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Pain Management in Chronic Pancreatitis: Summary of Clinical Practice, Current Challenges and Potential Contribution of the M-ANNHEIM Classification

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Abstract

Abdominal pain, diarrhea with weight loss, and endocrine insufficiency represent the dominant symptoms of chronic pancreatitis (CP). High intensity of pain and constant pain have been shown to reduce quality of life in CP and may result in disability and increased health resource utilization. Various basic challenges and unanswered questions still exist regarding the treatment of pain in CP. Recently, limited evidence has been gained that early surgery for painful disease might be associated with better treatment results. Thus, timing of pancreatic surgery in painful disease represents a major issue that needs to be clarified in future studies. In this context, surveillance of patients is necessary in clinical practice. It appears that a generally accepted classification of the disease represents a major requirement for inter-institutional comparison of data with future progress in clinical research. Among recently proposed classification systems, the M-ANNHEIM classification system of CP with its recently presented M-ANNHEIM Surgery Score might be a useful tool to picture the course of the disease and to monitor treatment results. Future research is required to clarify the possible role of this system in the management of pain in CP. In the present article, we provide an overview of current status, challenges, and unanswered questions in the treatment of pain in CP, and we demonstrate the potential benefits of the M-ANNHEIM classification system in the management of painful CP.

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References

  1. Ammann RW, Akovbiantz A, Largiader F, Schueler G. Course and outcome of chronic pancreatitis. Longitudinal study of a mixed medical-surgical series of 245 patients. Gastroenterology. 1984;86:820–8.

    CAS  PubMed  Google Scholar 

  2. Lankisch PG, Lohr-Happe A, Otto J, Creutzfeldt W. Natural course in chronic pancreatitis. Digestion. 1993;54:148–55.

    Article  CAS  PubMed  Google Scholar 

  3. Layer P, Yamamoto H, Kalthoff L, Clain JE, Bakken LJ, DiMagno EP. The different courses of early and late onset idiopathic and alcoholic chronic pancreatitis. Gastroenterology. 1994;107:1481–7.

    Article  CAS  PubMed  Google Scholar 

  4. Ammann RW, Heitz PU, Klöppel G. Course of alcoholic chronic pancreatitis: a prospective clinicomorphological long-term study. Gastroenterology. 1996;111:224–31.

    Article  CAS  PubMed  Google Scholar 

  5. Ammann RW, Muellhaupt B. The natural history of pain in alcoholic chronic pancreatitis. Gastroenterology. 1999;116:1132–40.

    Article  CAS  PubMed  Google Scholar 

  6. Lankisch PG, Seidensticker F, Otto J, Lübbers H, Mahlke R, Stöckmann F, Fölsch UR, Creutzfeldt W. Secretin-pancreozymin test (SPT) and endoscopic retrograde cholangiopancreatography (ERCP): both are necessary for diagnosing or excluding chronic pancreatitis. Pancreas. 1996;12:149–52.

    Article  CAS  PubMed  Google Scholar 

  7. Löhr JM. Exocrine pancreatic insufficiency. Bremen: UNI-MED Verlag AG; 2007.

    Google Scholar 

  8. Schneider A, Löhr JM, Singer MV. The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classifications of the disease. J Gastroenterol. 2007;42:101–19.

    Article  PubMed  Google Scholar 

  9. Kempeneers MA, Issa Y, Verdonk RC, Bruno M, Fockens P, van Goor H, Alofs E, Bollen TL, Bouwense S, van Dalen A, van Dieren S, van Dullemen HM, van Geenen EJ, Hoge C, van Hooft JE, Kager LM, Keulemans Y, Nooijen LE, Poley JW, Seerden TCJ, Tan A, Thijs W, Timmer R, Vleggaar F, Witteman B, Ahmed Ali U, Besselink MG, Boermeester MA, van Santvoort HC, Dutch Pancreatitis Study G. Pain patterns in chronic pancreatitis: a nationwide longitudinal cohort study. Gut. 2020;0:1–10.

  10. Lohr JM, Dominguez-Munoz E, Rosendahl J, Besselink M, Mayerle J, Lerch MM, Haas S, Akisik F, Kartalis N, Iglesias-Garcia J, Keller J, Boermeester M, Werner J, Dumonceau JM, Fockens P, Drewes A, Ceyhan G, Lindkvist B, Drenth J, Ewald N, Hardt P, de Madaria E, Witt H, Schneider A, Manfredi R, Brondum FJ, Rudolf S, Bollen T, Bruno M. HaPan EUUEGWG: United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU). United Eur Gastroenterol J. 2017;5:153–99.

    Article  Google Scholar 

  11. Mullady DK, Yadav D, Amann ST, O’Connell MR, Barmada MM, Elta GH, Scheiman JM, Wamsteker EJ, Chey WD, Korneffel ML, Weinman BM, Slivka A, Sherman S, Hawes RH, Brand RE, Burton FR, Lewis MD, Gardner TB, Gelrud A, DiSario J, Baillie J, Banks PA, Whitcomb DC, Anderson MA, Consortium N. Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut. 2011;60:77–84.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Girdwood AH, Marks IN, Bornman PC, Kottler RE, Cohen M. Does progressive pancreatic insufficiency limit pain in calcific pancreatitis with duct stricture or continued alcohol insult? J Clin Gastroenterol. 1981;3:241–5.

    Article  CAS  PubMed  Google Scholar 

  13. Hirth M, Weiss C, Hardt P, Gubergrits N, Hartel N, Ebert MP, Schneider A. Analysis of the course of chronic pancreatitis: pancreatic burnout rates are only increased in a subgroup of patients with alcoholic chronic pancreatitis. Pancreas. 2019;48:726–33.

    Article  PubMed  Google Scholar 

  14. Poulsen JL, Olesen SS, Malver LP, Frokjaer JB, Drewes AM. Pain and chronic pancreatitis: a complex interplay of multiple mechanisms. World J Gastroenterol. 2013;19:7282–91.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Bang UC, Benfield T, Hyldstrup L, Bendtsen F, Beck Jensen JE. Mortality, cancer, and comorbidities associated with chronic pancreatitis: a Danish nationwide matched-cohort study. Gastroenterology. 2014;146:989–94.

    Article  PubMed  Google Scholar 

  16. Drewes AM, Krarup AL, Detlefsen S, Malmstrom ML, Dimcevski G, Funch-Jensen P. Pain in chronic pancreatitis: the role of neuropathic pain mechanisms. Gut. 2008;57:1616–27.

    Article  CAS  PubMed  Google Scholar 

  17. Drewes AM, Kempeneers MA, Andersen DK, Arendt-Nielsen L, Besselink MG, Boermeester MA, Bouwense S, Bruno M, Freeman M, Gress TM, van Hooft JE, Morlion B, Olesen SS, van Santvoort H, Singh V, Windsor J. Controversies on the endoscopic and surgical management of pain in patients with chronic pancreatitis: pros and cons! Gut. 2019;68:1343–51.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wilcox CM, Yadav D, Ye T, Gardner TB, Gelrud A, Sandhu BS, Lewis MD, Al-Kaade S, Cote GA, Forsmark CE, Guda NM, Conwell DL, Banks PA, Muniraj T, Romagnuolo J, Brand RE, Slivka A, Sherman S, Wisniewski SR, Whitcomb DC, Anderson MA. Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings. Clin Gastroenterol Hepatol. 2015;13:552–60 (quiz e528–559).

    Article  PubMed  Google Scholar 

  19. Ebbehoj N, Borly L, Madsen P, Svendsen LB. Pancreatic tissue pressure and pain in chronic pancreatitis. Pancreas. 1986;1:556–8.

    Article  CAS  PubMed  Google Scholar 

  20. Demir IE, Friess H, Ceyhan GO. Neural plasticity in pancreatitis and pancreatic cancer. Nat Rev Gastroenterol Hepatol. 2015;12:649–59.

    Article  CAS  PubMed  Google Scholar 

  21. Drewes AM, Bouwense SAW, Campbell CM, Ceyhan GO, Delhaye M, Demir IE, Garg PK, van Goor H, Halloran C, Isaji S, Neoptolemos JP, Olesen SS, Palermo T, Pasricha PJ, Sheel A, Shimosegawa T, Szigethy E, Whitcomb DC, Yadav D. Working group for the International Consensus Guidelines for Chronic P: guidelines for the understanding and management of pain in chronic pancreatitis. Pancreatology. 2017;17:720–31.

    Article  PubMed  Google Scholar 

  22. Olesen SS, Bouwense SA, Wilder-Smith OH, van Goor H, Drewes AM. Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial. Gastroenterology. 2011;141:536–43.

    Article  CAS  PubMed  Google Scholar 

  23. 23WHO: Cancer, pain relief and palliative care. Geneva: World Health Organization WHO technical report series 1990; No. 408

  24. Di Sebastiano P, Weigand MA, Köninger J, Di Mola FF, Friess H, Büchler MW. Conservative treatment of pain in chronic pancreatitis: guidelines for clinical routine. In: Dominguez-Munoz JE, editor. Clinical pancreatology for practising gastroenterologists and surgeons. Oxford: Blackwell Publishing Ltd; 2005. p. 273–9.

    Google Scholar 

  25. Wilder-Smith CH, 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. 1999;44:1107–16.

    Article  CAS  PubMed  Google Scholar 

  26. Brock C, Olesen SS, Olesen AE, Frokjaer JB, Andresen T, Drewes AM. Opioid-induced bowel dysfunction: pathophysiology and management. Drugs. 2012;72:1847–65.

    Article  CAS  PubMed  Google Scholar 

  27. O’Brien T, Christrup LL, Drewes AM, Fallon MT, Kress HG, McQuay HJ, Mikus G, Morlion BJ, Perez-Cajaraville J, Pogatzki-Zahn E, Varrassi G, Wells JC. European Pain Federation position paper on appropriate opioid use in chronic pain management. Eur J Pain. 2017;21:3–19.

    Article  PubMed  Google Scholar 

  28. Drewes AM, Jensen RD, Nielsen LM, Droney J, Christrup LL, Arendt-Nielsen L, Riley J, Dahan A. Differences between opioids: pharmacological, experimental, clinical and economical perspectives. Br J Clin Pharmacol. 2013;75:60–78.

    Article  CAS  PubMed  Google Scholar 

  29. Eisenach JC, Carpenter R, Curry R. Analgesia from a peripherally active kappa-opioid receptor agonist in patients with chronic pancreatitis. Pain. 2003;101:89–95.

    Article  CAS  PubMed  Google Scholar 

  30. Sengupta JN, Su X, Gebhart GF. Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon. Gastroenterology. 1996;111:968–80.

    Article  CAS  PubMed  Google Scholar 

  31. Kurlander JE, Drossman DA. Diagnosis and treatment of narcotic bowel syndrome. Nat Rev Gastroenterol Hepatol. 2014;11:410–8.

    Article  CAS  PubMed  Google Scholar 

  32. Szigethy E, Schwartz M, Drossman D. Narcotic bowel syndrome and opioid-induced constipation. Curr Gastroenterol Rep. 2014;16:410.

    Article  PubMed  Google Scholar 

  33. Olesen AE, Brokjaer A, Fisher IW, Larsen IM. Pharmacological challenges in chronic pancreatitis. World J Gastroenterol. 2013;19:7302–7.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dumonceau JM, Delhaye M, Tringali A, Dominguez-Munoz JE, Poley JW, Arvanitaki M, Costamagna G, Costea F, Deviere J, Eisendrath P, Lakhtakia S, Reddy N, Fockens P, Ponchon T, Bruno M. Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2012;44:784–800.

    Article  PubMed  Google Scholar 

  35. Hoffmeister A, Mayerle J, Beglinger C, Buchler MW, Bufler P, Dathe K, Folsch UR, Friess H, Izbicki J, Kahl S, Klar E, Keller J, Knoefel WT, Layer P, Loehr M, Meier R, Riemann JF, Runzi M, Schmid RM, Schreyer A, Tribl B, Werner J, Witt H, Mossner J, Lerch MM. members of the guideline c: English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis. Z Gastroenterol. 2015;53:1447–95.

    Article  CAS  PubMed  Google Scholar 

  36. Martinez J, Abad-Gonzalez A, Aparicio JR, Aparisi L, Boadas J, Boix E, de Las HG, Dominguez-Munoz E, Farre A, Fernandez-Cruz L, Gomez L, Iglesias-Garcia J, Garcia-Malpartida K, Guarner L, Larino-Noia J, Lluis F, Lopez A, Molero X, Moreno-Perez O, Navarro S, Palazon JM, Perez-Mateo M, Sabater L, Sastre Y, Vaquero E. de-Madaria E: The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis). Pancreatology. 2013;13:8–17.

    Article  CAS  PubMed  Google Scholar 

  37. de-Madaria E, Abad-Gonzalez A, Aparicio JR, Aparisi L, Boadas J, Boix E, de-Las Heras G, Dominguez-Munoz E, Farre A, Fernandez-Cruz L, Gomez L, Iglesias-Garcia J, Garcia-Malpartida K, Guarner L, Larino-Noia J, Lluis F, Lopez A, Molero X, Moreno-Perez O, Navarro S, Palazon JM, Perez-Mateo M, Sabater L, Sastre Y, Vaquero EC, Martinez J. The Spanish Pancreatic Club’s recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment). Pancreatology. 2013;13:18–28.

    Article  CAS  PubMed  Google Scholar 

  38. Delhaye M, Van Steenbergen W, Cesmeli E, Pelckmans P, Putzeys V, Roeyen G, Berrevoet F, Scheers I, Ausloos F, Gast P, Ysebaert D, Plat L, van der Wijst E, Hans G, Arvanitakis M, Deprez PH. Belgian consensus on chronic pancreatitis in adults and children: statements on diagnosis and nutritional, medical, and surgical treatment. Acta Gastro-enterol Belg. 2014;77:47–65.

    Google Scholar 

  39. Frulloni L, Falconi M, Gabbrielli A, Gaia E, Graziani R, Pezzilli R, Uomo G, Andriulli A, Balzano G, Benini L, Calculli L, Campra D, Capurso G, Cavestro GM, De Angelis C, Ghezzo L, Manfredi R, Malesci A, Mariani A, Mutignani M, Ventrucci M, Zamboni G, Amodio A, Vantini I, Italian Association for the Study of the P, Bassi C, Delle Fave G, Frulloni L, Vantini I, Falconi M, Frulloni L, Gabbrielli A, Graziani R, Pezzilli R, Capurso IV, Cavestro GM, De Angelis C, Falconi M, Gaia E, Ghezzo L, Gabbrielli A, Graziani R, Manfredi R, Malesci A, Mariani A, Mutignani M, Pezzilli R, Uomo G, Ventrucci M, Zamboni G, Vantini I, Magarini F, Albarello L, Alfieri S, Amodio A, Andriulli A, Anti M, Arcidiacono P, Baiocchi L, Balzano G, Benini L, Berretti D, Boraschi P, Buscarini E, Calculli L, Carroccio A, Campra D, Celebrano MR, Capurso G, Casadei R, Cavestro GM, Chilovi F, Conigliaro R, Dall’Oglio L, De Angelis C, De Boni M, De Pretis G, Di Priolo S, Di Sebastiano PL, Doglietto GB, Falconi M, Filauro M, Frieri G, Frulloni L, Fuini A, Gaia E, Ghezzo L, Gabbrielli A, Graziani R, Loriga P, Macarri G, Manes G, Manfredi R, Malesci A, Mariani A, Massucco P, Milani S, Mutignani M, Pasquali C, Pederzoli P, Pezzilli R, Pietrangeli M, Rocca R, Russello D, Siquini W, Traina M, Uomo G, Veneroni L, Ventrucci M, Zilli M, Zamboni G. Italian consensus guidelines for chronic pancreatitis. Dig Liver Dis. 2010;42(Suppl 6):S381-406.

    Article  PubMed  Google Scholar 

  40. Rana MV, Candido KD, Raja O, Knezevic NN. Celiac plexus block in the management of chronic abdominal pain. Curr Pain Headache Rep. 2014;18:394.

    Article  PubMed  Google Scholar 

  41. Moole H, Jaeger A, Bechtold ML, Forcione D, Taneja D, Puli SR. Success of extracorporeal shock wave lithotripsy in chronic calcific pancreatitis management: a meta-analysis and systematic review. Pancreas. 2016;45:651–8.

    Article  PubMed  Google Scholar 

  42. Kleeff J, Stoss C, Mayerle J, Stecher L, Maak M, Simon P, Nitsche U, Friess H. Evidence-based surgical treatments for chronic pancreatitis. Dtsch Arztebl Int. 2016;113:489–96.

    PubMed  PubMed Central  Google Scholar 

  43. Demir IE, Tieftrunk E, Maak M, Friess H, Ceyhan GO. Pain mechanisms in chronic pancreatitis: of a master and his fire. Langenbeck’s Arch Surg Dtsch Ges Chir. 2011;396:151–60.

    Article  Google Scholar 

  44. Strum WB. Abstinence in alcoholic chronic pancreatitis. Effect on pain and outcome. J Clin Gastroenterol. 1995;20:37–41.

    Article  CAS  PubMed  Google Scholar 

  45. Tjora E, Dimcevski G, Haas SL, Erchinger F, Vujasinovic M, Lohr M, Nojgaard C, Novovic S, Zalite IO, Pukitis A, Hauge T, Waage A, Roug S, Kalaitzakis E, Lindkvist B, Olesen SS, Engjom T. Scandinavian Baltic Pancreatic C: patient reported exposure to smoking and alcohol abuse are associated with pain and other complications in patients with chronic pancreatitis. Pancreatology. 2020;20:844–51.

    Article  PubMed  Google Scholar 

  46. Maisonneuve P, Lowenfels AB, Müllhaupt B, Cavallini G, Lankisch PG, Andersen JR, DiMagno EP, Andrén-Sandberg A, Domellöf L, Frulloni L, Ammann RW. Cigarette smoking accelerates progression of alcoholic chronic pancreatitis. Gut. 2005;54:510–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bhardwaj P, Garg PK, Maulik SK, Saraya A, Tandon RK, Acharya SK. A randomized controlled trial of antioxidant supplementation for pain relief in patients with chronic pancreatitis. Gastroenterology. 2009;136(149–159):e142.

    Google Scholar 

  48. Siriwardena AK, Mason JM, Sheen AJ, Makin AJ, Shah NS. Antioxidant therapy does not reduce pain in patients with chronic pancreatitis: the ANTICIPATE study. Gastroenterology. 2012;143(655–663):e651.

    Google Scholar 

  49. Uc A, Andersen DK, Bellin MD, Bruce JI, Drewes AM, Engelhardt JF, Forsmark CE, Lerch MM, Lowe ME, Neuschwander-Tetri BA, O’Keefe SJ, Palermo TM, Pasricha P, Saluja AK, Singh VK, Szigethy EM, Whitcomb DC, Yadav D, Conwell DL. Chronic pancreatitis in the 21st century—research challenges and opportunities: summary of a national institute of diabetes and digestive and kidney diseases workshop. Pancreas. 2016;45:1365–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Attal N, Fermanian C, Fermanian J, Lanteri-Minet M, Alchaar H, Bouhassira D. Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion? Pain. 2008;138:343–53.

    Article  CAS  PubMed  Google Scholar 

  51. Baron R, Forster M, Binder A. Subgrouping of patients with neuropathic pain according to pain-related sensory abnormalities: a first step to a stratified treatment approach. Lancet Neurol. 2012;11:999–1005.

    Article  PubMed  Google Scholar 

  52. de Rijk FE, Kempeneers MA, Bruno MJ, Besselink MG, van Goor H, Boermeester MA, van Geenen EJ, van Hooft JE, van Santvoort HC, Verdonk RC, Dutch Pancreatitis Study G. Suboptimal care for chronic pancreatitis patients revealed by moderate to low adherence to the United European Gastroenterology evidence-based guidelines (HaPanEU): A Netherlands nationwide analysis. United Eur Gastroenterol J. 2020;8:764–74.

    Article  Google Scholar 

  53. Cahen DL, van Berkel AM, Oskam D, Rauws EA, Weverling GJ, Huibregtse K, Bruno MJ. Long-term results of endoscopic drainage of common bile duct strictures in chronic pancreatitis. Eur J Gastroenterol Hepatol. 2005;17:103–8.

    Article  PubMed  Google Scholar 

  54. Cahen DL, Gouma DJ, Nio Y, Rauws EA, Boermeester MA, Busch OR, Stoker J, Lameris JS, Dijkgraaf MG, Huibregtse K, Bruno MJ. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis. N Engl J Med. 2007;356:676–84.

    Article  CAS  PubMed  Google Scholar 

  55. Cahen DL, Gouma DJ, Laramee P, Nio Y, Rauws EA, Boermeester MA, Busch OR, Fockens P, Kuipers EJ, Pereira SP, Wonderling D, Dijkgraaf MG, Bruno MJ. Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis. Gastroenterology. 2011;141:1690–5.

    Article  PubMed  Google Scholar 

  56. Dite P, Ruzicka M, Zboril V, Novotny I. A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis. Endoscopy. 2003;35:553–8.

    Article  CAS  PubMed  Google Scholar 

  57. Nealon WH, Thompson JC. Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression A longitudinal prospective analysis of the modified puestow procedure. Ann Surg. 1993;217:458–66 (discussion 466-458).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ahmed Ali U, Nieuwenhuijs VB, van Eijck CH, Gooszen HG, van Dam RM, Busch OR, Dijkgraaf MG, Mauritz FA, Jens S, Mast J, van Goor H, Boermeester MA, Dutch Pancreatitis Study G. Clinical outcome in relation to timing of surgery in chronic pancreatitis: a nomogram to predict pain relief. Arch Surg. 2012;147:925–32.

    PubMed  Google Scholar 

  59. Riediger H, Adam U, Fischer E, Keck T, Pfeffer F, Hopt UT, Makowiec F. Long-term outcome after resection for chronic pancreatitis in 224 patients. J Gastrointest Surg. 2007;11:949–59 (discussion 959–960).

    Article  PubMed  Google Scholar 

  60. Yang CJ, Bliss LA, Schapira EF, Freedman SD, Ng SC, Windsor JA, Tseng JF. Systematic review of early surgery for chronic pancreatitis: impact on pain, pancreatic function, and re-intervention. J Gastrointest Surg. 2014;18:1863–9.

    Article  PubMed  Google Scholar 

  61. Issa Y, Kempeneers MA, Bruno MJ, Fockens P, Poley JW, Ahmed Ali U, Bollen TL, Busch OR, Dejong CH, van Duijvendijk P, van Dullemen HM, van Eijck CH, van Goor H, Hadithi M, Haveman JW, Keulemans Y, Nieuwenhuijs VB, Poen AC, Rauws EA, Tan AC, Thijs W, Timmer R, Witteman BJ, Besselink MG, van Hooft JE, van Santvoort HC, Dijkgraaf MG, Boermeester MA, Dutch Pancreatitis Study G. Effect of early surgery vs endoscopy-first approach on pain in patients with chronic pancreatitis: the ESCAPE Randomized Clinical Trial. JAMA. 2020;323:237–47.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kempeneers MA, Issa Y, Ali UA, Baron RD, Besselink MG, Buchler M, Erkan M, Fernandez-Del Castillo C, Isaji S, Izbicki J, Kleeff J, Laukkarinen J, Sheel ARG, Shimosegawa T, Whitcomb DC, Windsor J, Miao Y, Neoptolemos J, Boermeester MA. Working group for the international consensus guidelines for chronic P: international consensus guidelines for surgery and the timing of intervention in chronic pancreatitis. Pancreatology. 2020;20:149–57.

    Article  CAS  PubMed  Google Scholar 

  63. Olesen SS, Juel J, Nielsen AK, Frokjaer JB, Wilder-Smith OH, Drewes AM. Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials. Pancreatology. 2014;14:497–502.

    Article  PubMed  Google Scholar 

  64. Balliet WE, Edwards-Hampton S, Borckardt JJ, Morgan K, Adams D, Owczarski S, Madan A, Galloway SK, Serber ER, Malcolm R. Depressive symptoms, pain, and quality of life among patients with nonalcohol-related chronic pancreatitis. Pain Res Treat. 2012;2012:978646.

    PubMed  PubMed Central  Google Scholar 

  65. Gardner TB, Kennedy AT, Gelrud A, Banks PA, Vege SS, Gordon SR, Lacy BE. Chronic pancreatitis and its effect on employment and health care experience: results of a prospective American multicenter study. Pancreas. 2010;39:498–501.

    Article  PubMed  Google Scholar 

  66. Wassef W, DeWitt J, McGreevy K, Wilcox M, Whitcomb D, Yadav D, Amann S, Mishra G, Alkaade S, Romagnuolo J, Stevens T, Vargo J, Gardner T, Singh V, Park W, Hartigan C, Barton B, Bova C. Pancreatitis quality of life instrument: a psychometric evaluation. Am J Gastroenterol. 2016;111:1177–86.

    Article  PubMed  Google Scholar 

  67. Pezzilli R, Fantini L. Chronic pancreatitis: assessing the quality of life. JOP. 2005;6:406–9.

    PubMed  Google Scholar 

  68. Fitzsimmons D, Johnson CD, George S, Payne S, Sandberg AA, Bassi C, Beger HG, Birk D, Buchler MW, Dervenis C, FernandezCruz L, Friess H, Grahm AL, Jeekel J, Laugier R, Meyer D, Singer MW, Tihanyi T. Development of a disease specific quality of life (QoL) questionnaire module to supplement the EORTC core cancer QoL questionnaire, the QLQ-C30 in patients with pancreatic cancer. EORTC Study Group on Quality of Life. Eur J Cancer. 1999;35:939–41.

    Article  CAS  PubMed  Google Scholar 

  69. Bloechle C, Izbicki JR, Knoefel WT, Kuechler T, Broelsch CE. Quality of life in chronic pancreatitis–results after duodenum-preserving resection of the head of the pancreas. Pancreas. 1995;11:77–85.

    Article  CAS  PubMed  Google Scholar 

  70. Seicean A, Grigorescu M, Tantau M, Dumitrascu DL, Pop D, Mocan T. Pain in chronic pancreatitis: assessment and relief through treatment. Rom J Gastroenterol. 2004;13:9–15.

    PubMed  Google Scholar 

  71. Teo K, Johnson MH, Truter S, Pandanaboyana S, Windsor JA. Pain assessment in chronic pancreatitis: a comparative review of methods. Pancreatology. 2016;16:931–9.

    Article  CAS  PubMed  Google Scholar 

  72. Teo K, Johnson MH, Drewes AM, Windsor JA. A comprehensive pain assessment tool (COMPAT) for chronic pancreatitis: development, face validation and pilot evaluation. Pancreatology. 2017;17:706–19.

    Article  CAS  PubMed  Google Scholar 

  73. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152:S2-15.

    Article  PubMed  Google Scholar 

  74. Kuhlmann L, Olesen SS, Gronlund D, Olesen AE, Phillips AE, Faghih M, Drewes AM. Patient and disease characteristics associate with sensory testing results in chronic pancreatitis. Clin J Pain. 2019;35:786–93.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Phillips AE, Faghih M, Kuhlmann L, Larsen IM, Drewes AM, Singh VK, Yadav D, Olesen SS. Pancreatic quantitative sensory testing C: a clinically feasible method for the assessment and characterization of pain in patients with chronic pancreatitis. Pancreatology. 2020;20:25–34.

    Article  PubMed  Google Scholar 

  76. Olesen SS, Graversen C, Bouwense SA, van Goor H, Wilder-Smith OH, Drewes AM. Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis. PLoS ONE. 2013;8:e57963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bouwense SA, Olesen SS, Drewes AM, Poley JW, van Goor H, Wilder-Smith OH. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial. PLoS ONE. 2012;7:e42096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bouwense SA, Buscher HC, van Goor H, Wilder-Smith OH. Has central sensitization become independent of nociceptive input in chronic pancreatitis patients who fail thoracoscopic splanchnicectomy? Reg Anesth Pain Med. 2011;36:531–6.

    Article  PubMed  Google Scholar 

  79. Staahl C, Dimcevski G, Andersen SD, Thorsgaard N, Christrup LL, Arendt-Nielsen L, Drewes AM. Differential effect of opioids in patients with chronic pancreatitis: an experimental pain study. Scand J Gastroenterol. 2007;42:383–90.

    Article  CAS  PubMed  Google Scholar 

  80. Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, Cleeland C, Dionne R, Farrar JT, Galer BS, Hewitt DJ, Jadad AR, Katz NP, Kramer LD, Manning DC, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robinson JP, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Witter J. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain. 2003;106:337–45.

    Article  PubMed  Google Scholar 

  81. Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J. Immpact: Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113:9–19.

    Article  PubMed  Google Scholar 

  82. Edwards RR, Dworkin RH, Turk DC, Angst MS, Dionne R, Freeman R, Hansson P, Haroutounian S, Arendt-Nielsen L, Attal N, Baron R, Brell J, Bujanover S, Burke LB, Carr D, Chappell AS, Cowan P, Etropolski M, Fillingim RB, Gewandter JS, Katz NP, Kopecky EA, Markman JD, Nomikos G, Porter L, Rappaport BA, Rice AS, Scavone JM, Scholz J, Simon LS, Smith SM, Tobias J, Tockarshewsky T, Veasley C, Versavel M, Wasan AD, Wen W, Yarnitsky D. Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations. Pain. 2016;157:1851–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bagul A, Sirivardena AK. Evaluation of the Manchester classification system for chronic pancreatitis. JOP. 2006;7:390–6.

    PubMed  Google Scholar 

  84. Büchler MW, Martignoni ME, Friess H, Malfertheiner P. A proposal for a new clinical classification of chronic pancreatitis. BMC Gastroenterol. 2009;9:93.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Catalano MF, Sahai A, Levy M, Romagnuolo J, Wiersema M, Brugge W, Freeman M, Yamao K, Canto M, Hernandez LV. EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification. Gastrointest Endosc. 2009;69:1251–61.

    Article  PubMed  Google Scholar 

  86. Etemad B, Whitcomb DC. Chronic pancreatitis: diagnosis, classification, and new genetic developments. Gastroenterology. 2001;120:682–707.

    Article  CAS  PubMed  Google Scholar 

  87. Layer P, Melle U. Chronic pancreatitis: definition and classification for clinical practice. In: Dominguez-Munoz JE, editor. Clinical pancreatology for practising gastroenterologists and surgeons. Malden: Blackwell Publishing Ltd; 2005. p. 180–6.

    Google Scholar 

  88. Ramesh H. Proposal for a new grading system for chronic pancreatitis. The ABC system. J Clin Gastroenterol. 2002;35:67–70.

    Article  CAS  PubMed  Google Scholar 

  89. Whitcomb DC, Shimosegawa T, Chari ST, Forsmark CE, Frulloni L, Garg P, Hegyi P, Hirooka Y, Irisawa A, Ishikawa T, Isaji S, Lerch MM, Levy P, Masamune A, Wilcox CM, Windsor J, Yadav D, Sheel A, Neoptolemos JP. Working Group for the International Consensus Guidelines for Chronic P. International consensus statements on early chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with The International Association of Pancreatology, American Pancreatic Association, Japan Pancreas Society, PancreasFest Working Group and European Pancreatic Club. Pancreatology. 2018;18(5):516–27.

    Article  PubMed  Google Scholar 

  90. Lowenfels AB, Maisonneuve P, Whitcomb DC. Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group. Med Clin N Am. 2000;84:565–73.

    Article  CAS  PubMed  Google Scholar 

  91. Pfützer RH, Schneider A. Treatment of alcoholic pancreatitis. Dig Dis. 2005;23:241–6.

    Article  PubMed  Google Scholar 

  92. Shimosegawa T, Chari ST, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M, Kim MH, Kloppel G, Lerch MM, Lohr M, Notohara K, Okazaki K, Schneider A, Zhang L. International Association of P: International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011;40:352–8.

    Article  PubMed  Google Scholar 

  93. Talamini G, Bassi C, Falconi M, Frulloni L, Di Francesco V, Vaona B, Bovo P, Rigo L, Castagnini A, Angelini G, Vantini I, Pederzoli P, Cavallini G. Cigarette smoking: an independent risk factor in alcoholic pancreatitis. Pancreas. 1996;12:131–7.

    Article  CAS  PubMed  Google Scholar 

  94. Pungpapong S, Wallace MB, Woodward TA, Noh KW, Raimondo M. Accuracy of endoscopic ultrasonography and magnetic resonance cholangiopancreatography for the diagnosis of chronic pancreatitis. J Clin Gastroenterol. 2007;41:88–93.

    Article  PubMed  Google Scholar 

  95. Sheel ARG, Baron RD, Sarantitis I, Ramesh J, Ghaneh P, Raraty MGT, Yip V, Sutton R, Goulden MR, Campbell F, Farooq A, Healey P, Jackson R, Halloran CM, Neoptolemos JP. The diagnostic value of Rosemont and Japanese diagnostic criteria for “indeterminate”, “suggestive”, “possible” and “early” chronic pancreatitis. Pancreatology. 2018;18:774–84.

    Article  PubMed  Google Scholar 

  96. Kadiyala V, Lee LS, Banks PA, Suleiman S, Paulo JA, Wang W, Rosenblum J, Sainani NI, Mortele K, Conwell DL. Cigarette smoking impairs pancreatic duct cell bicarbonate secretion. JOP. 2013;14:31–8.

    PubMed  PubMed Central  Google Scholar 

  97. Bouwense SA, Olesen SS, Drewes AM, Frokjaer JB, van Goor H, Wilder-Smith OH. Is altered central pain processing related to disease stage in chronic pancreatitis patients with pain? An exploratory study. PLoS ONE. 2013;8:e55460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Stigliano S, Waldthaler A, Martinez-Moneo E, Lionetto L, Robinson S, Malvik M, Hedstrom A, Kaczka A, Scholdei M, Haas S, Simmaco M, Delle Fave G, Lohr M, Simon P, Capurso G. Vitamins D and K as factors associated with osteopathy in chronic pancreatitis: a prospective multicentre study (P-BONE study). Clin Transl Gastroenterol. 2018;9:197.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Novovic S, Borch A, Werge M, Karran D, Gluud L, Schmidt PN, Hansen EF, Nojgaard C, Jensen AB, Jensen FK, Frokjaer JB, Hansen MB, Jorgensen LN, Drewes AM, Olesen SS. Characterisation of the fibroinflammatory process involved in progression from acute to chronic pancreatitis: study protocol for a multicentre, prospective cohort study. BMJ Open. 2019;9:e028999.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Madzak A, Olesen SS, Haldorsen IS, Drewes AM, Frokjaer JB. Secretin-stimulated MRI characterization of pancreatic morphology and function in patients with chronic pancreatitis. Pancreatology. 2017;17:228–36.

    Article  CAS  PubMed  Google Scholar 

  101. Rahman A, O’Connor DB, Gather F, Koscic S, Gilgan J, Mockler D, Bashir Y, Memba R, Duggan SN, Conlon KC. Clinical classification and severity scoring systems in chronic pancreatitis: a systematic review. Dig Surg. 2020;37:181–91.

    Article  PubMed  Google Scholar 

  102. Diaconu BL, Ciobanu L, Mocan T, Pfützer RH, Scăfaru MP, Acalovschi M, Singer MV, Schneider A. Investigation of the SPINK1 N34S mutation in alcoholic chronic pancreatitis in Romania: a clinical analysis based on the criteria of the M-ANNHEIM classification. J Gastrointestinal Liver Dis. 2009;18:1430–50.

    Google Scholar 

  103. Hirth M, Weiss C, Ruckert F, Pfutzer RH, Wilhelm TJ, Hetjens S, Hardt PD, Gubergrits N, Ebert MP, Schneider A. Clinical evaluation of the M-ANNHEIM classification: development of the M-ANNHEIM-Surgery-Score as a new tool to monitor patients with chronic pancreatitis. Z Gastroenterol. 2018;56:1481–90.

    Article  PubMed  Google Scholar 

  104. Hirth M, Vujasinovic M, Munch M, Weiss C, Lohr M, Ebert MP, Schneider A. Monitoring and predicting disease activity in autoimmune pancreatitis with the M-ANNHEIM-AiP-Activity-Score. Pancreatology. 2018;18:29–38.

    Article  CAS  PubMed  Google Scholar 

  105. Hirth M, Hartel N, Weiss C, Hardt P, Gubergrits N, Ebert MP, Schneider A. Clinical course of chronic pancreatitis in elderly patients. Digestion. 2019;100:152–9.

    Article  CAS  PubMed  Google Scholar 

  106. Buscher HC, Wilder-Smith OH, van Goor H. Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study. Eur J Pain. 2006;10:363–70.

    Article  PubMed  Google Scholar 

  107. Chauhan S, Forsmark CE. Pain management in chronic pancreatitis: a treatment algorithm. Best Pract Res Clin Gastroenterol. 2010;24:323–35.

    Article  PubMed  Google Scholar 

  108. Gardner TB, Adler DG, Forsmark CE, Sauer BG, Taylor JR, Whitcomb DC. ACG clinical guideline: chronic pancreatitis. Am J Gastroenterol. 2020;115:322–39.

    Article  PubMed  Google Scholar 

  109. Conwell DL, Lee LS, Yadav D, Longnecker DS, Miller FH, Mortele KJ, Levy MJ, Kwon R, Lieb JG, Stevens T, Toskes PP, Gardner TB, Gelrud A, Wu BU, Forsmark CE, Vege SS. American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014;43:1143–62.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Gastroenterology and Hepatology, Medical Center Bad Hersfeld-Rotenburg, Bad Hersfeld, Germany

    Alexander Schneider

  2. Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

    Alexander Schneider & Michael Hirth

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Schneider, A., Hirth, M. Pain Management in Chronic Pancreatitis: Summary of Clinical Practice, Current Challenges and Potential Contribution of the M-ANNHEIM Classification. Drugs 81, 533–546 (2021). https://doi.org/10.1007/s40265-021-01472-7

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