Substance use disorders in a primary care sample receiving daily opioid therapy. J. Pain 8, 573–582 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Katz, N. P. et al. Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesth. Analg. 97, 1097–1102 (2003).

    CAS  PubMed  Google Scholar 

  27. Passik, S. D., Kirsh, K. L., Donaghy, K. B. & Portenoy, R. K. Pain and aberrant drug-related behaviors in medically ill patients with and without histories of substance abuse. Clin. J. Pain 22, 173–181 (2006).

    PubMed  Google Scholar 

  28. Feingold, D., Goor-Aryeh, I., Bril, S., Delayahu, Y. & Lev-Ran, S. Problematic use of prescription opioids and medicinal cannabis among patients suffering from chronic pain. Pain Med. 18, 294–306 (2016).

    Google Scholar 

  29. Hughes, P. A., Costello, S. P., Bryant, R. V. & Andrews, J. M. Opioidergic effects on enteric and sensory nerves in the lower GI tract; basic mechanisms and clinical implications. Am. J. Physiol. Gastrointest. Liver Physiol. 311, G501–G513 (2016).

    PubMed  Google Scholar 

  30. Levy, B., Paulozzi, L., Mack, K. A. & Jones, C. M. Trends in opioid analgesic-prescribing rates by specialty, U. S., 2007–2012. Am. J. Prev. Med. 49, 409–413 (2015).

    PubMed  PubMed Central  Google Scholar 

  31. IMS Institute for Healthcare Informatics. Medicines used and spending in the U. S.: A review of 2015 and outlook to 2020 (IMS Institute for Healthcare Informatics, 2016).

  32. Bharucha, A. E., Chakraborty, S. & Sletten, C. D. Common functional gastroenterological disorders associated with abdominal pain. Mayo Clin. Proc. 91, 1118–1132 (2016).

    PubMed  PubMed Central  Google Scholar 

  33. Buckley, J. P., Kappelman, M. D., Allen, J. K., Van Meter, S. A. & Cook, S. F. The burden of comedication among patients with inflammatory bowel disease. Inflamm. Bowel Dis. 19, 2725–2736 (2013).

    PubMed  Google Scholar 

  34. Buckley, J. P., Cook, S. F., Allen, J. K. & Kappelman, M. D. Prevalence of chronic narcotic use among children with inflammatory bowel disease. Clin. Gastroenterol. Hepatol. 13, 310–315.e2 (2015).

    PubMed  Google Scholar 

  35. Cross, R. K., Wilson, K. T. & Binion, D. G. Narcotic use in patients with Crohn's disease. Am. J. Gastroenterol. 100, 2225–2229 (2005).

    PubMed  Google Scholar 

  36. Lichtenstein, G. R. et al. Serious infection and mortality in patients with Crohn's disease: more than 5 years of follow-up in the TREAT registry. Am. J. Gastroenterol. 107, 1409–1422 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Long, M. D., Barnes, E. L., Herfarth, H. H. & Drossman, D. A. Narcotic use for inflammatory bowel disease and risk factors during hospitalization. Inflamm. Bowel Dis. 18, 869–876 (2012).

    PubMed  Google Scholar 

  38. Nusrat, S., Yadav, D. & Bielefeldt, K. Pain and opioid use in chronic pancreatitis. Pancreas 41, 264–270 (2012).

    CAS  PubMed  Google Scholar 

  39. Dorn, S. et al. Patients with IBS commonly use narcotics [abstract]. Gastroenterology 138 (Suppl. 1), W1378 (2010).

    Google Scholar 

  40. Barth, K. S. et al. Screening for current opioid misuse and associated risk factors among patients with chronic nonalcoholic pancreatitis pain. Pain Med. 15, 1359–1364 (2014).

    PubMed  PubMed Central  Google Scholar 

  41. Olesen, S. S., Poulsen, J. L., Broberg, M. C., Madzak, A. & Drewes, A. M. Opioid treatment and hypoalbuminemia are associated with increased hospitalisation rates in chronic pancreatitis outpatients. Pancreatology 16, 807–813 (2016).

    CAS  PubMed  Google Scholar 

  42. Morley, K. I., Ferris, J. A., Winstock, A. R. & Lynskey, M. T. Polysubstance use and misuse or abuse of prescription opioid analgesics: a multi-level analysis of international data. Pain 158, 1138–1144 (2017).

    CAS  PubMed  Google Scholar 

  43. Sharma, A. & Jamal, M. M. Opioid induced bowel disease: a twenty-first century physicians' dilemma. Considering pathophysiology and treatment strategies. Curr. Gastroenterol. Rep. 15, 334 (2013).

    PubMed  Google Scholar 

  44. American Pain Society & American Academy of Pain Medicine. Guideline for the use of chronic opioid therapy in chronic noncancer pain: evidence review (American Pain Society, 2009).

  45. Wilder-Smith, C. H., Hill, L., Osler, W. & O'Keefe, S. Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis. Dig. Dis. Sci. 44, 1107–1116 (1999).

    CAS  PubMed  Google Scholar 

  46. Tennant, F. Why oral opioids may not be effective in a subset of chronic pain patients. Postgrad. Med. 128, 18–22 (2016).

    PubMed  Google Scholar 

  47. Crocker, J. A., Yu, H., Conaway, M., Tuskey, A. G. & Behm, B. W. Narcotic use and misuse in Crohn's disease. Inflamm. Bowel Dis. 20, 2234–2238 (2014).

    PubMed  Google Scholar 

  48. Surdea-Blaga, T., Baban, A. & Dumitrascu, D. Psychosocial determinants of irritable bowel syndrome. World J. Gastroenterol. 18, 616–626 (2012).

    PubMed  PubMed Central  Google Scholar 

  49. Targownik, L. E., Nugent, Z., Singh, H., Bugden, S. & Bernstein, C. N. The prevalence and predictors of opioid use in inflammatory bowel disease: a population-based analysis. Am. J. Gastroenterol. 109, 1613–1620 (2014).

    CAS  PubMed  Google Scholar 

  50. Edlund, M. J. et al. The role of opioid prescription in incident opioid abuse and dependence among individuals with chronic noncancer pain: the role of opioid prescription. Clin. J. Pain 30, 557–564 (2014).

    PubMed  PubMed Central  Google Scholar 

  51. Cook, S. F. et al. Gastrointestinal side effects in chronic opioid users: results from a population-based survey. Aliment. Pharmacol. Ther. 27, 1224–1232 (2008).

    CAS  PubMed  Google Scholar 

  52. Kraichely, R. E., Arora, A. S. & Murray, J. A. Opiate-induced oesophageal dysmotility. Aliment. Pharmacol. Ther. 31, 601–606 (2010).

    CAS  PubMed  Google Scholar 

  53. Gaertner, J. et al. Definitions and outcome measures of clinical trials regarding opioid-induced constipation: a systematic review. J. Clin. Gastroenterol. 49, 9–16 (2015).

    CAS  PubMed  Google Scholar 

  54. Mearin, F. et al. Bowel disorders. Gastroenterology 150, 1393–1407.e5 (2016).

    Google Scholar 

  55. Khemani, D. et al. Opioid analgesic use among patients presenting with acute abdominal pain and factors associated with surgical diagnoses. Neurogastroenterol. Motil. 29, e13000 (2016).

    Google Scholar 

  56. Rauck, R. L., Hong, K. J. & North, J. Opioid-induced constipation survey in patients with chronic noncancer pain. Pain Pract. 17, 329–335 (2017).

    PubMed  Google Scholar 

  57. Ratuapli, S. K. et al. Opioid-induced esophageal dysfunction (OIED) in patients on chronic opioids. Am. J. Gastroenterol. 110, 979–984 (2015).

    CAS  PubMed  Google Scholar 

  58. Fujioka, K. et al. Patients with short bowel on narcotics during 2 randomized trials have abdominal complaints independent of teduglutide. JPEN J. Parenter. Enteral. Nutr. http://dx.doi.org/10.1177/0148607116663481 (2016).

  59. Leppert, W. The impact of opioid analgesics on the gastrointestinal tract function and the current management possibilities. Contemp. Oncol. 16, 125–131 (2012).

    CAS  Google Scholar 

  60. Sobczak, M., Sałaga, M., Storr, M. A. & Fichna, J. Physiology, signaling, and pharmacology of opioid receptors and their ligands in the gastrointestinal tract: current concepts and future perspectives. J. Gastroenterol. 49, 24–45 (2014).

    CAS  PubMed  Google Scholar 

  61. Galligan, J. J. & Akbarali, H. I. Molecular physiology of enteric opioid receptors. Am. J. Gastroenterol. Suppl. 2, 17–21 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Holzer, P. New approaches to the treatment of opioid-induced constipation. Eur. Rev. Med. Pharmacol. Sci. 12 (Suppl. 1), 119–127 (2008).

    PubMed  PubMed Central  Google Scholar 

  63. Browning, K. N. & Travagli, R. A. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr. Physiol. 4, 1339–1368 (2014).

    PubMed  PubMed Central  Google Scholar 

  64. Barrett, K. E. New insights into the pathogenesis of intestinal dysfunction: secretory diarrhea and cystic fibrosis. World J. Gastroenterol. 6, 470–474 (2000).

    PubMed  PubMed Central  Google Scholar 

  65. Zhou, P., Li, T., Su, R. & Gong, Z. Effects of thienorphine on contraction of the guinea pig sphincter of Oddi, choledochus and gall bladder. Eur. J. Pharmacol. 737, 22–28 (2014).

    CAS  PubMed  Google Scholar 

  66. Joehl, R. J., Koch, K. L. & Nahrwold, D. L. Opioid drugs cause bile duct obstruction during hepatobiliary scans. Am. J. Surg. 147, 134–138 (1984).

    CAS  PubMed  Google Scholar 

  67. Mittal, R. K., Frank, E. B., Lange, R. C. & McCallum, R. W. Effects of morphine and naloxone on esophageal motility and gastric emptying in man. Dig. Dis. Sci. 31, 936–942 (1986).

    CAS  PubMed  Google Scholar 

  68. Penagini, R., Bartesaghi, B., Zannini, P., Negri, G. & Bianchi, P. A. Lower oesophageal sphincter hypersensitivity to opioid receptor stimulation in patients with idiopathic achalasia. Gut 34, 16–20 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Schoenfeld, P. S. Advances in IBS 2016: a review of current and emerging data. Gastroenterol. Hepatol. 12 (Suppl. 3), 1–11 (2016).

    Google Scholar 

  70. Cash, B. D., Lacy, B. E., Schoenfeld, P. S., Dove, L. S. & Covington, P. S. Safety of eluxadoline in patients with irritable bowel syndrome with diarrhea. Am. J. Gastroenterol. 112, 365–374 (2017).

    CAS  PubMed  Google Scholar 

  71. Chandok, N. & Watt, K. D. Pain management in the cirrhotic patient: the clinical challenge. Mayo Clin. Proc. 85, 451–458 (2010).

    PubMed  PubMed Central  Google Scholar 

  72. Bosilkovska, M., Walder, B., Besson, M., Daali, Y. & Desmeules, J. Analgesics in patients with hepatic impairment: pharmacology and clinical implications. Drugs 72, 1645–1669 (2012).

    CAS  PubMed  Google Scholar 

  73. Verbeeck, R. K. Pharmacokinetics and dosage adjustment in patients with hepatic dysfunction. Eur. J. Clin. Pharmacol. 64, 1147–1161 (2008).

    CAS  PubMed  Google Scholar 

  74. Hasselstrom, J. et al. The metabolism and bioavailability of morphine in patients with severe liver cirrhosis. Br. J. Clin. Pharmacol. 29, 289–297 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Soleimanpour, H., Safari, S., Shahsavari Nia, K., Sanaie, S. & Alavian, S. M. Opioid drugs in patients with liver disease: a systematic review. Hepat. Mon. 16, e32636 (2016).

    PubMed  PubMed Central  Google Scholar 

  76. Noble, M. et al. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst. Rev. 1, CD006605 (2010).

    Google Scholar 

  77. Ling, G. S., Paul, D., Simantov, R. & Pasternak, G. W. Differential development of acute tolerance to analgesia, respiratory depression, gastrointestinal transit and hormone release in a morphine infusion model. Life Sci. 45, 1627–1636 (1989).

    CAS  PubMed  Google Scholar 

  78. Schneider, J. P. & Kirsh, K. L. Defining clinical issues around tolerance, hyperalgesia, and addiction: a quantitative and qualitative outcome study of long-term opioid dosing in a chronic pain practice. J. Opioid Manag. 6, 385–395 (2010).

    PubMed  Google Scholar 

  79. Camilleri, M. et al. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol. Motil. 26, 1386–1395 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Harada, Y. et al. Mashiningan improves opioid-induced constipation in rats by activating cystic fibrosis transmembrane conductance regulator chloride channel. J. Pharmacol. Exp. Ther. 362, 78–84 (2017).

    CAS  PubMed  Google Scholar 

  81. Grunkemeier, D. M., Cassara, J. E., Dalton, C. B. & Drossman, D. A. The narcotic bowel syndrome: clinical features, pathophysiology, and management. Clin. Gastroenterol. Hepatol. 5, 1126–1139 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Keefer, L. et al. Centrally mediated disorders of gastrointestinal pain. Gastroenterology 150, 1408–1419 (2016).

    Google Scholar 

  83. Szigethy, E., Schwartz, M. & Drossman, D. Narcotic bowel syndrome and opioid-induced constipation. Curr. Gastroenterol. Rep. 16, 410 (2014).

    PubMed  Google Scholar 

  84. Drossman, D. & Szigethy, E. The narcotic bowel syndrome: a recent update. Am. J. Gastroenterol. Suppl. 2, 22–30 (2014).

    CAS  PubMed  Google Scholar 

  85. Drossman, D. A. Functional gastrointestinal disorders: history, pathophysiology, clinical features & Rome IV. Gastroenterology 150, 1262–1279.e2 (2016).

    Google Scholar 

  86. Low, Y., Clarke, C. F. & Huh, B. K. Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management. Singapore Med. J. 53, 357–360 (2012).

    PubMed  Google Scholar 

  87. Watkins, L. R. & Maier, S. F. Beyond neurons: evidence that immune and glial cells contribute to pathological pain states. Physiol. Rev. 82, 981–1011 (2002).

    CAS  PubMed  Google Scholar 

  88. Crain, S. M. & Shen, K. F. Antagonists of excitatory opioid receptor functions enhance morphine's analgesic potency and attenuate opioid tolerance/dependence liability. Pain 84, 121–131 (2000).

    CAS  PubMed  Google Scholar 

  89. Ossipov, M. H., Lai, J., King, T., Vanderah, T. W. & Porreca, F. Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers 80, 319–324 (2005).

    CAS  PubMed  Google Scholar 

  90. Kurlander, J. E. & Drossman, D. A. Diagnosis and treatment of narcotic bowel syndrome. Nat. Rev. Gastroenterol. Hepatol. 11, 410–418 (2014).

    CAS  PubMed  Google Scholar 

  91. Watkins, L. R., Milligan, E. D. & Maier, S. F. Glial activation: a driving force for pathological pain. Trends Neurosci. 24, 450–455 (2001).

    CAS  PubMed  Google Scholar 

  92. Rattan, A. K. & Tejwani, G. A. Effect of chronic treatment with morphine, midazolam and both together on dynorphin(1–13) levels in the rat. Brain Res. 754, 239–244 (1997).

    CAS  PubMed  Google Scholar 

  93. Agostini, S. et al. Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome. Gastroenterology 139, 553–563.e5 (2010).

    CAS  PubMed  Google Scholar 

  94. Hutchinson, M. R. et al. Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav. Immun. 24, 83–95 (2010).

    CAS  PubMed  Google Scholar 

  95. Hutchinson, M. R. et al. Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J. Neurosci. 32, 11187–11200 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Mattioli, T. A. et al. Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence. PLoS ONE 9, e97361 (2014).

    PubMed  PubMed Central  Google Scholar 

  97. Farmer, A. D., Ferdinand, E. & Aziz, Q. Opioids and the gastrointestinal tract — a case of narcotic bowel syndrome and literature review. J. Neurogastroenterol. Motil. 19, 94–98 (2013).

    PubMed  PubMed Central  Google Scholar 

  98. Kotalik, J. Controlling pain and reducing misuse of opioids: ethical considerations. Can. Fam. Physician 58, 381–385 (2012).

    PubMed  PubMed Central  Google Scholar 

  99. Dowell, D., Haegerich, T. M. & Chou, R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. JAMA 315, 1624–1645 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Murthy, V. H. Ending the opioid epidemic — a call to action. N. Engl. J. Med. 375, 2413–2415 (2016).

    PubMed  Google Scholar 

  101. Ballantyne, J. C. & Fleisher, L. A. Ethical issues in opioid prescribing for chronic pain. Pain 148, 365–367 (2010).

    PubMed  Google Scholar 

  102. Zgierska, A., Miller, M. & Rabago, D. Patient satisfaction, prescription drug abuse, and potential unintended consequences. JAMA 307, 1377–1378 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Kelly, S., Johnson, G. T. & Harbison, R. D. “Pressured to prescribe”: the impact of economic and regulatory factors on South-Eastern ED physicians when managing the drug seeking patient. J. Emerg. Trauma Shock 9, 58–63 (2016).

    PubMed  PubMed Central  Google Scholar 

  104. Kolodny, A. et al. The prescription opioid and heroin crisis: a public health approach to an epidemic of addiction. Annu. Rev. Publ. Health 36, 559–574 (2015).

    Google Scholar 

  105. Drossman, D. A. et al. Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome. Am. J. Gastroenterol. 107, 1426–1440 (2012).

    CAS  PubMed  Google Scholar 

  106. U.S. Food and Drug Administration. FDA requires strong warnings for opioid analgesics, prescription opioid cough products, and benzodiazepine labeling related to serious risks and death from combined use. U.S. Food and Drug Administration https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm518697.htm (2016).

  107. Tornblom, H. & Drossman, D. A. Centrally targeted pharmacotherapy for chronic abdominal pain. Neurogastroenterol. Motil. 27, 455–467 (2015).

    CAS  PubMed  Google Scholar 

  108. Dekel, R., Drossman, D. A. & Sperber, A. D. The use of psychotropic drugs in irritable bowel syndrome. Expert Opin. Investigat. Drugs 22, 329–339 (2013).

    CAS  Google Scholar 

  109. Stoicea, N. et al. Opioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin. Front. Pharmacol. 6, 104 (2015).

    PubMed  PubMed Central  Google Scholar 

  110. Arumugam, S., Lau, C. S. & Chamberlain, R. S. Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis. J. Pain Res. 9, 631–640 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Erlendson, M. J. et al. 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. Am. J. Drug Alcohol Abuse 43, 78–86 (2017).

    PubMed  Google Scholar 

  112. Gowing, L., Ali, R., White, J. M. & Mbewe, D. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst. Rev. 2, CD002025 (2017).

    PubMed  Google Scholar 

  113. Xie, C. et al. Efficacy and safety of antidepressants for the treatment of Irritable Bowel Syndrome: a meta-analysis. PLoS ONE 10, e0127815 (2015).

    PubMed  PubMed Central  Google Scholar 

  114. Thorkelson, G., Bielefeldt, K. & Szigethy, E. Empirically supported use of psychiatric medications in adolescents and adults with IBD. Inflamm. Bowel Dis. 22, 1509–1522 (2016).

    PubMed  Google Scholar 

  115. Cheng, Y. et al. Association between TLR2 and TLR4 gene polymorphisms and the susceptibility to Inflammatory Bowel Disease: a meta-analysis. PLoS ONE 10, e0126803 (2015).

    PubMed  PubMed Central  Google Scholar 

  116. Daghaghzadeh, H. et al. Efficacy of duloxetine add on in treatment of inflammatory bowel disease patients: a double-blind controlled study. J. Res. Med. Sci. 20, 595–601 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Talley, N. J. et al. Effect of amitriptyline and escitalopram on functional dyspepsia: a multicenter, randomized controlled study. Gastroenterology 149, 340–349.e342 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Talley, N. J. et al. Antidepressant therapy (imipramine and citalopram) for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial. Dig. Dis. Sci. 53, 108–115 (2008).

    CAS  PubMed  Google Scholar 

  119. Masand, P. S. et al. A double-blind, randomized, placebo-controlled trial of paroxetine controlled-release in irritable bowel syndrome. Psychosomatics 50, 78–86 (2009).

    CAS  PubMed  Google Scholar 

  120. Grover, M. & Camilleri, M. Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases. J. Gastroenterol. 48, 177–181 (2013).

    CAS  PubMed  Google Scholar 

  121. Grover, M. et al. Atypical antipsychotic quetiapine in the management of severe refractory functional gastrointestinal disorders. Dig. Dis. Sci. 54, 1284–1291 (2009).

    CAS  PubMed  Google Scholar 

  122. Gurusamy, K. S., Lusuku, C. & Davidson, B. R. Pregabalin for decreasing pancreatic pain in chronic pancreatitis. Cochrane Database Syst. Rev. 2, CD011522 (2016).

    PubMed  Google Scholar 

  123. Olesen, S. S. et al. Randomised clinical trial: pregabalin attenuates experimental visceral pain through sub-cortical mechanisms in patients with painful chronic pancreatitis. Aliment. Pharmacol. Ther. 34, 878–887 (2011).

    CAS  PubMed  Google Scholar 

  124. Gale, J. D. & Houghton, L. A. Alpha 2 delta (α2δ) Ligands, gabapentin and pregabalin: what is the evidence for potential use of these ligands in irritable bowel syndrome. Front. Pharmacol. 2, 28 (2011).

    PubMed  PubMed Central  Google Scholar 

  125. Takemura, Y. et al. Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis. Synapse 65, 668–676 (2011).

    CAS  PubMed  Google Scholar 

  126. Saito, Y. A. et al. A placebo-controlled trial of pregabalin for irritable bowel syndrome. Am. J. Gastroenterol. Suppl. 111, S236 (2016).

    Google Scholar 

  127. Paul, S. P. & Basude, D. Non-pharmacological management of abdominal painrelated functional gastrointestinal disorders in children. World J. Pediatr. 12, 389–398 (2016).

    CAS  PubMed  Google Scholar 

  128. Srinath, A. I., Walter, C., Newara, M. C. & Szigethy, E. M. Pain management in patients with inflammatory bowel disease: insights for the clinician. Therap. Adv. Gastroenterol. 5, 339–357 (2012).

    PubMed  PubMed Central  Google Scholar 

  129. Ford, A. C. et al. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis. Am. J. Gastroenterol. 109, 1350–1365 (2014).

    CAS  PubMed  Google Scholar 

  130. Ruepert, L. et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst. Rev. 8, CD003460 (2011).

    Google Scholar 

  131. Brennan, B. P. et al. Duloxetine in the treatment of irritable bowel syndrome: an open-label pilot study. Hum. Psychopharmacol. 24, 423–428 (2009).

    CAS  PubMed  Google Scholar 

  132. Kaplan, A., Franzen, M. D., Nickell, P. V., Ransom, D. & Lebovitz, P. J. An open-label trial of duloxetine in patients with irritable bowel syndrome and comorbid generalized anxiety disorder. Int. J. Psychiatry Clin. Pract. 18, 11–15 (2014).

    CAS  PubMed  Google Scholar 

  133. Lewis-Fernandez, R. et al. An open-label pilot study of duloxetine in patients with irritable bowel syndrome and comorbid major depressive disorder. J. Clin. Psychopharmacol. 36, 710–715 (2016).

    CAS  PubMed  Google Scholar 

  134. Lacy, B. E., Chey, W. D. & Lembo, A. J. New and emerging treatment options for Irritable Bowel Syndrome. Gastroenterol. Hepatol. 11 (Suppl. 2), 1–19 (2015).

    Google Scholar 

  135. Noyman-Veksler, G. et al. Role of pain-based catastrophizing in pain, disability, distress, and suicidal ideation. Psychiatry 80, 155–170 (2017).

    PubMed  Google Scholar 

  136. Cheng, C., Hui, W. & Lam, S. Perceptual style and behavioral pattern of individuals with functional gastrointestinal disorders. Health Psych. 19, 146–154 (2000).

    CAS  Google Scholar 

  137. Sandner-Kiesling, A. et al. Long-term efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of non-cancer chronic pain. Int. J. Clin. Pract. 64, 763–774 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Ford, A. C., Brenner, D. M. & Schoenfeld, P. S. Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and meta-analysis. Am. J. Gastroenterol. 108, 1566–1574 (2013).

    CAS  PubMed  Google Scholar 

  139. Mehta, N., O'Connell, K., Giambrone, G. P., Baqai, A. & Diwan, S. Efficacy of methylnaltrexone for the treatment of opiod-induced constipation: a meta-analysis and systematic review. Postgrad. Med. 128, 282–289 (2016).

    PubMed  Google Scholar 

  140. Kraft, M. D. Methylnaltrexone, a new peripherally acting mu-opioid receptor antagonist being evaluated for the treatment of postoperative ileus. Expert Opin. Invest. Drugs 17, 1365–1377 (2008).

    CAS  Google Scholar 

  141. Poulsen, J., Brock, C., Olesen, A. E., Nilsson, M. & Drewes, A. M. Evolving paradigms in the treatment of opioid-induced bowel dysfunction. Therap. Adv. Gastroenterol. 8, 360–372 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Sloots, C. E., Rykx, A., Cools, M., Kerstens, R. & De Pauw, M. Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid-induced constipation. Dig. Dis. Sci. 55, 2912–2921 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Sajid, M. S., Hebbar, M., Baig, M. K., Li, A. & Philipose, Z. Use of prucalopride for chronic constipation: a systematic review and meta-analysis of published randomized, controlled trials. J. Neurogastroenterol. Motil. 22, 412–422 (2016).

    PubMed  PubMed Central  Google Scholar 

  144. Nelson, A. D. & Camilleri, M. Opioid-induced constipation: advances and clinical guidance. Ther. Adv. Chron. Dis. 7, 121–134 (2016).

    CAS  Google Scholar 

  145. Argoff, C. E. et al. Consensus recommendations on initiating prescription therapies for opioid-induced constipation. Pain Med. 16, 2324–2337 (2015).

    PubMed  PubMed Central  Google Scholar 

  146. Ducrotte, P. & Causse, C. The Bowel Function Index: a new validated scale for assessing opioid-induced constipation. Curr. Med. Res. Opin. 28, 457–466 (2012).

    PubMed  Google Scholar 

  147. Slappendel, R., Simpson, K., Dubois, D. & Keininger, D. L. Validation of the PAC-SYM questionnaire for opioid-induced constipation in patients with chronic low back pain. Eur. J. Pain 10, 209–217 (2006).

    PubMed  Google Scholar 

  148. Keefer, L. & Mandal, S. The potential role of behavioral therapies in the management of centrally mediated abdominal pain. Neurogastroenterol. Motil. 27, 313–323 (2015).

    CAS  PubMed  Google Scholar 

  149. Eccleston, C., Morley, S. J. & Williams, A. C. Psychological approaches to chronic pain management: evidence and challenges. Br. J. Anaesth. 111, 59–63 (2013).

    CAS  PubMed  Google Scholar 

  150. Ehde, D. M., Dillworth, T. M. & Turner, J. A. Cognitive-behavioral therapy for individuals with chronic pain: efficacy, innovations, and directions for research. Am. Psychol. 69, 153–166 (2014).

    PubMed  Google Scholar 

  151. Kerns, R. D., Sellinger, J. & Goodin, B. R. Psychological treatment of chronic pain. Annu. Rev. Clin. Psychol. 7, 411–434 (2011).

    PubMed  Google Scholar 

  152. Tang, Q. L., Lin, G. Y. & Zhang, M. Q. Cognitive-behavioral therapy for the management of irritable bowel syndrome. World J. Gastroenterol. 19, 8605–8610 (2013).

    PubMed  PubMed Central  Google Scholar 

  153. Laird, K. T., Tanner-Smith, E. E., Russell, A. C., Hollon, S. D. & Walker, L. S. Short-term and long-term efficacy of psychological therapies for Irritable Bowel Syndrome: a systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 14, 937–947.e4 (2016).

    PubMed  Google Scholar 

  154. Altayar, O., Sharma, V., Prokop, L. J., Sood, A. & Murad, M. H. Psychological therapies in patients with irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials. Gastroenterol. Res. Pract. 2015, 549308 (2015).

    PubMed  PubMed Central  Google Scholar 

  155. Palsson, O. S. & Whitehead, W. E. Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist. Clin. Gastroenterol. Hepatol. 11, 208–216 (2013).

    PubMed  Google Scholar 

  156. Regueiro, M., Greer, J. B. & Szigethy, E. Etiology and treatment of pain and psychosocial issues in patients with inflammatory bowel diseases. Gastroenterology 152, 430–439.e4 (2017).

    PubMed  Google Scholar 

  157. Knowles, S. R., Monshat, K. & Castle, D. J. The efficacy and methodological challenges of psychotherapy for adults with inflammatory bowel disease: a review. Inflamm. Bowel Dis. 19, 2704–2715 (2013).

    PubMed  Google Scholar 

  158. Mikocka-Walus, A., Andrews, J. M. & Bampton, P. Cognitive behavioral therapy for IBD. Inflamm. Bowel Dis. 22, E5–E6 (2016).

    PubMed  Google Scholar 

  159. Lee, H. H., Choi, Y. Y. & Choi, M. G. The efficacy of hypnotherapy in the treatment of Irritable Bowel Syndrome: a systematic review and meta-analysis. J. Neurogastroenterol. Motil. 20, 152–162 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Webb, A. N., Kukuruzovic, R. H., Catto-Smith, A. G. & Sawyer, S. M. Hypnotherapy for treatment of irritable bowel syndrome. Cochrane Database Syst. Rev. 4, CD005110 (2007).

    Google Scholar 

  161. Aucoin, M., Lalonde-Parsi, M. J. & Cooley, K. Mindfulness-based therapies in the treatment of functional gastrointestinal disorders: a meta-analysis. Evid. Based Complement. Alternat. Med. 2014, 140724 (2014).

    PubMed  PubMed Central  Google Scholar 

  162. Goyal, M. et al. Meditation programs for psychological stress and well-being: a systematic review and meta-analysis. JAMA Intern. Med. 174, 357–368 (2014).

    PubMed  PubMed Central  Google Scholar 

  163. Bawa, F. L. et al. Does mindfulness improve outcomes in patients with chronic pain? Systematic review and meta-analysis. Br. J. Gen. Pract. 65, e387–e400 (2015).

    PubMed  PubMed Central  Google Scholar 

  164. Palsson, O. S. Hypnosis treatment of gastrointestinal disorders: a comprehensive review of the empirical evidence. Am. J. Clin. Hypn. 58, 134–158 (2015).

    PubMed  Google Scholar 

  165. Keefer, L. et al. Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis. Aliment. Pharmacol. Ther. 38, 761–771 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Jedel, S. et al. A randomized controlled trial of mindfulness-based stress reduction to prevent flare-up in patients with inactive ulcerative colitis. Digestion 89, 142–155 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Berrill, J. W., Sadlier, M., Hood, K. & Green, J. T. Mindfulness-based therapy for inflammatory bowel disease patients with functional abdominal symptoms or high perceived stress levels. J. Crohns Colitis 8, 945–955 (2014).

    PubMed  Google Scholar 

  168. Gerbarg, P. L. et al. The effect of breathing, movement, and meditation on psychological and physical symptoms and inflammatory biomarkers in Inflammatory Bowel Disease: a randomized controlled trial. Inflamm. Bowel Dis. 21, 2886–2896 (2015).

    PubMed  Google Scholar 

  169. Jones, M., Koloski, N., Boyce, P. & Talley, N. J. Pathways connecting cognitive behavioral therapy and change in bowel symptoms of IBS. J. Psychosom. Res. 70, 278–285 (2011).

    PubMed  Google Scholar 

  170. Chang, L. The role of stress on physiological responses and clinical symptoms in irritable bowel syndrome. Gastroenterology 140, 761–765 (2011).

    PubMed  PubMed Central  Google Scholar 

  171. Bonaz, B. L. & Bernstein, C. N. Brain-gut interactions in inflammatory bowel disease. Gastroenterology 144, 36–49 (2013).

    PubMed  Google Scholar 

  172. Carabotti, M., Scirocco, A., Maselli, M. & Severi, C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. 28, 203–209 (2015).

    PubMed  PubMed Central  Google Scholar 

  173. Uc, A. et al. Chronic pancreatitis in the 21st century — research challenges and opportunities: summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas 45, 1365–1375 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Palsson, O. S. & van Tilburg, M. Hypnosis and guided imagery treatment for gastrointestinal disorders: experience with scripted protocols developed at the University of North Carolina. Am. J. Clin. Hypn. 58, 5–21 (2015).

    PubMed  Google Scholar 

  175. Ljotsson, B. et al. Internet-delivered exposure-based treatment versus stress management for irritable bowel syndrome: a randomized trial. Am. J. Gastroenterol. 106, 1481–1491 (2011).

    PubMed  Google Scholar 

  176. Ljotsson, B. et al. Long-term follow-up of internet-delivered exposure and mindfulness based treatment for irritable bowel syndrome. Behav. Res. Ther. 49, 58–61 (2011).

    PubMed  Google Scholar 

  177. Eccleston, C. et al. Psychological therapies (Internet-delivered) for the management of chronic pain in adults. Cochrane Database Syst. Rev. 2, CD010152 (2014).

    Google Scholar 

  178. Krupnick, J. L. et al. The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. J. Consult. Clin. Psychol. 64, 532–539 (1996).

    CAS  PubMed  Google Scholar 

  179. Esquibel, A. Y. & Borkan, J. Doctors and patients in pain: conflict and collaboration in opioid prescription in primary care. Pain 155, 2575–2582 (2014).

    PubMed  Google Scholar 

  180. Bäckryd, E. “Professional Helper” or “Helping Professional?” The patient-physician relationship in the chronic pain setting, with special reference to the current opioid debate. J. Contin. Educ. Health Prof. 36, 133–137 (2016).

    PubMed  Google Scholar 

  181. Drossman, D. A. 2012 David Sun lecture: helping your patient by helping yourself — how to improve the patient-physician relationship by optimizing communication skills. Am. J. Gastroenterol. 108, 521–528 (2013).

    PubMed  Google Scholar 

  182. Frantsve, L. M. & Kerns, R. D. Patient-provider interactions in the management of chronic pain: current findings within the context of shared medical decision making. Pain Med. 8, 25–35 (2007).

    PubMed  Google Scholar 

  183. Reed-Knight, B., Claar, R. L., Schurman, J. V. & van Tilburg, M. A. Implementing psychological therapies for functional GI disorders in children and adults. Expert Rev. Gastroenterol. Hepatol. 10, 981–984 (2016).

    CAS  PubMed  Google Scholar 

  184. Martins, S. S. et al. Mood and anxiety disorders and their association with non-medical prescription opioid use and prescription opioid-use disorder: longitudinal evidence from the National Epidemiologic Study on Alcohol and Related Conditions. Psychol. Med. 42, 1261–1272 (2012).

    CAS  PubMed  Google Scholar 

  185. Wasan, A. D. et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology 123, 861–872 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Mason, M. J. et al. Depression moderates the relationship between pain and the nonmedical use of opioid medication among adult outpatients. J. Addict. Med. 10, 408–413 (2016).

    CAS  PubMed  Google Scholar 

  187. Arteta, J., Cobos, B., Hu, Y., Jordan, K. & Howard, K. Evaluation of how depression and anxiety mediate the relationship between pain catastrophizing and prescription opioid misuse in a chronic pain population. Pain Med. 17, 295–303 (2016).

    PubMed  Google Scholar 

  188. Rosenblum, A., Marsch, L. A., Joseph, H. & Portenoy, R. K. Opioids and the treatment of chronic pain: controversies, current status, and future directions. Exp. Clin. Psychopharmacol. 16, 405–416 (2008).

    PubMed  PubMed Central  Google Scholar 

  189. Cowan, D. T., Allan, L. G., Libretto, S. E. & Griffiths, P. Opioid drugs: a comparative survey of therapeutic and “street” use. Pain Med. 2, 193–203 (2001).

    CAS  PubMed  Google Scholar 

  190. Lee, E. B., An, W., Levin, M. E. & Twohig, M. P. An initial meta-analysis of Acceptance and Commitment Therapy for treating substance use disorders. Drug Alcohol Depend. 155, 1–7 (2015).

    PubMed  Google Scholar 

  191. Jones, C. M. Heroin use and heroin use risk behaviors among nonmedical users of prescription opioid pain relievers — United States, 2002–2004 and 2008–2010. Drug Alcohol Depend. 132, 95–100 (2013).

    PubMed  Google Scholar 

  192. Des Jarlais, D. C. et al. HIV incidence among injection drug users in New York City, 1990 to 2002: use of serologic test algorithm to assess expansion of HIV prevention services. Am. J. Publ. Health 95, 1439–1444 (2005).

    Google Scholar 

  193. Hagan, H. et al. Attribution of hepatitis C virus seroconversion risk in young injection drug users in 5 US cities. J. Infect. Dis. 201, 378–385 (2010).

    PubMed  Google Scholar 

  194. Paicius, R. M., Bernstein, C. A. & Lempert-Cohen, C. Peripheral nerve field stimulation in chronic abdominal pain. Pain Physician 9, 261–266 (2006).

    PubMed  Google Scholar 

  195. Kapural, L. & Jolly, S. Interventional pain management approaches for control of chronic pancreatic pain. Curr. Treat. Opt. Gastroenterol. 14, 360–370 (2016).

    Google Scholar 

  196. Simis, M. et al. Investigation of central nervous system dysfunction in chronic pelvic pain using magnetic resonance spectroscopy and noninvasive brain stimulation. Pain Pract. 15, 423–432 (2015).

    PubMed  Google Scholar 

  197. Moreno-Duarte, I. et al. Targeted therapies using electrical and magnetic neural stimulation for the treatment of chronic pain in spinal cord injury. Neuroimage 85, 1003–1013 (2014).

    PubMed  Google Scholar 

  198. Gray, A. M. et al. Deep brain stimulation as a treatment for neuropathic pain: a longitudinal study addressing neuropsychological outcomes. J. Pain 15, 283–292 (2014).

    PubMed  Google Scholar 

  199. Butler, S. F., Budman, S. H., Fanciullo, G. J. & Jamison, R. N. Cross validation of the Current Opioid Misuse Measure (COMM) to monitor chronic pain patients on opioid therapy. Clin. J. Pain 26, 770–776 (2010).

    PubMed  PubMed Central  Google Scholar 

  200. Butler, S. F., Fernandez, K., Benoit, C., Budman, S. H. & Jamison, R. N. Validation of the Revised Screener and Opioid Assessment for Patients with Pain (SOAPP-R). J. Pain 9, 360–372 (2008).

    PubMed  PubMed Central  Google Scholar 

  201. Bao, Y. et al. Prescription drug monitoring programs are associated with sustained reductions in opioid prescribing by physicians. Health Aff. 35, 1045–1051 (2016).

    Google Scholar 

  202. Kovitwanichkanont, T. & Day, C. A. Prescription opioid misuse and public health approach in Australia. Subst. Use Misuse http://dx.doi.org/10.1080/10826084.2017.1305415 (2017).

  203. European Monitoring Centre for Drugs and Drug Addiction. Our activities — ongoing projects and programmes. European Monitoring Centre for Drugs and Drug Addiction http://www.emcdda.europa.eu/activities (2017).

  204. Novak, S. P. et al. Nonmedical use of prescription drugs in the European Union. BMC Psychiatry 16, 274 (2016).

    PubMed  PubMed Central  Google Scholar 

  205. University of Wisconsin–Madison Pain & Policy Studies Group. Custom consumption graphs for opioid medicines. Pain & Policy Studies Group https://ppsg-chart.medicine.wisc.edu/ (2017).

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Acknowledgements

M.K. is supported by NIH Award Number T32NR009759.

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E.S. is a consultant for AbbVie and has received royalties from American Psychiatric Association Publishing, grant support from the NIH, the Crohn's & Colitis Foundation and the Bruce and Cynthia Sherman Foundation, and honoraria for educational talks for Imedex and the American Academy of Child and Adolescent Psychiatry. D.D. is President of the Rome Foundation and has been on advisory boards for Allergan, AstraZeneca, Ironwood and Shionogi in the past year.

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Szigethy, E., Knisely, M. & Drossman, D. Opioid misuse in gastroenterology and non-opioid management of abdominal pain. Nat Rev Gastroenterol Hepatol 15, 168–180 (2018). https://doi.org/10.1038/nrgastro.2017.141

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