Skip to main content
Log in

An Open-Label Trial of Theophylline for Functional Chest Pain

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Visceral hypersensitivity may play a role in the pathogenesis of functional chest pain, although the underlying mechanism(s) is unknown. We investigated the effects of theophylline, an adenosine receptor antagonist, on sensory perception and biomechanical properties of esophagus in patients with functional chest pain. Esophageal balloon distention was performed using impedance planimetry in 21 consecutive patients with functional chest pain. Patients found to have a hypersensitive esophagus received intravenous theophylline and balloon distension was repeated. If the hypersensitivity improved, oral theophylline was prescribed for three months as an open label trial. Balloon distension reproduced typical chest pain in 16 (76%) patients at thresholds suggestive of hypersensitivity. After theophylline infusion, pain thresholds increased in 12 (75%) patients. Median threshold pressures for discomfort and pain improved (P < 0.01). Cross-sectional area increased (P < 0.05) and the tension/strain association shifted to the right (P < 0.01). Seven of eight patients reported sustained improvement in pain after oral theophylline. Theophylline may ameliorate chest pain in patients with hypersensitive esophagus, possibly by altering adenosine-mediated nociception.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Clouse RE, Richter JE, Heading RC, Jannssens J, Wilson JA: Functional esophageal disorders. In Rome II: The Functional Gastrointestinal Disorders. AD Drossman, E Corazziari, NJ Talley, WG Thompson, and WE Whitehead (eds). McLean, Virginia, Degnon Associates, 2000, pp 247–298

    Google Scholar 

  2. Ockene IS, Shay MJ, Alpert JS, Weiner BH, Dalen JE: Unexplained chest pain in patients with normal coronary arteriograms: a follow up study of functional status. N Engl J Med 303(22):1249–1252, 1980

    Google Scholar 

  3. Ward BW, Wu WC, Richter JE, Hackshaw BT, Castell DO: Long-term follow up of symptomatic status of patients with noncardiac chest pain; is diagnosis of esophageal etiology helpful? Am J Gastroenterol 82(3):215–218, 1987

    Google Scholar 

  4. Barish CF, Castell DO, Richter JE: Graded esophageal balloon distention: a new provocation for non-cardiac chest pain. Dig Dis Sci 31(12):1292–1298, 1986

    Google Scholar 

  5. Katz PO, Dalton CB, Richter JE, Wu WC, Castell DO: Esophageal testing in patients with non-cardiac chest pain or dysphagia-results of three years' experience with 1161 patients. Ann Int Med 106(4):593–597, 1987

    Google Scholar 

  6. Richter JE, Barish CF, Castell DO: Abnormal Sensory perception in patients with esophageal chest pain. Gastroenterology 91(4):845–852, 1986

    Google Scholar 

  7. Deschner WK, Maher KA, Calttau L Jr, Benjamin SB: Intraesophageal balloon distention vs drug provocation in the evaluation of non-cardiac chest pain. Am J Gastroenterol 85(8):938–943, 1990

    Google Scholar 

  8. Rao SSC, Gregersen H, Hayek B, Summers RW, Christensen J: Unexplained chest pain: The hypersensitive, hyperreactive and poorly compliant esophagus. Ann Intern Med 124(11):950–958, 1996

    Google Scholar 

  9. Cervero F, Janig W: Visceral nociceptors: a new world order? Trends Neurosci. 15(10):374–378, 1992

    Google Scholar 

  10. Mayer EA, Gebhart GF: Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 107(1):271–293, 1994

    Google Scholar 

  11. Sarkar S, Aziz Q, Woolf CJ, Hobson AR, Thompson DG: Contribution of central sensitisation to the development of non-cardiac chest pain. Lancet 356(9236):1154–1159, 2000

    Google Scholar 

  12. Varaia I, Logue E, O'Connor C, Newby K, Wagner HR, Davenport C, et al: Randomized trial of sertraline in patients with unexplained chest pain of noncardiac origin. Am Heart J 140(3):367–372, 2000

    Google Scholar 

  13. Sawynok J: Adenosine receptor activation and nociception. Eur J Pharmacol 347(1):1–11, 1998

    Google Scholar 

  14. Bueno L, Fioramanti J, Delvaux M, Frexinos J: Mediators and pharmacology of visceral sensitivity: from basic to clinical investigations. Gastroenterology 112(5):1714–1743, 1997

    Google Scholar 

  15. Sylven C, Beerman B, Jonzon B, Brandt R: Angina pectoris like pain provoked by intravenous adenosine in healthy volunteers. BMJ 293(6541):227–230, 1986

    Google Scholar 

  16. Crea F, Pupita G, Galassi AR, el-Tamimi H, Kaski JC, Davies G, et al: Role of adenosine in pathogenesis of anginal pain. Circulation 81(1):164–172, 1990

    Google Scholar 

  17. Gaspardone A, Crea F, Tomai F, Versaci F, Iamele M, Gioffre G, et al: Muscular and cardiac adenosine-induced pain is mediated by A1 receptors. J Am Coll Cardiol 25(1):251–257, 1995

    Google Scholar 

  18. Bleehen T, Keele CA: Observation on the algogenic actions of adenosine compounds on the human blister base preparation. Pain 3(4):367–377, 1997

    Google Scholar 

  19. Taiwo YO, Levine JD: Direct cutaneous hyperalgesia induced by adenosine. Neuroscience 38(3):756–762, 1990

    Google Scholar 

  20. Pappagallo M, Gaspardone A, Tomai F, Iamele M, Crea F, Gioffre PA: Analgesic effect of bamiphylline on pain induced by intradermal injection of adenosine. Pain 53(2):199–204, 1993

    Google Scholar 

  21. Sawynok J, Yaksh TL: Caffeine as an analgesic adjuvant: a review of pharmacology and mechanism of action. Pharmacol Rev 45(1):43–85, 1993

    Google Scholar 

  22. Minton NA, Henry JA: Pharmacodynamic interaction between infused adenosine and oral theophylline. Hum Exp Toxicol 10(6):411–418, 1991

    Google Scholar 

  23. Rao SSC, Hayek B, Summers RW: Impedance planimetry: an integrated approach for assessing sensory, active and passive biomechanical properties of the esophagus. Am J Gastroenterol 90(3):431–438, 1995

    Google Scholar 

  24. Patel RS, Rao SSC: Biomechanical and sensory parameters of the esophagus at four levels. Am J Physiol 275(2 Pt 1):G187–G191, 1998

    Google Scholar 

  25. Gregersen H, Djurhuus JC: Impedance planimetry: A new approach to biomechanical intestinal wall properties. Dig Dis Sci 9(6):332–340, 1991

    Google Scholar 

  26. Mujica V, Mudipalli VR, Rao SSC: Pathophysiology of chest pain in patients with nutcracker esophagus. Am J Gastroenterol 2001 (in press)

  27. Orvar K, Gregersen H, Christensen J: Biomechanical characteristics of the human esophagus. Dig Dis Sci 38(2):197–205, 1993

    Google Scholar 

  28. Offma, JJ, Gralnek IM, Udani J, Fennerty MB, Fass R: The cost-effectiveness of omeprazole tests in patients with noncardiac chest pain. Am J Med 17(3):219–227, 1999

    Google Scholar 

  29. Achem SR, DeVault KR: Unexplained chest pain at the turn of the century. Am J Gastroenterol 94(1):5–8, 1999

    Google Scholar 

  30. Fass R, Fennerty MB, Johnson C, Camargo L, Sampliner RE: Correlation of ambulatory 24-hour esophageal pH monitoring results with symptom improvement in patients with noncardiac chest pain due to gastroesophageal reflux disease. J Clin Gastroenterol 28(1):36–39, 1999

    Google Scholar 

  31. Cannon RO 3rd, Quyyumi AA, Mincemoyer R, Stine AM, Gracely RH, Smith WB, et al: Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med 330(20):1411–1417, 1994

    Google Scholar 

  32. Clouse RE, Lustman PJ, Eckert TC, Ferney DM, Griffith LS: Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities. A double-blind, placebo-controlled trial. Gastroenterology. 92(4):1027–1036, 1987

    Google Scholar 

  33. Rao SSC, Hayek, Summers RW: Unexplained chest pain: Esophageal hypersensitivity or motor dysfunction? Am J Gastroenterol 96(8):2584–2589, 2001

    Google Scholar 

  34. Richter JE, Dalton CB, Buice RG, Castell DO: Nifedepine: a potent inhibitor of contractions in the body of human esophagus: studies in healthy volunteers and patients with Nutcracker esophagus. Dig Dis Sci 89(3):549–554, 1985

    Google Scholar 

  35. Bertrand C, Nadel JA, Yamawaki I, Geppetti P: Role of kinins in the vascular extravasation evoked by antigen and mediated by tachykinins in guinea pig trachea. J Immunol 151(9):4902–4907, 1993

    Google Scholar 

  36. Julia V, Su X, Bueno L, Gebhart GF: Role of neurokinin 3 receptors on responses to colorectal distention in the rat: electrophysiological and behavioral studies. Gastroenterology 116(5):1124–1131, 1999

    Google Scholar 

  37. Krysiak PS, Preiksaitis HG: Tachykinins contribute to nerve mediated contractions in human esophagus. Gastroenterology 120:39–48, 2001

    Google Scholar 

  38. Ploudre V, St-Pierre S, Quirion R: Calcitonin gene-related peptide in viscerosensitive response to colorectal distension in rats. Am J Physiol 273(1 Pt 1):G191–G196, 1997

    Google Scholar 

  39. Edlund A, Conradsson T, Sollevi A: A role for adenosine in coronary vasoregulation in man. Effects of theophylline and enprofylline. Clin Physiol 15(6):623–636, 1995

    Google Scholar 

  40. Lanza GA, Gaspardone A, Pasceri V, Perino M, Colonna G, Tomai F, et al: Effects of bamiphylline on exercise testing in patients with syndrome X. G Ital Cardiol 27(1):50–54, 1997

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rao, S.S., Mudipalli, R.S., Mujica, V. et al. An Open-Label Trial of Theophylline for Functional Chest Pain. Dig Dis Sci 47, 2763–2768 (2002). https://doi.org/10.1023/A:1021017524660

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021017524660

Navigation