Abstract
Tramadol and morphine were compared fortreatment of severe chronic pancreatitis pain and theirinteraction with gut motor function. Oral tramadol ormorphine doses were titrated double-blinded andrandomized for five days in 25 patients and pain, sideeffects, bowel function, orocecal and colonic transit,anal resting pressure, and rectal distension thresholdswere measured. Pain intensities (mean ± SD, 0 = none, 100 = unbearable) before treatment andon day 4 were 75 ± 19 and 8 ± 13 withtramadol (P < 0.001), and 65 ± 21 and 5± 6 with morphine (P < 0.001). On day 4, 67%of patients with tramadol and 20% with morphine rated their analgesia asexcellent (P < 0.001) with mean respective doses of840 mg (range: 80-1920) and 238 mg (20-1125). Orocecaltransit was unchanged after five days of tramadol, but increased with morphine (P < 0.05). Morepatients had prolonged colonic transit times withmorphine by day 5 (P < 0.05). Rectal distensionthreshold pressures increased only with tramadol (P < 0.01). It is concluded tramadol and morphineare potent analgesics in severe chronic pancreatitispain when individually titrated. Tramadol interferedsignificantly less with gastrointestinal function and was more often rated as an excellent analgesicthan morphine.
Similar content being viewed by others
REFERENCES
Lankisch PG: Chronic pancreatitis. In Bockus Gastroenterology, Volume 4, 5th ed. WS Haubrich, F Schaffner, Berk JE (eds). Philadelphia, WB Saunders, 1995, pp 2930–2958
Adler G, Schmid RM: Chronic pancreatitis: still puzzling? Gastroenterology 112:1762–1765, 1997
Bornman PC, Marks IN, Girdwood AH, Clain JE, Narunsky L, Clain DJ, Wright JP: Is pancreatic duct obstruction or stricture a major cause of pain in calcific pancreatitis? Br J Surg 67:425–428, 1980
Reisine T, Pasternak P: Opioid analgesics and antagonists. In Goodman & Gilman' s The Pharmacological Basis of Therapeutics, 9th ed. JG Hardman, LE Limbird (eds). New York, McGraw-Hill, 1996, pp 521–556
Burks TF, Hirning LD, Galligan JJ, Davis TP: Motility effects of opioid peptides in dog intestine. Life Sci 31:2237–2240, 1982
Raffa RB, Friedrichs E, Reimann W, Shank RP, Codd EE, Vaught JL: Opioid and non-opioid components independently contribute to the mechanism of action of tramadol, an "atypical" opioid analgesic. J Pharmacol Exp Ther 260:275–285, 1992
Friedrichs E, Reimann W, Selve N: Contribution of both enantiomers to antinociception of the centrally acting analgesic tramadol. Naunyn-Schmiedeberg's Arch Pharmacol 346(suppl 1):R36, 1992
Wilder-Smith CH, Schimke J, Osterwalder B, Senn HJ: Oral tramadol, a m-opioid agonist and monoamine reuptakeblocker, and morphine for strong cancer-related pain. Ann Clin Oncol 5:141–146, 1994
Rauck RL, Ruoff GE, McMillan JI: Comparison of tramadol and ace taminophen with code ine for long-term pain management in elderly patients. Curr TherRes 55:1417–1431, 1994
Preston KL, Jasinski DR, Testa M: Abuse potential and pharmacological comparison of tramadol and morphine. Drug Alcohol Depend 27:7–17, 1991
Vickers MD, O'Flaherty D, Szekely SM, Read M, Yoshizumi J: Tramadol: Pain relief by an opioid without depression of respiration. Anaesthesia 47:291–296, 1992
Staritz M, Poralla T, Manns M, Meyer zum Büschenfelde KH: Effect of modern analge sic drugs (tramadol, pentazocine and buprenorphine) on the bile duct sphincter in man. Gut 27:567–569, 1986
Coelho JCU, Runkel N, Herfarth C, Senninger N, Messmer K: Effect of analgesic drugs on the electromyographic activity of the gastrointestinal tract and sphincter of Oddi and on biliary pressure. Ann Surg 204:53–58, 1986
Sarles H, Adler G, Dani R: The pancre atitis classification of Marseilles-Rome 1988. Scand J Gastroenterol 24:641–642, 1989
Benedetti C. Acute pain: A review of its e ffects and therapy with systemic opioids. In Advance s in Pain Research and Therapy, Volume 14. C Benedetti, CR Chapman, G Giron (eds). New York, Raven Press, 1990, pp 367–424
Wilder-Smith CH: Visce rocutaneous nociception and anorectal motor function: a prospective study in asymptomatic, healthy volunteers. Gastroenterology 108:A709, 1995
Wilder-Smith CH, Bettiga A: The analgesic tramadol has minimal effect on gastrointestinal motor function. Br J Clin Pharmacol 43:71–75, 1997
La Brooy SJ, Male PJ, Beavis AK, Misiewicz JJ: Assessment of the reproducibility of the lactulose H2-breath test as a measure of mouth to caecum transit time. Gut 24:893–896, 1983
Read NW, Miles CA, Fisher D, Holgate AM, Kime ND, Mitchell MA, Reeve AM, Roche TB, Walker M: Transit of a meal through the stomach, small intestine and the colon in normal subjects and its role in the pathogenesis of diarrhea. Gastroenterology 79:1276–1282, 1980
Metcalf AM, Phillips SM, Zinsmeister AR, MacCarty RL, Beart RW, Wolff BG: Simplified assessment of segmental colonic transit. Gastroenterology 92:40–47, 1987
Meier R, Beglinger C, Dederding JP, Meyer-Wyss B, Fumagalli M, Rowedder A, Turberg J, Brignoli R: Alters-und geschle chtsspe zifische Normwerte der Dickdarmtransitzeit bei Gesunden. Schweiz Med Wochenschr 122:940–943, 1992
Caslavska J, Hufschmid E, Theurillat R, Desiderio C, Wolfisberg H, Thormann W: Screening for hydroxylation and ace tylation polymorphisms in man via simultaneous analysis of urinary metabolites of mephenytoin, dextromethorphan and caffeine by capillary electrophore tic techniques. J Chromatogr B 656:219–231, 1994
Bertilsson L: Geographical and interracial differences in polymorphic drug oxidation. Current status of knowledge of cytochromes P-450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 29:192–209, 1995
Schmid B, Bircher J, Preisig R, Küpfer A: Polymorphic dextromethorphan metabolism: Co-segre gation of oxidative Odemethylation with debrisoquin hydroxylation. Clin Pharmacol Ther 38:618–624, 1985
Beger HG, Büchler MW. Surgical Management of Chronic pancre atitis. In WS Haubrich, F Schaffner, JE Berk (eds).Bockus Gastroenterology, Volume 4, 5th ed. Philadelphia, WB Saunders, 1995, pp 2959–2968
Andren-Sandberg Å: Pain relief in pancreatic disease. Br J Surg 84:1041–1042, 1997
Yaksh TL: Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing. Pharmacol Biochem Behav 22:845–858, 1985
Danzebrink RM, Gebhart GF: Evidence that spinal 5HT1, 5HT2 and 5HT3 receptor subtypes modulate re sponses to noxious colorectal distension in the rat. Brain Res 538:64–75, 1991
Monks R: Psychotropic drugs. In PD Wall, R Melzack (eds).Textbook of Pain, 3rd ed. Edinburgh, Churchill Livingstone, 1994, pp 963–989
Sunshine A: New clinical experience with tramadol. Drugs 47( suppl. 1):8–18, 1994
Plourde V, Lembo T, Shui Z, Parker J, Mertz H, Tache Y, Sytnik B, Mayer E: Effects of somatostatin analogue octreotide on rectal afferent nerves in humans. Am J Physiol 265:G742–G751, 1993
Whitehead WE, Delvaux M: Standardization of barostat procedures for testing smooth muscletone and sensory thresholds in the gastrointestinal tract. Dig Dis Sci 42:223–241, 1997
Wilder-Smith CH, Hufschmid E, Thormann W: The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolisers. Br J Clin Pharmacol 45:575–581, 1998
Vickers MD, Paravicini D: Comparison of tramadol with morphine for postoperative pain following abdominal surgery. Eur J Anaesth 12:265–271, 1995
Chabal C, Erjavec MK, Jacobson L, Mariano A, Chaney E: Prescription opiate abuse in chronic pain patients: Clinical criteria, incidence, and predictors. Clin J Pain 13:150–155, 1997
Portenoy R: Chronic opioid therapy for nonmalignant pain: from models to practice. Am Pain Soc J 3:285–288, 1992
Rights and permissions
About this article
Cite this article
Wilder-Smith, C.H., Hill, L., Osler, W. et al. Effect of Tramadol and Morphine on Pain and Gastrointestinal Motor Function in Patients with Chronic Pancreatitis. Dig Dis Sci 44, 1107–1116 (1999). https://doi.org/10.1023/A:1026607703352
Issue Date:
DOI: https://doi.org/10.1023/A:1026607703352