NK-1 Antagonists and Itch

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 226)

Abstract

Substance P (SP) is an important mediator of pro-inflammatory mechanisms in the skin. It targets multiple cells such as keratinocytes, mast cells, and fibroblasts which are involved in the cutaneous generation of pruritus. This suggests that SP is an interesting target for therapy. In fact, in recent case reports and case series, SP antagonists demonstrated a significant antipruritic effect in acute and chronic pruritus such as drug-induced pruritus, paraneoplastic pruritus, prurigo nodularis, cutaneous T-cell lymphoma, and brachioradial pruritus.

Keywords

Antagonist Antinociception G protein-coupled receptor Keratinocyte Mast cell Neurokinin-1 receptor Neuropeptides Pruritus Prurigo Sensory C-fiber Substance P Skin Tachykinins 

Abbreviations

ACE

Angiotensin-converting enzyme

AD

Atopic dermatitis

CGRP

Calcitonin gene-related peptide

CMH fibers

Mechano- and heat-sensitive C-nerve fibers

CMi fibers

Mechano-insensitive C-nerve fibers

CNS

Central nervous system

CP

Chronic pruritus

CRH

Corticotropin-releasing hormone

CRHR-1

Corticotropin-releasing hormone receptor-1

CRPS

Complex regional pain syndrome

DNFB

Dinitrofluorobenzene

H1

Histamine-1 receptor

IL

Interleukin

MC

Mast cell

NEP

Neutral endopeptidase

NGF

Nerve growth factor

NK1R

Neurokinin-1 receptor

NK2R

Neurokinin-2 receptor

NK3R

Neurokinin-3 receptor

NKA

Neurokinin A

NKB

Neurokinin B

NKγ

Neuropeptide-γ

NPK

Neuropeptide K

PN

Prurigo nodularis

PPTA

Preprotachykinin-A

SP

Substance P

TNF

Tumor necrosis factor

TRPV1

Transient receptor potential vanilloid subtype 1

VEGF

Vascular endothelial growth factor

References

  1. Abadía Molina F, Burrows NP, Jones RR, Terenghi G, Polak JM (1992) Increased sensory neuropeptides in nodular prurigo: a quantitative immunohistochemical analysis. Br J Dermatol 127:344–351PubMedCrossRefGoogle Scholar
  2. Akiyama T, Tominaga M, Davoodi A, Nagamine M, Blansit K, Horwitz A, Carstens MI, Carstens E (2013) Roles for substance P and gastrin-releasing peptide as neurotransmitters released by primary afferent pruriceptors. J Neurophysiol 109:742–748PubMedCentralPubMedCrossRefGoogle Scholar
  3. Ally MS, Gamba CS, Peng DH, Tang JY (2013) The use of aprepitant in brachioradial pruritus. JAMA Dermatol 149:627–628PubMedCrossRefGoogle Scholar
  4. Alysandratos KD, Asadi S, Angelidou A, Zhang B, Sismanopoulos N, Yang H, Critchfield A, Theoharides TC (2012) Neurotensin and CRH interactions augment human mast cell activation. PLoS One 7:e48934PubMedCentralPubMedCrossRefGoogle Scholar
  5. Amatya B, Nordlind K, Wahlgren CF (2010) Responses to intradermal injections of substance P in psoriasis patients with pruritus. Skin Pharmacol Physiol 23:133–138PubMedCrossRefGoogle Scholar
  6. Andoh T, Kuraishi Y (2002) Inhibitory effects of azelastine on substance P-induced itch-associated response in mice. Eur J Pharmacol 436:235–239PubMedCrossRefGoogle Scholar
  7. Andoh T, Nagasawa T, Satoh M, Kuraishi Y (1998) Substance P induction of itch-associated response mediated by cutaneous NK1 tachykinin receptors in mice. J Pharmacol Exp Ther 286:1140–1145PubMedGoogle Scholar
  8. Andoh T, Katsube N, Maruyama M, Kuraishi Y (2001) Involvement of leukotriene B(4) in substance P-induced itch-associated response in mice. J Invest Dermatol 117:1621–1626PubMedCrossRefGoogle Scholar
  9. Asadi S, Alysandratos KD, Angelidou A, Miniati A, Sismanopoulos N, Vasiadi M, Zhang B, Kalogeromitros D, Theoharides TC (2012) Substance P (SP) induces expression of functional corticotropin-releasing hormone receptor-1 (CRHR-1) in human mast cells. J Invest Dermatol 132:324–329PubMedCentralPubMedCrossRefGoogle Scholar
  10. Benecke H, Lotts T, Ständer S (2013a) Investigational drugs for pruritus. Expert Opin Investig Drugs 22:1167–1179PubMedCrossRefGoogle Scholar
  11. Benecke H, Wäring J, Ständer S (2013b) Transient receptor potential channels and pruritus. In: Bíró T, Szallasi A (eds) TRP channels in drug discovery, vol 2, Methods in pharmacology and toxicology series. Springer/Humana, New York, pp 255–277Google Scholar
  12. Böhm SK, Khitin LM, Smeekens SP, Grady EF, Payan DG, Bunnett NW (1997) Identification of potential tyrosine-containing endocytic motifs in the carboxyl-tail and seventh transmembrane domain of the neurokinin 1 receptor. J Biol Chem 272:2363–2372PubMedCrossRefGoogle Scholar
  13. Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J (2011) Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol 164:665–667PubMedGoogle Scholar
  14. Bowden JJ, Garland AM, Baluk P, Lefevre P, Grady EF, Vigna SR, Bunnett NW, McDonald DM (1994) Direct observation of substance P-induced internalization of neurokinin 1 (NK1) receptors at sites of inflammation. Proc Natl Acad Sci USA 91:8964–8968PubMedCentralPubMedCrossRefGoogle Scholar
  15. Burbach GJ, Kim KH, Zivony AS, Kim A, Aranda J, Wright S, Naik SM, Caughman SW, Ansel JC, Armstrong CA (2001) The neurosensory tachykinins substance P and neurokinin A directly induce keratinocyte nerve growth factor. J Invest Dermatol 117:1075–1082PubMedCrossRefGoogle Scholar
  16. Carstens EE, Carstens MI, Simons CT, Jinks SL (2010) Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport 21:303–308PubMedCentralPubMedCrossRefGoogle Scholar
  17. Chang SE, Han SS, Jung HJ, Choi JH (2007) Neuropeptides and their receptors in psoriatic skin in relation to pruritus. Br J Dermatol 156:1272–1277PubMedCrossRefGoogle Scholar
  18. Dando TM, Perry C (2004) Aprepitant: a review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 64:777–794PubMedCrossRefGoogle Scholar
  19. Datar P, Srivastava S, Coutinho E, Govil G (2004) Substance P: structure, function, and therapeutics. Curr Top Med Chem 4:75–103PubMedCrossRefGoogle Scholar
  20. DeVane CL (2001) Substance P: a new era, a new role. Pharmacotherapy 21:1061–1069PubMedCrossRefGoogle Scholar
  21. Duval A, Dubertret L (2009) Aprepitant as an antipruritic agent? N Engl J Med 361:1415–1416PubMedCrossRefGoogle Scholar
  22. Gerber PA, Buhren BA, Homey B (2011) More on aprepitant for erlotinib-induced pruritus. N Engl J Med 364:486–487PubMedCrossRefGoogle Scholar
  23. Green SA, Alon A, Ianus J, McNaughton KS, Tozzi CA, Reiss TF (2006) Efficacy and safety of a neurokinin-1 receptor antagonist in postmenopausal women with overactive bladder with urge urinary incontinence. J Urol 176:2535–2540PubMedCrossRefGoogle Scholar
  24. Haas S, Capellino S, Phan NQ, Böhm M, Luger TA, Straub RH, Ständer S (2010) Low density of sympathetic nerve fibers relative to substance P-positive nerve fibers in lesional skin of chronic pruritus and prurigo nodularis. J Dermatol Sci 58:193–197PubMedCrossRefGoogle Scholar
  25. Hägermark O, Hökfelt T, Pernow B (1978) Flare and itch induced by substance P in human skin. J Invest Dermatol 71:233–235PubMedCrossRefGoogle Scholar
  26. Harmar AJ, Armstrong A, Pascall JC, Chapman K, Rosie R, Curtis A, Going J, Edwards CRW, Fink G (1986) cDNA sequence of human beta-preprotachykinin, the common precursor to substance P and neurokinin A. FEBS Lett 208:67–72PubMedCrossRefGoogle Scholar
  27. Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ, Aprepitant Protocol 052 Study Group (2003) The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol 052 Study Group. J Clin Oncol 21:4077–4080CrossRefGoogle Scholar
  28. Hon KL, Lam MC, Wong KY, Leung TF, Ng PC (2007) Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P. Br J Dermatol 157:922–925PubMedCrossRefGoogle Scholar
  29. Hosokawa C, Takeuchi S, Furue M (2009) Severity scores, itch scores and plasma substance P levels in atopic dermatitis treated with standard topical therapy with oral olopatadine hydrochloride. J Dermatol 36:185–190PubMedCrossRefGoogle Scholar
  30. Ikoma A, Steinhoff M, Ständer S, Yosipovitch G, Schmelz M (2006) The neurobiology of itch. Nat Rev Neurosci 7:535–547PubMedCrossRefGoogle Scholar
  31. Imamachi N, Park GH, Lee H, Anderson DJ, Simon MI, Basbaum AI, Han SK (2009) TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proc Natl Acad Sci USA 106:11330–11335PubMedCentralPubMedCrossRefGoogle Scholar
  32. Inagaki N, Shiraishi N, Igeta K, Nagao M, Kim JF, Chikumoto T, Itoh T, Katoh H, Tanaka H, Nagai H (2010) Depletion of substance P, a mechanism for inhibition of mouse scratching behavior by tacrolimus. Eur J Pharmacol 626:283–289PubMedCrossRefGoogle Scholar
  33. Janelsins BM, Mathers AR, Tkacheva OA, Erdos G, Shufesky WJ, Morelli AE, Larregina AT (2009) Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity. Blood 113:3017–3026PubMedCentralPubMedCrossRefGoogle Scholar
  34. Janelsins BM, Sumpter TL, Tkacheva OA, Rojas-Canales DM, Erdos G, Mathers AR, Shufesky WJ, Storkus WJ, Falo LD Jr, Morelli AE, Larregina AT (2013) Neurokinin-1 receptor agonists bias therapeutic dendritic cells to induce type 1 immunity by licensing host dendritic cells to produce IL-12. Blood 121:2923–2933PubMedCentralPubMedCrossRefGoogle Scholar
  35. Järvikallio A, Harvima IT, Naukkarinen A (2003) Mast cells, nerves and neuropeptides in atopic dermatitis and nummular eczema. Arch Dermatol Res 295:2–7PubMedGoogle Scholar
  36. Johanek LM, Meyer RA, Hartke T, Hobelmann JG, Maine DN, LaMotte RH, Ringkamp M (2007) Psychophysical and physiological evidence for parallel afferent pathways mediating the sensation of itch. J Neurosci 27:7490–7497PubMedCrossRefGoogle Scholar
  37. Kähler CM, Sitte BA, Reinisch N, Wiedermann CJ (1993) Stimulation of the chemotactic migration of human fibroblasts by substance P. Eur J Pharmacol 249:281–286PubMedCrossRefGoogle Scholar
  38. Kawana S, Liang Z, Nagano M, Suzuki H (2006) Role of substance P in stress-derived degranulation of dermal mast cells in mice. J Dermatol Sci 42:47–54PubMedCrossRefGoogle Scholar
  39. Keller M, Montgomery S, Ball W, Morrison M, Snavely D, Liu G, Hargreaves R, Hietala J, Lines C, Beebe K, Reines S (2006) Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry 59:216–223PubMedCrossRefGoogle Scholar
  40. Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hale JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Carlson EJ, Hargreaves RJ, Rupniak NM (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281:1640–1645PubMedCrossRefGoogle Scholar
  41. Kremer AE, van Dijk R, Leckie P, Schaap FG, Kuiper EM, Mettang T, Reiners KS, Raap U, van Buuren HR, van Erpecum KJ, Davies NA, Rust C, Engert A, Jalan R, Oude Elferink RP, Beuers U (2012) Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions. Hepatology 56:1391–1400PubMedCrossRefGoogle Scholar
  42. Kumagai H, Ebata T, Takamori K, Muramatsu T, Nakamoto H, Suzuki H (2010) Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant 25:1251–1257PubMedCrossRefGoogle Scholar
  43. Lai JP, Ho WZ, Kilpatrick LE, Wang X, Tuluc F, Korchak HM, Douglas SD (2006) Full-length and truncated neurokinin-1 receptor expression and function during monocyte/macrophage differentiation. Proc Natl Acad Sci USA 103:7771–7776PubMedCentralPubMedCrossRefGoogle Scholar
  44. LaMotte RH, Shimada SG, Green BG, Zelterman D (2009) Pruritic and nociceptive sensations and dysesthesias from a spicule of cowhage. J Neurophysiol 101:1430–1443PubMedCentralPubMedCrossRefGoogle Scholar
  45. Lee JH, Cho SH (2011) Korean red ginseng extract ameliorates skin lesions in NC/Nga mice: an atopic dermatitis model. J Ethnopharmacol 133:810–817PubMedCrossRefGoogle Scholar
  46. Levêque D (2010) Aprepitant for erlotinib-induced pruritus. N Engl J Med 363:1680–1681PubMedCrossRefGoogle Scholar
  47. Li WW, Guo TZ, Liang DY, Sun Y, Kingery WS, Clark JD (2012) Substance P signaling controls mast cell activation, degranulation, and nociceptive sensitization in a rat fracture model of complex regional pain syndrome. Anesthesiology 116:882–95PubMedCentralPubMedCrossRefGoogle Scholar
  48. Liu T, Ji RR (2013) New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms? Pflugers Arch 465:1671–1685PubMedCrossRefGoogle Scholar
  49. Liu JY, Zhao YZ, Peng C, Li FQ, Zhu QG, Hu JH (2008) Effect of cetirizine hydrochloride on the expression of substance P receptor and cytokines production in human epidermal keratinocytes and dermal fibroblasts. Yao Xue Xue Bao 43:383–387PubMedGoogle Scholar
  50. Maintz L, Wardelmann E, Walgenbach K, Fimmers R, Bieber T, Raap U, Novak N (2011) Neuropeptide blood levels correlate with mast cell load in patients with mastocytosis. Allergy 66:862–869PubMedCrossRefGoogle Scholar
  51. Matterne U, Apfelbacher CJ, Loerbroks A, Schwarzer T, Büttner M, Ofenloch R, Diepgen TL, Weisshaar E (2011) Prevalence, correlates and characteristics of chronic pruritus: a population-based cross-sectional study. Acta Derm Venereol 91:674–679PubMedGoogle Scholar
  52. Mir O, Coriat R (2012) Aprepitant for pruritus: drug-drug interactions matter. Lancet Oncol 13:964–965PubMedCrossRefGoogle Scholar
  53. Mir O, Blanchet B, Goldwasser F (2011) More on aprepitant for erlotinib-induced pruritus. N Engl J Med 364:487PubMedGoogle Scholar
  54. Muñoz M, Rosso M, Robles-Frias MJ, Salinas-Martín MV, Rosso R, González-Ortega A, Coveñas R (2010) The NK-1 receptor is expressed in human melanoma and is involved in the antitumor action of the NK-1 receptor antagonist aprepitant on melanoma cell lines. Lab Invest 90:1259–1269PubMedCrossRefGoogle Scholar
  55. Nakamura M, Toyoda M, Morohashi M (2003) Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors. Br J Dermatol 149:718–730PubMedCrossRefGoogle Scholar
  56. Nazarian A, Tenayuca JM, Almasarweh F, Armendariz A, Are D (2014) Sex differences in formalin-evoked primary afferent release of substance P. Eur J Pain 18:39–46PubMedCrossRefGoogle Scholar
  57. Ohmura T, Hayashi T, Satoh Y, Konomi A, Jung B, Satoh H (2004) Involvement of substance P in scratching behaviour in an atopic dermatitis model. Eur J Pharmacol 491:191–194PubMedCrossRefGoogle Scholar
  58. Orel M, Padrós E, Manyosa J (2012) Structural features of the C-terminus from the human neurokinin-1 receptor. FEBS J 279(13):2357–2367PubMedCrossRefGoogle Scholar
  59. Patacchini R, Lecci A, Holzer P, Maggi CA (2004) Newly discovered tachykinins raise new questions about their peripheral roles and the tachykinin nomenclature. Trends Pharmacol Sci 25:1–3PubMedCrossRefGoogle Scholar
  60. Pavlovic S, Daniltchenko M, Tobin DJ, Hagen E, Hunt SP, Klapp BF, Arck PC, Peters EM (2008) Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice. J Invest Dermatol 128:434–446PubMedCrossRefGoogle Scholar
  61. Peters EM, Liotiri S, Bodó E, Hagen E, Bíró T, Arck PC, Paus R (2007) Probing the effects of stress mediators on the human hair follicle: substance P holds central position. Am J Pathol 171:1872–1886PubMedCentralPubMedCrossRefGoogle Scholar
  62. Ping F, Shang J, Zhou J, Song J, Zhang L (2012) Activation of neurokinin-1 receptor by substance P inhibits melanogenesis in B16-F10 melanoma cells. Int J Biochem Cell Biol 44:2342–2348PubMedCrossRefGoogle Scholar
  63. Pogatzki-Zahn E, Marziniak M, Schneider G, Luger TA, Ständer S (2008) Chronic pruritus: targets, mechanisms and future therapies. Drug News Perspect 21:541–551PubMedGoogle Scholar
  64. Reich A, Orda A, Wiśnicka B, Szepietowski JC (2007) Plasma neuropeptides and perception of pruritus in psoriasis. Acta Derm Venereol 87:299–304PubMedCrossRefGoogle Scholar
  65. Remröd C, Lonne-Rahm S, Nordlind K (2007) Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus. Arch Dermatol Res 299:85–91PubMedCrossRefGoogle Scholar
  66. Ruhlmann CH, Herrstedt J (2011) Safety evaluation of aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Expert Opin Drug Saf 10:449–462PubMedCrossRefGoogle Scholar
  67. Saeed AW, Ribeiro-da-Silva A (2013) De novo expression of neurokinin-1 receptors by spinoparabrachial lamina I pyramidal neurons following a peripheral nerve lesion. J Comp Neurol 521:1915–1928PubMedCrossRefGoogle Scholar
  68. Sahbaie P, Shi X, Guo TZ, Qiao Y, Yeomans DC, Kingery WS, Clark JD (2009) Role of substance P signaling in enhanced nociceptive sensitization and local cytokine production after incision. Pain 145:341–349PubMedCentralPubMedCrossRefGoogle Scholar
  69. Salomon J, Baran E (2008) The role of selected neuropeptides in pathogenesis of atopic dermatitis. J Eur Acad Dermatol Veneoreol 22:223–228Google Scholar
  70. Santini D, Vincenzi B, Guida FM, Imperatori M, Schiavon G, Venditti O, Frezza AM, Berti P, Tonini G (2012) Aprepitant for management of severe pruritus related to biological cancer treatments: a pilot study. Lancet Oncol 13:1020–1024PubMedCrossRefGoogle Scholar
  71. Scholzen T, Armstrong CA, Bunnett NW, Luger TA, Olerud JE, Ansel JC (1998) Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. Exp Dermatol 272:81–96CrossRefGoogle Scholar
  72. Scholzen TE, Ständer S, Riemann H, Brzoska T, Luger TA (2003) Modulation of cutaneous inflammation by angiotensin-converting enzyme. J Immunol 170:3866–3873PubMedCrossRefGoogle Scholar
  73. Scholzen TE, Steinhoff M, Sindrilaru A, Schwarz A, Bunnett NW, Luger TA, Armstrong CA, Ansel JC (2004) Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage. FASEB J 18:1007–1009PubMedGoogle Scholar
  74. Serra J, Campero M, Bostock H, Ochoa J (2004) Two types of C nociceptors in human skin and their behavior in areas of capsaicin-induced secondary hyperalgesia. J Neurophysiol 91:2770–2781PubMedCrossRefGoogle Scholar
  75. Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blum RA (2004) Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol 44:215–223PubMedCrossRefGoogle Scholar
  76. Siepmann D, Weishaupt C, Luger TA, Ständer S (2011) Evaluation of the German guideline for chronic pruritus: results of a retrospective study on 385 patients. Dermatology 223:374–380PubMedCrossRefGoogle Scholar
  77. Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC (1999) Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders. Brain Behav Immun 13:225–239PubMedCrossRefGoogle Scholar
  78. Southwell BR, Seybold VS, Woodman HL, Jenkinson KM, Furness JB (1998) Quantitation of neurokinin 1 receptor internalization and recycling in guinea-pig myenteric neurons. Neuroscience 87:925–931PubMedCrossRefGoogle Scholar
  79. Ständer S, Weisshaar E (2012) Medical treatment of pruritus. Expert Opin Emerg Drugs 17:335–345PubMedCrossRefGoogle Scholar
  80. Ständer S, Weisshaar E, Mettang T, Szepietowski JC, Carstens E, Ikoma A, Bergasa NV, Gieler U, Misery L, Wallengren J, Darsow U, Streit M, Metze D, Luger TA, Greaves MW, Schmelz M, Yosipovitch G, Bernhard JD (2007) Clinical classification of itch: a position paper of the International Forum for the Study of Itch. Acta Derm Venereol 87:291–294PubMedCrossRefGoogle Scholar
  81. Ständer S, Siepmann D, Luger TA (2009) Targeting the neurokinin receptor 1 as a new antipruritic strategy: results of a case series with aprepitant. Acta Derm Venereol 89:717CrossRefGoogle Scholar
  82. Ständer S, Siepmann D, Herrgott I, Sunderkötter C, Luger TA (2010) Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One 5:e10968PubMedCentralPubMedCrossRefGoogle Scholar
  83. Ständer S, Blome C, Breil B, Bruland P, Darsow U, Dugas M, Evers A, Fritz F, Metz M, Phan NQ, Raap U, Reich A, Schneider G, Steinke S, Szepietowski J, Weisshaar E, Augustin M (2012a) Assessment of pruritus—current standards and implications for clinical practice: consensus paper of the Action Group Pruritus Parameter of the National Working Group on Pruritus Research (AGP). Hautarzt 63:521–531PubMedCrossRefGoogle Scholar
  84. Ständer S, Darsow U, Mettang T, Gieler U, Maurer M, Ständer H, Beuers U, Niemeier V, Gollnick H, Vogelgsang M, Weisshaar E (2012b) S2k guideline–Chronic Pruritus. J Dtsch Dermatol Ges 4:S1–S27CrossRefGoogle Scholar
  85. Takeda M, Takahashi M, Matsumoto S (2012) Suppression of neurokinin-1 receptor in trigeminal ganglia attenuates central sensitization following inflammation. J Peripher Nerv Syst 17:169–181PubMedCrossRefGoogle Scholar
  86. Tanaka T, Danno K, Ikai K, Imamura S (1988) Effects of substance P and substance K on the growth of cultured keratinocytes. J Invest Dermatol 90:399–401PubMedCrossRefGoogle Scholar
  87. Tebas P, Tuluc F, Barrett JS, Wagner W, Kim D, Zhao H, Gonin R, Korelitz J, Douglas SD (2011) A randomized, placebo controlled, double masked phase IB study evaluating the safety and antiviral activity of aprepitant, a neurokinin-1 receptor antagonist in HIV-1 infected adults. PLoS One 6:e24180PubMedCentralPubMedCrossRefGoogle Scholar
  88. Teodoro FC, Tronco Júnior MF, Zampronio AR, Martini AC, Rae GA, Chichorro JG (2013) Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models. Neuropeptides 47:199–206PubMedCrossRefGoogle Scholar
  89. Thomsen JS, Sonne M, Benfeldt E, Jensen SB, Serup J, Menné T (2002) Experimental itch in sodium lauryl sulphate-inflamed and normal skin in humans: a randomized, double-blind, placebo-controlled study of histamine and other inducers of itch. Br J Dermatol 146:792–800PubMedCrossRefGoogle Scholar
  90. Torres T, Fernandes I, Selores M, Alves R, Lima M (2012) Aprepitant: evidence of its effectiveness in patients with refractory pruritus continues. J Am Acad Dermatol 66:e14–e15PubMedCrossRefGoogle Scholar
  91. Toyoda M, Nakamura M, Makino T, Hino T, Kagoura M, Morohashi M (2002) Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis. Br J Dermatol 147:71–79PubMedCrossRefGoogle Scholar
  92. Trivedi M, Bergasa NV (2010) Serum concentrations of substance P in cholestasis. Ann Hepatol 9:177–180PubMedGoogle Scholar
  93. Vincenzi B, Fratto ME, Santini D, Tonini G (2010a) Aprepitant against pruritus in patients with solid tumours. Support Care Cancer 18:1229–1230PubMedCrossRefGoogle Scholar
  94. Vincenzi B, Tonini G, Santini D (2010b) Aprepitant for erlotinib-induced pruritus. N Engl J Med 363:397–398PubMedCrossRefGoogle Scholar
  95. Weidner C, Klede M, Rukwied R, Lischetzki G, Neisius U, Skov PS, Petersen LJ, Schmelz M (2000) Acute effects of substance P and calcitonin gene-related peptide in human skin—a microdialysis study. J Invest Dermatol 115:1015–1020PubMedCrossRefGoogle Scholar
  96. Weisshaar E, Dalgard F (2009) Epidemiology of itch: adding to the burden of skin morbidity. Acta Derm Venereol 89:339–350PubMedCrossRefGoogle Scholar
  97. Weisshaar E, Szepietowski JC, Darsow U, Misery L, Wallengren J, Mettang T, Gieler U, Lotti T, Lambert J, Maisel P, Streit M, Greaves MW, Carmichael AJ, Tschachler E, Ring J, Ständer S (2012) European guideline on chronic pruritus. Acta Derm Venereol 92:563–581PubMedCrossRefGoogle Scholar
  98. Wong BJ, Minson CT (2011) Altered thermal hyperaemia in human skin by prior desensitization of neurokinin-1 receptors. Exp Physiol 96:599–609PubMedCentralPubMedCrossRefGoogle Scholar
  99. Yamaoka J, Kawana S (2007) Rapid changes in substance P signaling and neutral endopeptidase induced by skin-scratching stimulation in mice. J Dermatol Sci 48:123–32PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of DermatologyCompetence Center Chronic Pruritus, University Hospital of MünsterMünsterGermany
  2. 2.University Hospital of MünsterMünsterGermany

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