Pain and chronic pancreatitis: A complex interplay of multiple mechanisms

World Journal of Gastroenterology

Volumn 19, Issue 42, 2013, Pages 7282-7291

  Poulsen, Jakob Lykke ^a   Olesen, Søren Schou ^a   Malver, Lasse Paludan ^a   Frøkjær, Jens Brøndum ^b   Drewes, Asbjørn Mohr ^a  

^a AALBORG UNIVERSITY HOSPITAL   (Denmark)

^b AALBORG UNIVERSITY   (Denmark)

Author keywords

Abdominal pain; Chronic pancreatitis; Neuropathy; Pain mechanisms; Sensitization

Indexed keywords

CHOLECYSTOKININ; CHOLECYSTOKININ A RECEPTOR ANTAGONIST; OPIATE; PLACEBO;

ABDOMINAL PAIN; ANALGESIA; CHOLESTASIS; CHRONIC PANCREATITIS; CONSTIPATION; CONTROLLED CLINICAL TRIAL (TOPIC); GASTROINTESTINAL REFLUX; HUMAN; MULTICENTER STUDY (TOPIC); NAUSEA; PAIN GENERATION; PAIN MECHANISM; PAIN THRESHOLD; PANCREAS DISEASE; PANCREAS PSEUDOCYST; PANCREATIC DUCT HYPERTENSION; PANCREATIC NEUROPATHY; PANCREATIC PARENCHYMAL HYPERTENSION; PATHOGENESIS; PEPTIC ULCER; PLUMBING; REVIEW; SPLEEN VEIN THROMBOSIS; WIRING;

ABDOMINAL PAIN; CHRONIC PANCREATITIS; NEUROPATHY; PAIN MECHANISMS; SENSITIZATION;

ABDOMINAL PAIN; ANIMALS; HUMANS; PAIN MANAGEMENT; PAIN MEASUREMENT; PAIN PERCEPTION; PAIN THRESHOLD; PANCREAS; PANCREATITIS, CHRONIC; RISK FACTORS; TREATMENT OUTCOME; VISCERAL AFFERENTS;

EID: 84887570907     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v19.i42.7282     Document Type: Review

References (87)

1. Pasricha PJ. Unraveling the mystery of pain in chronic pancreatitis. Nat Rev Gastroenterol Hepatol 2012; 9: 140-151 [PMID: 22269952 DOI: 10.1038/nrgastro.2011.274]
2. Fasanella KE, Davis B, Lyons J, Chen Z, Lee KK, Slivka A, Whitcomb DC. Pain in chronic pancreatitis and pancreatic cancer. Gastroenterol Clin North Am 2007; 36: 335-64.ix [PMID: 17533083 DOI: 10.1016/j.gtc.2007.03.011]
3. Ammann RW, Muellhaupt B. The natural history of pain in alcoholic chronic pancreatitis. Gastroenterology 1999; 116: 1132-1140 [PMID: 10220505]
4. Ammann RW, Buehler H, Muench R, Freiburghaus AW, Siegenthaler W. Differences in the natural history of idiopathic (nonalcoholic) and alcoholic chronic pancreatitis. A comparative long-term study of 287 patients. Pancreas 1987; 2: 368-377 [PMID: 3628234]
5. Lankisch PG, Löhr-Happe A, Otto J, Creutzfeldt W. Natural course in chronic pancreatitis. Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease. Digestion 1993; 54: 148-155 [PMID: 8359556]
6. 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. 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 [PMID: 21148579 DOI: 10.1136/gut.2010.213835]
7. Amann ST, Yadav D, Barmada MM, O'Connell M, Kennard ED, Anderson M, Baillie J, Sherman S, Romagnuolo J, Hawes RH, Alkaade S, Brand RE, Lewis MD, Gardner TB, Gelrud A, Money ME, Banks PA, Slivka A, Whitcomb DC. Physical and mental quality of life in chronic pancreatitis: a case-control study from the North American Pancreatitis Study 2 cohort. Pancreas 2013; 42: 293-300 [PMID: 23357924 DOI: 10.1097/MPA.0b013e31826532e7]
8. 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 [PMID: 20118821 DOI: 10.1097/MPA.0b013e3181c5c693]
9. Drewes AM, Krarup AL, Detlefsen S, Malmstrøm ML, Dimcevski G, Funch-Jensen P. Pain in chronic pancreatitis: the role of neuropathic pain mechanisms. Gut 2008; 57: 1616-1627 [PMID: 18566105 DOI: 10.1136/gut.2007.146621]
10. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med 2004; 140: 441-451 [PMID: 15023710]
11. Lieb JG, Forsmark CE. Review article: pain and chronic pancreatitis. Aliment Pharmacol Ther 2009; 29: 706-719 [PMID: 19284407 DOI: 10.1111/j.1365-2036.2009.03931.x]
12. Anaparthy R, Pasricha PJ. Pain and chronic pancreatitis: is it the plumbing or the wiring? Curr Gastroenterol Rep 2008; 10: 101-106 [PMID: 18462594]
13. White TT, Bourde J. A new observation on human intraductal pancreatic pressure. Surg Gynecol Obstet 1970; 130: 275-278 [PMID: 4983472]
14. Sato T, Miyashita E, Yamauchi H, Matsuno S. The role of surgical treatment for chronic pancreatitis. Ann Surg 1986; 203: 266-271 [PMID: 2420294]
15. Okazaki K, Yamamoto Y, Ito K. Endoscopic measurement of papillary sphincter zone and pancreatic main ductal pressure in patients with chronic pancreatitis. Gastroenterology 1986; 91: 409-418 [PMID: 3721126]
16. Laugier R. Dynamic endoscopic manometry of the response to secretin in patients with chronic pancreatitis. Endoscopy 1994; 26: 222-227 [PMID: 8026369 DOI: 10.1055/ s-2007-1008947]
17. Novis BH, Bornman PC, Girdwood AW, Marks IN. Endoscopic manometry of the pancreatic duct and sphincter zone in patients with chronic pancreatitis. Dig Dis Sci 1985; 30: 225-228 [PMID: 3971834]
18. Rolny P, Arlebäck A, Järnerot G, Andersson T. Endoscopic manometry of the sphincter of Oddi and pancreatic duct in chronic pancreatitis. Scand J Gastroenterol 1986; 21: 415-420 [PMID: 3726450]
19. Ugljesić M, Bulajić M, Milosavljević T, Stimec B. Endoscopic manometry of the sphincter of Oddi and pancreatic duct in patients with chronic pancreatitis. Int J Pancreatol 1996; 19: 191-195 [PMID: 8807364 DOI: 10.1007/ BF02787367]
20. Vestergaard H, Kruse A, Rokkjaer M, Frøbert O, Thommesen P, Funch-Jensen P. Endoscopic manometry of the sphincter of Oddi and the pancreatic and biliary ducts in patients with chronic pancreatitis. Scand J Gastroenterol 1994; 29: 188-192 [PMID: 8171290]
21. Ebbehøj N, Svendsen LB, Madsen P. Pancreatic tissue pressure: techniques and pathophysiological aspects. Scand J Gastroenterol 1984; 19: 1066-1068 [PMID: 6533777]
22. Ebbehøj N, Borly L, Madsen P, Svendsen LB. Pancreatic tissue pressure and pain in chronic pancreatitis. Pancreas 1986; 1: 556-558 [PMID: 3562446]
23. Ebbehøj N, Borly L, Bülow J, Rasmussen SG, Madsen P. Evaluation of pancreatic tissue fluid pressure and pain in chronic pancreatitis. A longitudinal study. Scand J Gastroenterol 1990; 25: 462-466 [PMID: 2359973]
24. Manes G, Büchler M, Pieramico O, Di Sebastiano P, Malfertheiner P. Is increased pancreatic pressure related to pain in chronic pancreatitis? Int J Pancreatol 1994; 15: 113-117 [PMID: 8071569]
25. Patel AG, Toyama MT, Alvarez C, Nguyen TN, Reber PU, Ashley SW, Reber HA. Pancreatic interstitial pH in human and feline chronic pancreatitis. Gastroenterology 1995; 109: 1639-1645 [PMID: 7557149]
26. Zhu Y, Colak T, Shenoy M, Liu L, Pai R, Li C, Mehta K, Pasricha PJ. Nerve growth factor modulates TRPV1 expression and function and mediates pain in chronic pancreatitis. Gastroenterology 2011; 141: 370-377 [PMID: 21473865 DOI: 10.1053/j.gastro.2011.03.046]
27. Schwartz ES, La JH, Scheff NN, Davis BM, Albers KM, Gebhart GF. TRPV1 and TRPA1 antagonists prevent the transition of acute to chronic inflammation and pain in chronic pancreatitis. J Neurosci 2013; 33: 5603-5611 [PMID: 23536075 DOI: 10.1523/JNEUROSCI.1806-12.2013]
28. Warshaw AL, Banks PA, Fernández-Del Castillo C. AGA technical review: treatment of pain in chronic pancreatitis. Gastroenterology 1998; 115: 765-776 [PMID: 9721175]
29. Andrén-Sandberg A, Hoem D, Gislason H. Pain management in chronic pancreatitis. Eur J Gastroenterol Hepatol 2002; 14: 957-970 [PMID: 12352215]
30. Frøkjær JB, Olesen SS, Drewes AM. Fibrosis, atrophy, and ductal pathology in chronic pancreatitis are associated with pancreatic function but independent of symptoms. Pancreas 2013; 42: 1182-1187 [PMID: 24048457]
31. Balci NC, Perman WH, Saglam S, Akisik F, Fattahi R, Bilgin M. Diffusion-weighted magnetic resonance imaging of the pancreas. Top Magn Reson Imaging 2009; 20: 43-47 [PMID: 19687725 DOI: 10.1097/RMR.0b013e3181b48667]
32. Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008; 70: 1630-1635 [PMID: 18003941 DOI: 10.1212/01.wnl.0000282763.29778.59]
33. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature 2001; 413: 203-210 [PMID: 11557989 DOI: 10.1038/35093019]
34. Xu GY, Winston JH, Shenoy M, Yin H, Pendyala S, Pasricha PJ. Transient receptor potential vanilloid 1 mediates hyperalgesia and is up-regulated in rats with chronic pancreatitis. Gastroenterology 2007; 133: 1282-1292 [PMID: 17698068 DOI: 10.1053/j.gastro.2007.06.015]
35. Hartel M, di Mola FF, Selvaggi F, Mascetta G, Wente MN, Felix K, Giese NA, Hinz U, Di Sebastiano P, Büchler MW, Friess H. Vanilloids in pancreatic cancer: potential for chemotherapy and pain management. Gut 2006; 55: 519-528 [PMID: 16174661 DOI: 10.1136/gut.2005.073205]
36. Friess H, Zhu ZW, di Mola FF, Kulli C, Graber HU, Andren- Sandberg A, Zimmermann A, Korc M, Reinshagen M, Büchler MW. Nerve growth factor and its high-affinity receptor in chronic pancreatitis. Ann Surg 1999; 230: 615-624 [PMID: 10561084]
37. Zhu ZW, Friess H, Wang L, Zimmermann A, Büchler MW. Brain-derived neurotrophic factor (BDNF) is upregulated and associated with pain in chronic pancreatitis. Dig Dis Sci 2001; 46: 1633-1639 [PMID: 11508661]
38. Gebhart GF. Visceral pain-peripheral sensitisation. Gut 2000; 47 Suppl 4: iv54-iv5. discussion iv58 [PMID: 11076915]
39. Anand P, Aziz Q, Willert R, van Oudenhove L. Peripheral and central mechanisms of visceral sensitization in man. Neurogastroenterol Motil 2007; 19: 29-46 [PMID: 17280584 DOI: 10.1111/j.1365-2982.2006.00873.x]
40. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science 2000; 288: 1765-1769 [PMID: 10846153]
41. Bockman DE, Buchler M, Malfertheiner P, Beger HG. Analysis of nerves in chronic pancreatitis. Gastroenterology 1988; 94: 1459-1469 [PMID: 3360267]
42. Keith RG, Keshavjee SH, Kerenyi NR. Neuropathology of chronic pancreatitis in humans. Can J Surg 1985; 28: 207-211 [PMID: 3995416]
43. Ceyhan GO, Demir IE, Rauch U, Bergmann F, Müller MW, Büchler MW, Friess H, Schäfer KH. Pancreatic neuropathy results in "neural remodeling" and altered pancreatic innervation in chronic pancreatitis and pancreatic cancer. Am J Gastroenterol 2009; 104: 2555-2565 [PMID: 19568227 DOI: 10.1038/ajg.2009.380]
44. Ceyhan GO, Bergmann F, Kadihasanoglu M, Altintas B, Demir IE, Hinz U, Müller MW, Giese T, Büchler MW, Giese NA, Friess H. Pancreatic neuropathy and neuropathic pain- -a comprehensive pathomorphological study of 546 cases. Gastroenterology 2009; 136: 177-186.e1 [PMID: 18992743 DOI: 10.1053/j.gastro.2008.09.029]
45. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011; 152: S2-15 [PMID: 20961685 DOI: 10.1016/j.pain.2010.09.030]
46. Kuner R. Central mechanisms of pathological pain. Nat Med 2010; 16: 1258-1266 [PMID: 20948531 DOI: 10.1038/nm.2231]
47. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009; 10: 895-926 [PMID: 19712899 DOI: 10.1016/ j.jpain.2009.06.012]
48. Arendt-Nielsen L, Laursen RJ, Drewes AM. Referred pain as an indicator for neural plasticity. Prog Brain Res 2000; 129: 343-356 [PMID: 11098702]
49. Drewes AM, Pedersen J, Liu W, Arendt-Nielsen L, Gregersen H. Controlled mechanical distension of the human oesophagus: sensory and biomechanical findings. Scand J Gastroenterol 2003; 38: 27-35 [PMID: 12608461]
50. Dimcevski G, Sami SA, Funch-Jensen P, Le Pera D, Valeriani M, Arendt-Nielsen L, Drewes AM. Pain in chronic pancreatitis: the role of reorganization in the central nervous system. Gastroenterology 2007; 132: 1546-1556 [PMID: 17408654 DOI: 10.1053/j.gastro.2007.01.037]
51. Buscher HC, Wilder-Smith OH, van Goor H. Chronic pancreatitis patients show hyperalgesia of central origin: a pilot study. Eur J Pain 2006; 10: 363-370 [PMID: 16087373 DOI: 10.1016/j.ejpain.2005.06.006]
52. Olesen SS, Brock C, Krarup AL, Funch-Jensen P, Arendt- Nielsen L, Wilder-Smith OH, Drewes AM. Descending inhibitory pain modulation is impaired in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2010; 8: 724-730 [PMID: 20304100 DOI: 10.1016/j.cgh.2010.03.005]
53. Olesen SS, Frøkjær JB, Lelic D, Valeriani M, Drewes AM. Pain-associated adaptive cortical reorganisation in chronic pancreatitis. Pancreatology 2010; 10: 742-751 [PMID: 21273802 DOI: 10.1159/000321644]
54. Olesen SS, Hansen TM, Graversen C, Steimle K, Wilder- Smith OH, Drewes AM. Slowed EEG rhythmicity in patients with chronic pancreatitis: evidence of abnormal cerebral pain processing? Eur J Gastroenterol Hepatol 2011; 23: 418-424 [PMID: 21399506 DOI: 10.1097/MEG.0b013e3283457b09]
55. Olesen SS, Hansen TM, Graversen C, Valeriani M, Drewes AM. Cerebral excitability is abnormal in patients with painful chronic pancreatitis. Eur J Pain 2013; 17: 46-54 [PMID: 22508470 DOI: 10.1002/j.1532-2149.2012.00155.x]
56. Frøkjær JB, Andersen LW, Brock C, Simrén M, Ljungberg M, Søfteland E, Dimcevski G, Yavarian Y, Gregersen H, Drewes AM. Altered brain microstructure assessed by diffusion tensor imaging in patients with diabetes and gastrointestinal symptoms. Diabetes Care 2013; 36: 662-668 [PMID: 23139372 DOI: 10.2337/dc12-1131]
57. Frøkjær JB, Bouwense SA, Olesen SS, Lundager FH, Eskildsen SF, van Goor H, Wilder-Smith OH, Drewes AM. Reduced cortical thickness of brain areas involved in pain processing in patients with chronic pancreatitis. Clin Gastroenterol Hepatol 2012; 10: 434-8.e1 [PMID: 22155560 DOI: 10.1016/j.cgh.2011.11.024]
58. Bouwense SA, Olesen SS, Drewes AM, Frøkjær 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 [PMID: 23405154 DOI: 10.1371/journal.pone.0055460]
59. Vera-Portocarrero LP, Xie JY, Kowal J, Ossipov MH, King T, Porreca F. Descending facilitation from the rostral ventromedial medulla maintains visceral pain in rats with experimental pancreatitis. Gastroenterology 2006; 130: 2155-2164 [PMID: 16762636 DOI: 10.1053/j.gastro.2006.03.025]
60. 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: 531-536 [PMID: 22005656 DOI: 10.1097/AAP.0b013e31822e0d4a]
61. Boerma D, Obertop H, Gouma DJ. Pancreatic pseudocysts in chronic pancreatitis. Surgical or interventional drainage? Ann Ital Chir 2000; 71: 43-50 [PMID: 10829523]
62. Andrén-Sandberg A, Dervenis C. Pancreatic pseudocysts in the 21st century. Part I: classification, pathophysiology, anatomic considerations and treatment. JOP 2004; 5: 8-24 [PMID: 14730118]
63. 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: 820-828 [PMID: 6706066]
64. Aghdassi A, Mayerle J, Kraft M, Sielenkämper AW, Heidecke CD, Lerch MM. Diagnosis and treatment of pancreatic pseudocysts in chronic pancreatitis. Pancreas 2008; 36: 105-112 [PMID: 18376299 DOI: 10.1097/ MPA.0b013e31815a8887]
65. Gouyon B, Lévy P, Ruszniewski P, Zins M, Hammel P, Vilgrain V, Sauvanet A, Belghiti J, Bernades P. Predictive factors in the outcome of pseudocysts complicating alcoholic chronic pancreatitis. Gut 1997; 41: 821-825 [PMID: 9462217]
66. Vijungco JD, Prinz RA. Management of biliary and duodenal complications of chronic pancreatitis. World J Surg 2003; 27: 1258-1270 [PMID: 14534824 DOI: 10.1007/ s00268-003-7246-7]
67. Abdallah AA, Krige JE, Bornman PC. Biliary tract obstruction in chronic pancreatitis. HPB (Oxford) 2007; 9: 421-428 [PMID: 18345288 DOI: 10.1080/13651820701774883]
68. Kalvaria I, Bornman PC, Marks IN, Girdwood AH, Bank L, Kottler RE. The spectrum and natural history of common bile duct stenosis in chronic alcohol-induced pancreatitis. Ann Surg 1989; 210: 608-613 [PMID: 2818030]
69. Prinz RA, Aranha GV, Greenlee HB. Combined pancreatic duct and upper gastrointestinal and biliary tract drainage in chronic pancreatitis. Arch Surg 1985; 120: 361-366 [PMID: 3970672]
70. Kahl S, Zimmermann S, Genz I, Schmidt U, Pross M, Schulz HU, Malfertheiner P. Biliary strictures are not the cause of pain in patients with chronic pancreatitis. Pancreas 2004; 28: 387-390 [PMID: 15097855]
71. Chebli JM, de Souza AF, Gaburri PD, Bastos KV, Ribeiro TC, Filho RJ, Chebli LA, Castro Ferreira LE. Prevalence and pathogenesis of duodenal ulcer in chronic alcoholic pancreatitis. J Clin Gastroenterol 2002; 35: 71-74 [PMID: 12080230]
72. Schulze S, Thorsgaard Pedersen N, Jørgensen MJ, Møllmann KM, Rune SJ. Association between duodenal bulb ulceration and reduced exocrine pancreatic function. Gut 1983; 24: 781-783 [PMID: 6884816]
73. Saunders JH, Cargill JM, Wormsley KG. Gastric secretion of acid in patients with pancreatic disease. Digestion 1978; 17: 365-369 [PMID: 669079]
74. Piubello W, Vantini I, Scuro LA, Novelli P, Benini L, Brocco G, Cavallini G. Gastric secretion, gastroduodenal histological changes, and serum gastrin in chronic alcoholic pancreatitis. Am J Gastroenterol 1982; 77: 105-110 [PMID: 7072677]
75. Weber SM, Rikkers LF. Splenic vein thrombosis and gastrointestinal bleeding in chronic pancreatitis. World J Surg 2003; 27: 1271-1274 [PMID: 14502405 DOI: 10.1007/ s00268-003-7247-6]
76. ROSCH J, HERFORT K. Contribution of splenoportography to the diagnosis of diseases of the pancreas. II. Inflammatory diseases. Acta Med Scand 1962; 171: 263-272 [PMID: 14493804]
77. Rignault D, Mine J, Moine D. Splenoportographic changes in chronic pancreatitis. Surgery 1968; 63: 571-575 [PMID: 5689513]
78. Bernades P, Baetz A, Lévy P, Belghiti J, Menu Y, Fékété F. Splenic and portal venous obstruction in chronic pancreatitis. A prospective longitudinal study of a medical-surgical series of 266 patients. Dig Dis Sci 1992; 37: 340-346 [PMID: 1735356]
79. Brock C, Olesen SS, Olesen AE, Frøkjaer JB, Andresen T, Drewes AM. Opioid-induced bowel dysfunction: pathophysiology and management. Drugs 2012; 72: 1847-1865 [PMID: 22950533 DOI: 10.2165/11634970-000000000-00000]
80. Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioidinduced bowel disorders and narcotic bowel syndrome in patients with chronic non-cancer pain. Neurogastroenterol Motil 2010; 22: 424-30, e96 [PMID: 20100280 DOI: 10.1111/ j.1365-2982.2009.01458.x]
81. Casellas F, Guarner L, Vaquero E, Antolín M, de Gracia X, Malagelada JR. Hydrogen breath test with glucose in exocrine pancreatic insufficiency. Pancreas 1998; 16: 481-486 [PMID: 9598808]
82. Garcés MC, Gómez-Cerezo J, Alba D, Codoceo R, Vázquez- Muñoz E, Arnalich F, Barbado FJ, Vázquez JJ. Relationship of basal and postprandial intraduodenal bile acid concentrations and plasma cholecystokinin levels with abdominal pain in patients with chronic pancreatitis. Pancreas 1998; 17: 397-401 [PMID: 9821182]
83. Xie JY, Herman DS, Stiller CO, Gardell LR, Ossipov MH, Lai J, Porreca F, Vanderah TW. Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. J Neurosci 2005; 25: 409-416 [PMID: 15647484 DOI: 10.1523/JNEUROSCI.4054-04.2005]
84. Shiratori K, Takeuchi T, Satake K, Matsuno S. Clinical evaluation of oral administration of a cholecystokinin-A receptor antagonist (loxiglumide) to patients with acute, painful attacks of chronic pancreatitis: a multicenter dose-response study in Japan. Pancreas 2002; 25: e1-e5 [PMID: 12131781]
85. Buscher HC, van Goor H, Sweep CG, Lenders JW, Wilder-Smith OH. Increased sympathetic activity in chronic pancreatitis patients is associated with hyperalgesia. J Pain Palliat Care Pharmacother 2010; 24: 362-366 [PMID: 21133744 DOI: 10.3109/15360288.2010.519762]
86. Chandrasekharan B, Srinivasan S. Diabetes and the enteric nervous system. Neurogastroenterol Motil 2007; 19: 951-960 [PMID: 17971027 DOI: 10.1111/j.1365-2982.2007.01023.x]
87. Demir IE, Tieftrunk E, Maak M, Friess H, Ceyhan GO. Pain mechanisms in chronic pancreatitis: of a master and his fire. Langenbecks Arch Surg 2011; 396: 151-160 [PMID: 21153480 DOI: 10.1007/s00423-010-0731-1]