Background: Allergic symptoms can be induced by behavioral conditioning. However, the conditionability of antiallergic effects has not yet been studied. Thus, we investigated whether the effects of a histamine 1 (H1) receptor antagonist are inducible in patients suffering from house-dust mite allergy using a behavioral conditioning procedure. Methods: During the association phase, 30 patients with allergic house-dust mite rhinitis received a novel-tasting drink once daily, followed by a standard dose of the H1 receptor antagonist, desloratadine, on 5 consecutive days. After 9 days of drug washout, the evocation trial commenced: 10 patients received water together with an identically looking placebo pill (water group), 11 patients were re-exposed to the novel-tasting drink and received a placebo pill [conditioned stimulus (CS); CS group] and 9 patients received water and desloratadine (drug group). Results: During the association phase, desloratadine treatment decreased the subjective total symptom scores, attenuated the effects of the skin prick test for histamine and reduced basophil activation ex vivo in all groups. During the evocation trial, the water group, in which subjects were not re-exposed to the gustatory stimulus, showed a reduction in subjective total symptom scores and skin prick test results, but no inhibition of basophil activation. In contrast, re-exposure to the novel-tasting drink decreased basophil activation, the skin prick test result and the subjective symptom score in the CS group to a degree that was similar to the effects of desloratadine in the drug group. Conclusions: These data show that behaviorally conditioned effects are not only able to relieve subjective rhinitis symptoms and allergic skin reactions, but also to induce changes in effector immune functions.

Keywords:
Behavioral conditioning, Allergy, Desloratadine, House-dust mite, Placebo effect, Skin prick test, Basophil activation
1.
Wang DY, Goh DY, Ho AK, Chew F, Yeoh KH, Lee BW: The upper and lower airway responses to nasal challenge with house-dust mite Blomia tropicalis. Allergy 2003;58:78–82.
2.
Van Cauwenberge P: Advances in allergy management. Allergy 2002;75:29–36.
3.
Marshall GD: Neuroendocrine mechanisms of immune dysregulation: applications to allergy and asthma. Ann Allergy Asthma Immunol 2004;93:S11–S17.
4.
Langewitz W, Izakovic J, Wyler J, Schindler C, Kiss A, Bircher AJ: Effect of self-hypnosis on hay fever symptoms – A randomised controlled intervention study. Psychother Psychosom 2005;74:165–172.
5.
Elsenbruch S, Langhorst J, Popkirowa K, Muller T, Luedtke R, Franken U, Paul A, Spahn G, Michalsen A, Janssen OE, Schedlowski M, Dobos GJ: Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis. Psychother Psychosom 2005;74:277–287.
6.
Nickel C, Lahmann C, Muehlbacher M, Pedrosa Gil F, Kaplan P, Buschmann W, Tritt K, Kettler C, Bachler E, Egger C, Anvar J, Fartacek R, Loew T, Rother W, Nickel M: Pregnant women with bronchial asthma benefit from progressive muscle relaxation: a randomized, prospective, controlled trial. Psychother Psychosom 2006;75:237–243.
7.
Ryff CD, Dienberg Love G, Urry HL, Muller D, Rosenkranz MA, Friedman EM, Davidson RJ, Singer B: Psychological well-being and ill-being: do they have distinct or mirrored biological correlates? Psychother Psychosom 2006;75:85–95.
8.
Mackenzie JN: The production of the so-called ‘rose cold’ by means of an artificial rose. Am J Med Sci 1896;91:45–47.
9.
Hill LE: Philosophy of a Biologist. London, Arnold, 1930.
10.
Ader R, Cohen N: Behaviorally conditioned immunosuppression. Psychosom Med 1975;37:333–340.
11.
Ader R: Conditioning effects in pharmacotherapy and the incompleteness of the double-blind, crossover design. Integr Psychiatry 1989;6:165–170.
12.
Ader R: Conditioned immune responses and pharmacotherapy. Arthritis Care Res 1989;2:S58–S64.
13.
Ader R, Cohen N: Conditioning and immunity; in Ader R, Felten DL, Cohen N, (eds): Psychoneuroimmunology. New York, Academic Press, 2001, vol 2, pp 3–34.
14.
Exton MS, Herklotz J, Westermann J, Schedlowski M: Conditioning in the rat: an in vivo model to investigate the molecular mechanisms and clinical implications of brain-immune communication. Immunol Rev 2001;184:226–235.
15.
Goebel MU, Trebst AE, Steiner J, Xie YF, Exton MS, Frede S, Canbay A, Michel MC, Heemann U, Schedlowski M: Behavioral conditioning of immunosuppression is possible in humans. FASEB J 2002;16:1869–1873.
16.
Pacheco-Lopez G, Niemi MB, Kou W, Har-ting M, Fandrey J, Schedlowski M: Neural substrates for behaviorally conditioned immunosuppression in the rat. J Neurosci 2005;25:2330–2337.
17.
Pacheco-Lopez G, Engler H, Niemi MB, Schedlowski M: Expectations and associations that heal: immunomodulatory placebo effects and its neurobiology. Brain Behav Immun 2006;20:430–446.
18.
Suzuki R, Furuno T, McKay DM, Wolvers D, Teshima R, Nakanishi M, Bienenstock J: Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P. J Immunol 1999;163:2410–2415.
19.
Foreman JC, Jordan CC, Piotrowski W: Interaction of neurotensin with the substance P receptor mediating histamine release from rat mast cells and the flare in human skin. Br J Pharmacol 1982;77:531–539.
20.
Leff AR, Stimler NP, Munoz NM, Shioya T, Tallet J, Dame C: Augmentation of respiratory mast cell secretion of histamine caused by vagus nerve stimulation during antigen challenge. J Immunol 1986;136:1066–1073.
21.
Blennerhassett M, Bienenstock J: Sympathetic nerve contact causes maturation of mast cells in vitro. J Neurobiol 1998;35:173–182.
22.
MacQueen G, Marshall J, Perdue M, Siegel S, Bienenstock J: Pavlovian conditioning of rat mucosal mast cells to secrete rat mast cell protease II. Science 1989;243:83–85.
23.
Russell M, Dark KA, Cummins RW, Ellman G, Callaway E, Peeke HV: Learned histamine release. Science 1984;225:733–734.
24.
Peeke HV, Dark K, Ellman G, McCurry C, Salfi M: Prior stress and behaviorally conditioned histamine release. Physiol Behav 1987;39:89–93.
25.
Irie M, Nagata S, Endo Y: Fasting stress exacerbates classical conditioned histamine release in guinea pigs. Life Sci 2002;72:689–698.
26.
Gauci M, Husband AJ, Saxarra H, King MG: Pavlovian conditioning of nasal tryptase release in human subjects with allergic rhinitis. Physiol Behav 1994;55:823–825.
27.
Barrett JE, King MG, Pang G: Conditioning rhinitis in allergic humans. Ann NY Acad Sci 2000;917:853–859.
28.
Ader R: The role of conditioning in pharmacotherapy; in Harrington A (ed): The Placebo Effect: An Interdisciplinary Exploration. Cambridge, Harvard University Press, 1997, pp 138–165.
29.
Benedetti F, Mayberg HS, Wager TD, Stohler CS, Zubieta JK: Neurobiological mechanisms of the placebo effect. J Neurosci 2005;25:10390–10402.
30.
Colloca L, Benedetti F: Placebos and painkillers: is mind as real as matter? Nat Rev Neurosci 2005;6:545–552.
31.
Bachert C: Therapeutic points of intervention and clinical implications: role of desloratadine. Allergy 2002;75:13–18.
32.
Agrawal D: Pharmacology and clinical efficacy of desloratadine as an anti-allergic and anti-inflammatory drug. Expert Opin Investig Drugs 2001;10:547–560.
33.
Salmun LM, Lorber R: 24-hour efficacy of once-daily desloratadine therapy in patients with seasonal allergic rhinitis. BMC Fam Pract 2002;3:14.
34.
Luparello T, Lyons HA, Bleecker ER, McFadden ER: Influences of suggestion on airway reactivity in asthmatic subjects. Psychosom Med 1968;30:819–825.
35.
Luparello TJ, Leist N, Lourie CH, Sweet P: The interaction of psychologic stimuli and pharmacologic agents on airway reactivity in asthmatic subjects. Psychosom Med 1970;32:509–513.
36.
Markovic B, Djuric VJ, Lazarevic M, Janko-vic BD: Anaphylactic shock-induced conditioned taste aversion. 1. Demonstration of the phenomenon by means of three modes of CS-US presentation. Brain Behav Immun 1988;2:11–23.
37.
Bielory L, Lien KW, Bigelsen S: Efficacy and tolerability of newer antihistamines in the treatment of allergic conjunctivitis. Drugs 2005;65:215–228.
38.
Schroeder JT, Schleimer RP, Lichtenstein LM, Kreutner W: Inhibition of cytokine generation and mediator release by human basophils treated with desloratadine. Clin Exp Allergy 2001;31:1369–1377.
39.
Benedetti F, Pollo A, Lopiano L, Lanotte M, Vighetti S, Rainero I: Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses. J Neurosci 2003;23:4315–4323.
40.
Wager TD, Nitschke JB: Placebo effects in the brain: linking mental and physiological processes. Brain Behav Immun 2005;19:281–282.
41.
Marissen MA, Franken IH, Blanken P, van den Brink W, Hendriks VM: Cue exposure therapy for the treatment of opiate addiction: results of a randomized controlled clinical trial. Psychother Psychosom 2007;76:97–105.
42.
Jacobs KW, Nordan FM: Classification of placebo drugs: effect of color. Percept Mot Skills 1979;49:367–372.
43.
Zachariae R, Jorgensen MM, Egekvist H, Bjerring P: Skin reactions to histamine of healthy subjects after hypnotically induced emotions of sadness, anger, and happiness. Allergy 2001;56:734–740.
44.
Dhabhar FS: Stress, leukocyte trafficking, and the augmentation of skin immune function. Ann NY Acad Sci 2003;992:205–217.
45.
Exton MS, von Auer AK, Buske-Kirschbaum A, Stockhorst U, Goebel U, Schedlowski M: Pavlovian conditioning of immune function: animal investigation and the challenge of human application. Behav Brain Res 2000;110:129–141.
46.
Smith GR, McDaniel SM: Psychologically mediated effect on the delayed hypersensitivity reaction to tuberculin in humans. Psychosom Med 1983;45:65–70.
47.
Booth RJ, Petrie KJ, Brook RJ: Conditioning allergic skin responses in humans: a controlled trial. Psychosom Med 1995;57:492–495.
48.
Exton MS, Gierse C, Meier B, Mosen M, Xie Y, Frede S, Goebel MU, Limmroth V, Schedlowski M: Behaviorally conditioned immunosuppression in the rat is regulated via noradrenaline and beta-adrenoceptors. J Neuroimmunol 2002;131:21–30.
49.
Mori N, Suzuki R, Furuno T, McKay DM, Wada M, Teshima R, Bienenstock J, Nakanishi M: Nerve-mast cell (RBL) interaction: RBL membrane ruffling occurs at the contact site with an activated neurite. Am J Physiol Cell Physiol 2002;283:C1738–C1744.
50.
Hayashi T, Urayama O, Kawai K, Hayashi K, Iwanaga S, Ohta M, Saito T, Murakami K: Laughter regulates gene expression in patients with type 2 diabetes. Psychother Psychosom 2006;75:62–65.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.