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.
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REFERENCES
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
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
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
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
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
Richter JE, Barish CF, Castell DO: Abnormal Sensory perception in patients with esophageal chest pain. Gastroenterology 91(4):845–852, 1986
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
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
Cervero F, Janig W: Visceral nociceptors: a new world order? Trends Neurosci. 15(10):374–378, 1992
Mayer EA, Gebhart GF: Basic and clinical aspects of visceral hyperalgesia. Gastroenterology 107(1):271–293, 1994
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
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
Sawynok J: Adenosine receptor activation and nociception. Eur J Pharmacol 347(1):1–11, 1998
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
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
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
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
Bleehen T, Keele CA: Observation on the algogenic actions of adenosine compounds on the human blister base preparation. Pain 3(4):367–377, 1997
Taiwo YO, Levine JD: Direct cutaneous hyperalgesia induced by adenosine. Neuroscience 38(3):756–762, 1990
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
Sawynok J, Yaksh TL: Caffeine as an analgesic adjuvant: a review of pharmacology and mechanism of action. Pharmacol Rev 45(1):43–85, 1993
Minton NA, Henry JA: Pharmacodynamic interaction between infused adenosine and oral theophylline. Hum Exp Toxicol 10(6):411–418, 1991
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
Patel RS, Rao SSC: Biomechanical and sensory parameters of the esophagus at four levels. Am J Physiol 275(2 Pt 1):G187–G191, 1998
Gregersen H, Djurhuus JC: Impedance planimetry: A new approach to biomechanical intestinal wall properties. Dig Dis Sci 9(6):332–340, 1991
Mujica V, Mudipalli VR, Rao SSC: Pathophysiology of chest pain in patients with nutcracker esophagus. Am J Gastroenterol 2001 (in press)
Orvar K, Gregersen H, Christensen J: Biomechanical characteristics of the human esophagus. Dig Dis Sci 38(2):197–205, 1993
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
Achem SR, DeVault KR: Unexplained chest pain at the turn of the century. Am J Gastroenterol 94(1):5–8, 1999
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
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
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
Rao SSC, Hayek, Summers RW: Unexplained chest pain: Esophageal hypersensitivity or motor dysfunction? Am J Gastroenterol 96(8):2584–2589, 2001
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
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
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
Krysiak PS, Preiksaitis HG: Tachykinins contribute to nerve mediated contractions in human esophagus. Gastroenterology 120:39–48, 2001
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
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
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
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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
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DOI: https://doi.org/10.1023/A:1021017524660