DOI QR코드

DOI QR Code

Neuroimmunological Mechanism of Pruritus in Atopic Dermatitis Focused on the Role of Serotonin

  • Received : 2012.09.24
  • Accepted : 2012.10.16
  • Published : 2012.11.30

Abstract

Although pruritus is the critical symptom of atopic dermatitis that profoundly affect the patients' quality of life, controlling and management of prurirtus still remains as unmet needs mainly due to the distinctive multifactorial pathogenesis of pruritus in atopic dermatitis. Based on the distinct feature of atopic dermatitis that psychological state of patients substantially influence on the intensity of pruritus, various psychotropic drugs have been used in clinic to relieve pruritus of atopic dermatitis patients. Only several psychotropic drugs were reported to show real antipruritic effects in atopic dermatitis patients including naltrexone, doxepin, trimipramine, bupropion, tandospirone, paroxetine and fluvoxamine. However, the precise mechanisms of antipruritic effect of these psychotropic drugs are still unclear. In human skin, serotonin receptors and serotonin transporter protein are expressed on skin cells such as keratinocytes, melanocytes, dermal fibroblasts, mast cells, T cells, natural killer cells, langerhans cells, and sensory nerve endings. It is noteworthy that serotonergic drugs, as well as serotonin itself, showed immune-modulating effect. Fenfluramine, fluoxetine and 2, 5-dimethoxy-4-iodoamphetamine significantly decreased lymphocyte proliferation. It is still questionable whether these serotonergic drugs exert the immunosuppressive effects via serotonin receptor or serotonin transporter. All these clinical and experimental reports suggest the possibility that antipruritic effects of selective serotonin reuptake inhibitors in atopic dermatitis patients might be at least partly due to their suppressive effect on T cells. Further studies should be conducted to elucidate the precise mechanism of neuroimmunological interaction in pruritus of atopic dermatitis.

Keywords

References

  1. Andrew, D. and Craig, A. D. (2001) Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat. Neurosci. 4, 72-77. https://doi.org/10.1038/82924
  2. Aune, T. M., McGrath, K. M., Sarr, T., Bombara, M. P. and Kelley, K. A. (1993) Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine. J. Immunol. 151, 1175-1183.
  3. Aune, T. M., Golden, H. W. and McGrath, K. M. (1994) Inhibitors of serotonin synthesis and antagonists of serotonin 1A receptors inhibit T lymphocyte function in vitro and cell-mediated immunity in vivo. J. Immunol. 153, 489-498.
  4. Bilsborough, J., Leung, D. Y., Maurer, M., Howell, M., Boguniewicz, M., Yao, L., Storey, H., LeCiel, C., Harder, B. and Gross, J. A. (2006) IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J. Allergy Clin. Immunol. 117, 418-425. https://doi.org/10.1016/j.jaci.2005.10.046
  5. Buske-Kirschbaum, A., Geiben, A. and Hellhammer, D. (2001) Psychobiological aspects of atopic dermatitis: an overview. Psychother. Psychosom. 70, 6-16. https://doi.org/10.1159/000056219
  6. Cevikbas, F., Steinhoff, A., Homey, B. and Steinhoff M. (2007) Neuroimmune interactions in allergic skin diseases. Curr. Opin. Allergy Clin. Immunol. 7, 365-373. https://doi.org/10.1097/ACI.0b013e3282a644d2
  7. Cevikbas, F., Steinhoff, M. and Ikoma, A. (2011) Role of spinal neurotransmitter receptors in itch: new insights into therapies and drug development. CNS Neurosci. Ther. 17, 742-749 https://doi.org/10.1111/j.1755-5949.2010.00201.x
  8. Connor, T. J., Kelly, J. P. and Leonard, B. E. (2000) An assessment of the acute effects of serotonin releasers methylenedioxymethamphetamine, methylenedioxyamphetamine and fenfluramine on immunity in rats. Immunopharmacology 46, 223-235. https://doi.org/10.1016/S0162-3109(99)00180-0
  9. Cowden, J. M., Zhang, M., Dunford, P. J. and Thurmond, R. L. (2010) The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J. Invest. Dermatol. 130, 1023-1033. https://doi.org/10.1038/jid.2009.358
  10. Darsow, U., Scharein, E., Bromm, B. and Ring, J. (1997) Skin testing of the pruritogenic activity of histamine and cytokines (interleukin-2 and tumour necrosis factor-alpha) at the dermal-epidermal junction. Br. J. Dermatol. 137, 415-417. https://doi.org/10.1111/j.1365-2133.1997.tb03749.x
  11. de Mel, S., Nordlind, K., Holst, M., Frohm-Nilsson, M. and Lonne-Rahm, S. B. (2012) Polymorphisms in the serotonin transporter gene of patients with atopic dermatitis-association with personality traits related to high level of anxiety. Immunopharmacol. Immunotoxicol. 34, 534-538. https://doi.org/10.3109/08923973.2011.632636
  12. Diehn, F. and Tefferi, A. (2001) Pruritus in polycythaemia vera: prevalence, laboratory correlates and management. Br. J. Haematol. 115, 619-621. https://doi.org/10.1046/j.1365-2141.2001.03161.x
  13. Dijkstra, D., Leurs, R., Chazot, P., Shenton, F. C., Stark, H. and Werfel, T. and Gutzmer, R. (2007) Histamine downregulates monocyte CCL2 production through the histamine H4 receptor. J. Allergy Clin. Immunol. 120, 300-307. https://doi.org/10.1016/j.jaci.2007.03.024
  14. Drake, L. A. and Millikan, L. E. (1995) The antipruritic effect of 5% doxepin cream in patients with eczematous dermatitis. Doxepin Study Goup. Arch. Dermatol. 131, 1403-1408. https://doi.org/10.1001/archderm.1995.01690240065010
  15. Dunford, P. J., Williams, K. N., Desai, P. J., Karlsson, L., McQueen, D. and Thurmond, R. L. (2007) Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J. Allergy Clin. Immunol. 119, 176-183. https://doi.org/10.1016/j.jaci.2006.08.034
  16. Edgar V. A., Sterin-Borda, L., Cremaschi, G. A. and Genaro, A. M. (1999) Role of protein kinase C and cAMP in fluoxetine effects on human T-cell proliferation. Eur. J. Pharmacol. 372, 65-73. https://doi.org/10.1016/S0014-2999(99)00142-9
  17. El-Nour, H., Lundeberg, L., Abdel-Magid, N., Lonne-Rahm, S. B., Azmitia, E. C. and Nordlind, K. (2007) Serotonergic mechanisms in human allergic contact dermatitis. Acta Derm. Venereol. 87, 390-396. https://doi.org/10.2340/00015555-0288
  18. Elenkov, I. J. (2004) Glucocorticoids and the Th1/Th2 balance. Ann. N. Y. Acad. Sci. 1024, 138-146. https://doi.org/10.1196/annals.1321.010
  19. Faraj, B. A., Olkowski, Z. L. and Jackson, R. T. (1994) Expression of a high-affinity serotonin transporter in human lymphocytes. Int. J. Immunopharmacol. 16, 561-567. https://doi.org/10.1016/0192-0561(94)90107-4
  20. Frank, M. G., Hendricks, S. E., Johnson, D. R., Wieseler, J. L. and Burke, W. J. (1999) Antidepressants augment natural killer cell activity: in vivo and in vitro. Neuropsychobiology. 39, 18-24. https://doi.org/10.1159/000026555
  21. Gonzalez-Rey, E., Chorny, A. and Delgado, M. (2007) Regulation of immune tolerance by anti-inflammatory neuropeptides. Nat. Rev. Immunol. 7, 52-63. https://doi.org/10.1038/nri1984
  22. Gonzalez, E., Sanguino, R. M. and Franco, M. A. (2006). Bupropion in atopic dermatitis. Pharmacopsychiatry 39, 229. https://doi.org/10.1055/s-2006-951384
  23. Gordon, J. and Barnes, N. M. (2003) Lymphocytes transport serotonin and dopamine: agony or ecstasy? Trends Immunol. 24, 438-443. https://doi.org/10.1016/S1471-4906(03)00176-5
  24. Greaves, M. W. and Khalifa, N. (2004) Itch: more than skin deep. Int. Arch. Allergy Immunol. 135, 166-172. https://doi.org/10.1159/000080898
  25. Gutzmer, R., Mommert, S., Gschwandtner, M., Zwingmann, K., Stark, H. and Werfel, T. (2009) The histamine H4 receptor is functionally expressed on Th2 cells. J. Allergy Clin. Immunol. 123, 619-625. https://doi.org/10.1016/j.jaci.2008.12.1110
  26. Handwerker, H. O. and Schmelz, M. (2009) Pain: itch without pain-a labeled line for itch sensation? Nat. Rev. Neurol. 5, 640-641. https://doi.org/10.1038/nrneurol.2009.191
  27. Hanifin, J. M., Ling, M. R., Langley, R., Breneman, D. and Rafal, E. (2001) Tacrolimus ointment for the treatment of atopic dermatitis in adult patients: part I, efficacy. J. Am. Acad. Dermatol. 44, S28-S38. https://doi.org/10.1067/mjd.2001.109810
  28. Hennino, A., Jean-Decoster, C., Giordano-Labadie, F., Debeer, S., Vanbervliet, B., Rozieres, A., Schmitt, A. M. and Nicolas, J. F. (2011) CD8+ T cells are recruited early to allergen exposure sites in atopy patch test reactions in human atopic dermatitis. J. Allergy Clin. Immunol. 127, 1064-1067. https://doi.org/10.1016/j.jaci.2010.11.022
  29. Heyer, G. R. and Hornstein, O. P. (1999). Recent studies of cutaneous nociception in atopic and non-atopic subjects. J. Dermatol. 26, 77-86. https://doi.org/10.1111/j.1346-8138.1999.tb03516.x
  30. Hoare, C., Li Wan Po, A. and Williams, H. (2000) Systematic review of treatments for atopic eczema. Health Technol. Assess. 4, 1-191.
  31. Jameson, J., Ugarte, K., Chen, N., Yachi, P., Fuchs, E., Boismenu, R. and Havran, W. L. (2002) A role for skin gammadelta T cells in wound repair. Science 296, 747-749. https://doi.org/10.1126/science.1069639
  32. Jarvikallio, A., Harvima, I. T. and Naukkarinen, A. (2003) Mast cells, nerves and neuropeptides in atopic dermatitis and nummular eczema. Arch. Dermatol. Res. 295, 2-7. https://doi.org/10.1007/s00403-002-0378-z
  33. Kawana, S., Kato, Y. and Omi, T. (2010) Efficacy of a 5-HT1a receptor agonist in atopic dermatitis. Clin. Exp. Dermatol. 35, 835-840. https://doi.org/10.1111/j.1365-2230.2009.03771.x
  34. Klein, P. A. and Clark, R. A. (1999) An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis. Arch. Dermatol. 135, 1522-1525. https://doi.org/10.1001/archderm.135.12.1522
  35. Koblenzer, C. S. (1999) Itching and the atopic skin. J. Allergy Clin. Immunol. 104, S109-S113. https://doi.org/10.1016/S0091-6749(99)70052-7
  36. Kroeze, W. K., Kristiansen, K. and Roth, B. L. (2002) Molecular biology of serotonin receptors structure and function at the molecular level. Curr. Top. Med. Chem. 2, 507-528. https://doi.org/10.2174/1568026023393796
  37. Lee, C. H. (2010) Progress of pruritus research in atopic dermatitis. Biomol. Ther. 18, 246-256. https://doi.org/10.4062/biomolther.2010.18.3.246
  38. Lee, H. J., Park, M. K., Kim, S. Y., Park Choo H. Y., Lee, A. Y. and Lee, C. H. (2011) Serotonin induces melanogenesis via serotonin receptor 2A. Br. J. Dermatol. 165, 1344-1348. https://doi.org/10.1111/j.1365-2133.2011.10490.x
  39. Leung, D. Y. and Bieber, T. (2003) Atopic dermatitis. Lancet 361, 151-160. https://doi.org/10.1016/S0140-6736(03)12193-9
  40. Leung, D. M., Boguniewicz, M., Howell, M. D., Nomura, I. and Hamid, Q. A. (2004) New insights into atopic dermatitis. J. Clin. Invest. 113, 651-657. https://doi.org/10.1172/JCI21060
  41. Lonne-Rahm, S. B., Rickberg, H., El-Nour, H., Marin, P., Azmitia, E. C. and Nordlind, K. (2008) Neuroimmune mechanisms in patients with atopic dermatitis during chronic stress. J. Eur. Acad. Dermatol. Venereol. 22, 11-18.
  42. Luger, T. A. (2002) Neuromediators - a crucial component of the skin immune system. J. Dermatol. Sci. 30, 87-93. https://doi.org/10.1016/S0923-1811(02)00103-2
  43. Luger, T., Van Leent, E. J., Graeber, M., Hedgecock, S., Thurston, M., Kandra, A., Berth-Jones, J., Bjerke, J., Christophers, E., Knop, J., Knulst, A. C., Morren, M., Morris, A., Reitamo, S., Roed-Petersen, J., Schoepf, E., Thestrup-Pedersen, K., Van Der Valk, P. G. and Bos, J. D. (2001) SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis. Br. J. Dermatol. 144, 788-794. https://doi.org/10.1046/j.1365-2133.2001.04134.x
  44. Meredith, E. J., Chamba, A., Holder, M. J., Barnes, N. M. and Gordon, J. (2005) Close encounters of the monoamine kind: immune cells betray their nervous disposition. Immunology 115, 289-295. https://doi.org/10.1111/j.1365-2567.2005.02166.x
  45. Metz, M., Grundmann, S. and Stander, S. (2011) Pruritus: an overview of current concepts. Veterinary. Dermatology 22, 121-131.
  46. Mommert, S., Gschwandtner, M., Gutzmer, R. and Werfel, T. (2011) The role of the histamine H4 receptor in atopic dermatitis. Curr. Allergy Asthma Rep. 11, 21-28. https://doi.org/10.1007/s11882-010-0162-7
  47. Morren, M. A., Przybilla, B., Bamelis, M., Heykants, B., Reynaers, A. and Degreef, H. (1994) Atopic dermatitis: triggering factors. J. Am. Acad. Dermatol. 31, 467-473. https://doi.org/10.1016/S0190-9622(94)70213-6
  48. Mossner, R. and Lesch, K. P. (1998) Role of serotonin in the immune system and in neuroimmune interactions. Brain. Behav. Immun. 12, 249-271. https://doi.org/10.1006/brbi.1998.0532
  49. Nakano, T., Andoh, T., Lee, J. B. and Kuraishi, Y. (2008) Different dorsal horn neurons responding to histamine and allergic itch stimuli. Neuroreport 19, 723-726. https://doi.org/10.1097/WNR.0b013e3282fdf6c5
  50. Novak, N. and Leung, D. Y. (2011) Advances in atopic dermatitis. Curr. Opin. Immunol. 23, 778-783. https://doi.org/10.1016/j.coi.2011.09.007
  51. Pastar, Z., Lipozencic, J. and Ljubojevic S. (2005) Etiopathogenesis of atopic dermatitis - an overview. Acta Dermatovenerol. Croat. 13, 54-62.
  52. Paus, R., Schmelz, M., Biro, T. and Steinhoff, M. (2006) Frontiers in pruritus research: scratching the brain for more effective itch therapy. J. Clin. Invest. 116, 1174-1186. https://doi.org/10.1172/JCI28553
  53. Pellegrino, T. C. and Bayer, B. M. (2000) Specific serotonin reuptake inhibitor-induced decreases in lymphocyte activity require endogenous serotonin release. Neuroimmunomodulation 8, 179-187. https://doi.org/10.1159/000054278
  54. Pellegrino, T. C. and Bayer, B. M. (2002) Role of central 5-HT (2) receptors in fluoxetine-induced decreases in T lymphocyte activity. Brain Behav. Immun. 16, 87-103. https://doi.org/10.1006/brbi.2001.0625
  55. Roosterman, D., Goerge, T., Schneider, S.W., Bunnett, N. W. and Steinhoff, M. (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol. Rev. 86, 1309-1379. https://doi.org/10.1152/physrev.00026.2005
  56. Rudd, M. L., Nicolas, A. N., Brown, B. L., Fischer-Stenger, K. and Stewart, J. K. (2005) Peritoneal macrophages express the serotonin transporter. J. Neuroimmunol. 159, 113-118. https://doi.org/10.1016/j.jneuroim.2004.10.013
  57. Rukwied, R., Lischetzki, G., McGlone, F., Heyer, G. and Schmelz, M. (2000) Mast cell mediators other than histamine induce pruritus in atopic dermatitis patients: a dermal microdialysis study. Br. J. Dermatol. 142, 1114-1120. https://doi.org/10.1046/j.1365-2133.2000.03535.x
  58. Savin, J. A., Paterson, W. D., Adam, K. and Oswald, I. (1979) Effects of trimeprazine and trimipramine on nocturnal scratching in patients with atopic eczema. Arch. Dermatol.115, 313-315. https://doi.org/10.1001/archderm.1979.04010030021008
  59. Schmelz, M. (2001) A neural pathway for itch. Nat. Neurosci. 4, 9-10. https://doi.org/10.1038/82956
  60. Schmelz, M., Hilliges, M., Schmidt, R., Orstavik, K., Vahlquist, C., Weidner, C., Handwerker, H. O. and Torebjork, H. E. (2003) Active "itch fibers" in chronic pruritus. Neurology 61, 564-566. https://doi.org/10.1212/01.WNL.0000078193.64949.08
  61. Seuwen, K. and Pouyssegur, J. (1990) Serotonin as a growth factor. Biochem. Pharmacol. 39, 985-990. https://doi.org/10.1016/0006-2952(90)90276-Q
  62. Sharp, L. L., Jameson, J. M., Witherden, D. A., Komori, H. K. and Havran, W. L. (2005) Dendritic epidermal T-cell activation. Crit. Rev. Immunol. 25, 1-18. https://doi.org/10.1615/CritRevImmunol.v25.i1.10
  63. Shimoda, T., Liang, Z., Suzuki, H. and Kawana, S. (2010) Inhibitory effects of antipsychotic and anxiolytic agents on stress induced degranulation of mouse dermal mast cells. Clin. Exp. Dermatol. 35, 531-536.
  64. Slominski, A., Pisarchik, A., Zbytek, B., Tobin, D. J., Kauser, S. and Wortsman, J. (2003) Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J. Cell. Physiol. 196, 144-153. https://doi.org/10.1002/jcp.10287
  65. Slominski, A., Wortsman, J. and Tobin, D. J. (2005) The cutaneous serotonergic/melatonergic system: securing a place under the sun. FASEB J. 19, 176-194. https://doi.org/10.1096/fj.04-2079rev
  66. Sonkoly, E., Muller, A., Lauerma, A. I., Pivarcsi, A., Soto, H., Kemeny, L., Alenius, H., Dieu-Nosjean, M. C., Meller, S., Rieker, J., Steinhoff, M., Hoffmann, T. K., Ruzicka, T., Zlotnik, A. and Homey, B. (2006) IL-31: A new link between T cells and pruritus in atopic skin inflammation. J. Allergy Clin. Immunol. 117, 411-417. https://doi.org/10.1016/j.jaci.2005.10.033
  67. Stander, S., Gunzer, M., Metze, D., Luger, T. and Steinhoff, M. (2002) Localization of mu-opioid receptor 1A on sensory nerve fibers in human skin. Regul. Pept. 110, 75-83. https://doi.org/10.1016/S0167-0115(02)00159-3
  68. Stander, S., Weisshaar, E. and Luger, T. A. (2008) Neurophysiological and neurochemical basis of modern pruritus treatment. Exp. Dermatol. 17, 161-169. https://doi.org/10.1111/j.1600-0625.2007.00664.x
  69. Stander, S., Bockenholt, B., Schurmeyer-Horst, F., Weishaupt, C., Heuft, G., Luger, T. A. and Schneider, G. (2009) Treatment of chronic pruritus with the selective serotonin re-uptake inhibitors paroxetine and fluvoxamine: results of an open-labelled, two-arm proof-of concept study. Acta Derm. Venereol. 89, 45-51 https://doi.org/10.2340/00015555-0553
  70. Steinhoff, M., Bienenstock, J., Schmelz, M., Maurer, M., Wei, E. and Biro, T. (2006) Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. J. Invest. Dermatol. 126, 1705-1718. https://doi.org/10.1038/sj.jid.5700231
  71. Straub, R. H. (2004) Complexity of the bi-directional neuroimmune junction in the spleen. Trends Pharmacol. Sci. 25, 640-646. https://doi.org/10.1016/j.tips.2004.10.007
  72. Strid, J., Tigelaar, R. E. and Hayday, A. C. (2009) Skin immune surveillance by T cells--a new order? Semin. Immunol. 21, 110-120. https://doi.org/10.1016/j.smim.2009.03.002
  73. Sugimoto, Y., Iba, Y., Nakamura, Y., Kayasuga, R. and Kamei C. (2004) Pruritus-associated response mediated by cutaneous histamine H3 receptors. Clin. Exp. Allergy 34, 456-459. https://doi.org/10.1111/j.1365-2222.2004.01876.x
  74. Tobin, D., Nabarro, G., Baart de la Faille, H., van Vloten, W. A., van der Putte, S. C. and Schuurman, H. J. (1992) Increased number of immunoreactive nerve fibers in atopic dermatitis. J. Allergy Clin. Immunol. 90, 613-622. https://doi.org/10.1016/0091-6749(92)90134-N
  75. Turner, D. J., Martin, P. C., Rao, J. N., Greenspon, J., Zou, T., Bass, B. L., Wang, J. Y. and Strauch, E. D. (2007) Substance P regulates migration in rat intestinal epithelial cells. Ann. Surg. 245, 408-414. https://doi.org/10.1097/01.sla.0000245549.57076.db
  76. Urashima, R. and Mihara, M. (1998) Cutaneous nerves in atopic dermatitis. A histological, immunohistochemical and electron microscopic study. Virchows. Arch. 432, 363-370. https://doi.org/10.1007/s004280050179
  77. Wahlgren, C. F., Scheynius, A. and Hägemark, O. (1990) Antipruritic effect of oral cyclosporin A in atopic dermatitis. Acta. Derm. Venereol. 70, 323-329.
  78. Wahlgren, C. F. (1992) Pathophysiology of itching in urticaria and atopic dermatitis. Allergy 47, 65-75. https://doi.org/10.1111/j.1398-9995.1992.tb05091.x
  79. Wahlgren, C. F., Tengvall, Linder, M., Hagemark, O. and Scheynius, A. (1995) Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects. Arch. Dermatol. Res. 287, 572-580. https://doi.org/10.1007/BF00374079
  80. Weidinger, S., Gieger, C., Rodriguez, E., Baurecht, H., Mempel, M., Klopp, N., Gohlke, H., Waqenpfeil, S., Ollert, M., Ring, J., Behrendt, H., Heinrich, J., Novak, N., Bieber, T., Kramer, U., Berdel, D., von Berg, A., Bauer, C. P., Herbarth, O., Koletzko, S., Prokisch, H., Mehta, D., Meitinger, T., Depner, M., von Mutius, E., Liang, L., Moffatt, M., Cookson, W., Kabesch, M., Wichmann, H. E. and Illig, T. (2008) Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS. Genet. 4, e1000166. https://doi.org/10.1371/journal.pgen.1000166
  81. Weisshaar, E., Ziethen, B. and Gollnick, H. (1997) Can a serotonin type 3 (5-HT3) receptor antagonist reduce experimentally-induced itch? Inflamm. Res. 46, 412-416 https://doi.org/10.1007/s000110050213
  82. Witherden, D. A., Verdino, P., Rieder, S. E., Garijo, O., Mills, R. E., Teyton, L., Fischer, W. H., Wilson, I. A. and Havran, W. L. (2010) The junctional adhesion molecule JAML is a costimulatory receptor for epithelial gammadelta T cell activation. Science 329, 1205-1210. https://doi.org/10.1126/science.1192698
  83. Yamaguchi, T., Nagasawa, T., Satoh, M. and Kuraishi, Y. (1999) Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice. Neurosci. Res. 35, 77-83. https://doi.org/10.1016/S0168-0102(99)00070-X
  84. Yaris, E., Kesim, M., Kadioglu, M., Kalyoncu, N. I., Ulku, C. and Ozyavuz, R. (2003) The effects of paroxetine on rat isolated vas deferens. Pharmacol. Res. 48, 335-345. https://doi.org/10.1016/S1043-6618(03)00157-9
  85. Yosipovitch, G., Szolar, C., Hui, X. Y. and Maibach, H. (1996) High-potency topical corticosteroid rapidly decreases histamine-induced itch but not thermal sensation and pain in human beings. J. Am. Acad. Dermatol. 35, 118-120. https://doi.org/10.1016/S0190-9622(96)90524-1
  86. Zylicz, Z., Krajnik, M., Sorge, A. A. and Costantini, M. (2003) Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial. J. Pain. Symptom Manage. 26, 1105-1112. https://doi.org/10.1016/j.jpainsymman.2003.05.004

Cited by

  1. Itch in Atopic Dermatitis vol.37, pp.1, 2017, https://doi.org/10.1016/j.iac.2016.08.007
  2. Curine inhibits mast cell-dependent responses in mice vol.155, pp.2, 2014, https://doi.org/10.1016/j.jep.2014.06.041
  3. Therapeutic action of 5-HT3receptor antagonists targeting peritoneal macrophages in post-operative ileus vol.172, pp.4, 2015, https://doi.org/10.1111/bph.13006
  4. Nalbuphine for Treatment of Opioid-induced Pruritus vol.32, pp.1, 2016, https://doi.org/10.1097/AJP.0000000000000211
  5. Mast Cell Serotonin Immunoregulatory Effects Impacting on Neuronal Function: Implications for Neurodegenerative and Psychiatric Disorders vol.28, pp.2, 2015, https://doi.org/10.1007/s12640-015-9533-0
  6. Anti-Allergic Properties of Curine, a Bisbenzylisoquinoline Alkaloid vol.20, pp.3, 2015, https://doi.org/10.3390/molecules20034695
  7. A review of itch vol.12, pp.2, 2015, https://doi.org/10.1097/01.EWX.0000462665.35251.a1
  8. Anxiety and Atopic Disease: Comorbidity in a Youth Mental Health Setting vol.48, pp.4, 2017, https://doi.org/10.1007/s10578-016-0678-8
  9. Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder vol.137, pp.1, 2017, https://doi.org/10.1016/j.jid.2016.08.022
  10. The efficacy of whey associated with dodder seed extract on moderate-to-severe atopic dermatitis in adults: A randomized, double-blind, placebo-controlled clinical trial vol.172, 2015, https://doi.org/10.1016/j.jep.2015.07.003
  11. Canine models of allergic skin disease vol.27, pp.4, 2016, https://doi.org/10.1111/vde.12311
  12. Novel inhibitory effects of cardamonin on thromboxane A2-induced scratching response: Blocking of Gh/transglutaminase-2 binding to thromboxane A2 receptor vol.126, 2014, https://doi.org/10.1016/j.pbb.2014.09.011
  13. Prevention of Photocarcinogenesis by Agonists of 5-HT1A and Antagonists of 5-HT2A Receptors vol.53, pp.2, 2016, https://doi.org/10.1007/s12035-014-9068-z
  14. Treatment of Atopic Dermatitis From the Perspective of Traditional Persian Medicine vol.22, pp.1, 2017, https://doi.org/10.1177/2156587215598610
  15. Comparison of pregabalin with ondansetron in treatment of uraemic pruritus in dialysis patients: a prospective, randomized, double-blind study vol.47, pp.1, 2015, https://doi.org/10.1007/s11255-014-0795-x
  16. Glycomacropeptide Attenuates Inflammation, Pruritus, and Th2 Response Associated with Atopic Dermatitis Induced by 2,4-Dinitrochlorobenzene in Rat vol.2017, 2017, https://doi.org/10.1155/2017/6935402
  17. Allergic Airway-Induced Hypersensitivity Is Attenuated by Bergapten in Murine Models of Inflammation vol.2019, pp.1687-6342, 2019, https://doi.org/10.1155/2019/6097349
  18. Effect of conjugated linoleic acid on compound 48/80-induced pruritus in mice vol.15, pp.3, 2012, https://doi.org/10.12729/jbr.2014.15.3.123
  19. 아토피 피부염과 심리적 요인에 대한 동서의학적 고찰 vol.32, pp.2, 2012, https://doi.org/10.15188/kjopp.2018.04.32.2.113
  20. The expression of serotonin transporter protein in the skin of patients with chronic spontaneous urticaria and its relation with depression and anxiety vol.311, pp.10, 2012, https://doi.org/10.1007/s00403-019-01969-y