Molecular signaling and targets from itch: lessons for cough

Cough

Xingzhong Dong¹  Pamela Colleen LaVinka² 

[1] Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA;The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, 725 N Wolfe Street, Baltimore, MD, 21205, USA

关键词: Inflammation;    GPCRs;    TRPs;    Mast cells;    A-fibers;    C-fibers;    Airway;    Skin;    Cough;    Itch;   

Others  :  809256
DOI  :  10.1186/1745-9974-9-8

 received in 2012-11-16, accepted in 2013-02-08,  发布年份 2013

【 摘 要 】

Itch is described as an unpleasant sensation that elicits the desire to scratch, which results in the removal of the irritant from the skin. The cough reflex also results from irritation, with the purpose of removing said irritant from the airway. Could cough then be similar to itch? Anatomically, both pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. Both cough and itch also involve mast cells and their mediators, which are released upon degranulation. This common inflammation and interaction with mast cells are involved in the development of chronic conditions of itch and cough. In this review, we examine the anatomy and molecular mechanisms of itch and compare them to known mechanisms for cough. Highlighting the common aspects of itch and cough could lead to new thoughts and perspectives in both fields.

【 授权许可】

   
2013 LaVinka and Dong; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Yosipovitch G, Duque MI, Fast K, Dawn AG, Coghill RC: Scratching and noxious heat stimuli inhibit itch in humans: a psychophysical study. Br J Dermatol 2007, 156(4):629-634.
• [2]Zylka MJ, Dong X, Southwell AL, Anderson DJ: Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family. Proc Natl Acad Sci USA 2003, 100(17):10043-10048.
• [3]Widdicombe JG: Afferent receptors in the airways and cough. Respir Physiol 1998, 114(1):5-15.
• [4]Nasra J, Belvisi MG: Modulation of sensory nerve function and the cough reflex: understanding disease pathogenesis. Pharmacol Ther 2009, 124(3):354-375.
• [5]Karlsson JA, Sant’Ambrogio G, Widdicombe J: Afferent neural pathways in cough and reflex bronchoconstriction. J Appl Physiol 1988, 65(3):1007-1023.
• [6]Paus R, Schmelz M, Biro T, Steinhoff M: Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest 2006, 116(5):1174-1186.
• [7]Undem BJ, Chuaychoo B, Lee MG, Weinreich D, Myers AC, Kollarik M: Subtypes of vagal afferent C-fibres in guinea-pig lungs. J Physiol 2004, 556(Pt 3):905-917.
• [8]Brozmanova M, Ru F, Surdenikova L, Mazurova L, Taylor-Clark T, Kollarik M: Preferential activation of the vagal nodose nociceptive subtype by TRPA1 agonists in the guinea pig esophagus. Neurogastroenterol Motil 2011, 23(10):e437-45.
• [9]Graham DT, Goodell H, WOLFF HG: Neural mechanisms involved in itch, itchy skin, and tickle sensations. J Clin Invest 1951, 30(1):37-49.
• [10]Shelley WB, Arthur RP: The neurohistology and neurophysiology of the itch sensation in man. AMA Arch Derm 1957, 76(3):296-323.
• [11]Ringkamp M, Schepers RJ, Shimada SG, Johanek LM, Hartke TV, Borzan J, Shim B, LaMotte RH, Meyer RA: A role for nociceptive, myelinated nerve fibers in itch sensation. J Neurosci 2011, 31(42):14841-14849.
• [12]Lieu T, Undem BJ: Neuroplasticity in vagal afferent neurons involved in cough. Pulm Pharmacol Ther 2011, 24(3):276-279.
• [13]Canning BJ, Mori N, Mazzone SB: Vagal afferent nerves regulating the cough reflex. Respir Physiol Neurobiol 2006, 152(3):223-242.
• [14]Tatar M, Sant’Ambrogio G, Sant’Ambrogio FB: Laryngeal and tracheobronchial cough in anesthetized dogs. J Appl Physiol 1994, 76(6):2672-2679.
• [15]Fox AJ, Barnes PJ, Dray A: Stimulation of guinea-pig tracheal afferent fibres by non-isosmotic and low-chloride stimuli and the effect of frusemide. J Physiol 1995, 482 (Pt 1)(Pt 1):179-187.
• [16]Fox AJ, Barnes PJ, Urban L, Dray A: An in vitro study of the properties of single vagal afferents innervating guinea-pig airways. J Physiol 1993, 469:21-35.
• [17]Widdicombe JG: Receptors in the trachea and bronchi of the cat. J Physiol 1954, 123(1):71-104.
• [18]Widdicombe J: Functional morphology and physiology of pulmonary rapidly adapting receptors (RARs). Anat Rec A Discov Mol Cell Evol Biol 2003, 270(1):2-10.
• [19]Schelegle ES: Functional morphology and physiology of slowly adapting pulmonary stretch receptors. Anat Rec A Discov Mol Cell Evol Biol 2003, 270(1):11-16.
• [20]Canning BJ, Chou YL: Cough sensors. I. Physiological and pharmacological properties of the afferent nerves regulating cough. Handb Exp Pharmacol 2009, 187(187):23-47.
• [21]Canning BJ: Functional implications of the multiple afferent pathways regulating cough. Pulm Pharmacol Ther 2011, 24(3):295-299.
• [22]Canning BJ, Mazzone SB, Meeker SN, Mori N, Reynolds SM, Undem BJ: Identification of the tracheal and laryngeal afferent neurones mediating cough in anaesthetized guinea-pigs. J Physiol 2004, 557(Pt 2):543-558.
• [23]Kwong K, Carr MJ, Gibbard A, Savage TJ, Singh K, Jing J, Meeker S, Undem BJ: Voltage-gated sodium channels in nociceptive versus non-nociceptive nodose vagal sensory neurons innervating guinea pig lungs. J Physiol 2008, 586(5):1321-1336.
• [24]Namer B, Carr R, Johanek LM, Schmelz M, Handwerker HO, Ringkamp M: Separate peripheral pathways for pruritus in man. J Neurophysiol 2008, 100(4):2062-2069.
• [25]Sant’Ambrogio G, Widdicombe J: Reflexes from airway rapidly adapting receptors. Respir Physiol 2001, 125(1–2):33-45.
• [26]Winkelmann RK: Some sensory nerve endings in the skin; preliminary report on the morphology of cutaneous sensation. AMA Arch Derm 1955, 71(3):373-378.
• [27]Schmelz M, Schmidt R, Bickel A, Handwerker HO, Torebjork HE: Specific C-receptors for itch in human skin. J Neurosci 1997, 17(20):8003-8008.
• [28]Toth-Kasa I, Jancso G, Bognar A, Husz S, Obal F Jr: Capsaicin prevents histamine-induced itching. Int J Clin Pharmacol Res 1986, 6(2):163-169.
• [29]Ma C, Nie H, Gu Q, Sikand P, Lamotte RH: In vivo responses of cutaneous C-mechanosensitive neurons in mouse to punctate chemical stimuli that elicit itch and nociceptive sensations in humans. J Neurophysiol 2012, 107(1):357-363.
• [30]Mazzone SB, Undem BJ: Cough sensors. V. Pharmacological modulation of cough sensors. Handb Exp Pharmacol 2009, 187(187):99-127.
• [31]Forsberg K, Karlsson JA, Theodorsson E, Lundberg JM, Persson CG: Cough and bronchoconstriction mediated by capsaicin-sensitive sensory neurons in the guinea-pig. Pulm Pharmacol 1988, 1(1):33-39.
• [32]Ricco MM, Kummer W, Biglari B, Myers AC, Undem BJ: Interganglionic segregation of distinct vagal afferent fibre phenotypes in guinea-pig airways. J Physiol 1996, 496 ( Pt 2)(Pt 2):521-530.
• [33]Palecek F, Sant’Ambrogio G, Sant’Ambrogio FB, Mathew OP: Reflex responses to capsaicin: intravenous, aerosol, and intratracheal administration. J Appl Physiol 1989, 67(4):1428-1437.
• [34]Lee LY, Pisarri TE: Afferent properties and reflex functions of bronchopulmonary C-fibers. Respir Physiol 2001, 125(1–2):47-65.
• [35]Hunter DD, Undem BJ: Identification and substance P content of vagal afferent neurons innervating the epithelium of the guinea pig trachea. Am J Respir Crit Care Med 1999, 159(6):1943-1948.
• [36]Kummer W, Fischer A, Kurkowski R, Heym C: The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry. Neuroscience 1992, 49(3):715-737.
• [37]Nassenstein C, Taylor-Clark TE, Myers AC, Ru F, Nandigama R, Bettner W, Undem BJ: Phenotypic distinctions between neural crest and placodal derived vagal C-fibres in mouse lungs. J Physiol 2010, 588(Pt 23):4769-4783.
• [38]Lee LY, Kwong K, Lin YS, Gu Q: Hypersensitivity of bronchopulmonary C-fibers induced by airway mucosal inflammation: cellular mechanisms. Pulm Pharmacol Ther 2002, 15(3):199-204.
• [39]Joad JP, Kott KS, Bonham AC: Nitric oxide contributes to substance P-induced increases in lung rapidly adapting receptor activity in guinea-pigs. J Physiol 1997, 503 ( Pt 3)(Pt 3):635-643.
• [40]Mazzone SB, Mori N, Canning BJ: Synergistic interactions between airway afferent nerve subtypes regulating the cough reflex in guinea-pigs. J Physiol 2005, 569(Pt 2):559-573.
• [41]Ross SE: Pain and itch: insights into the neural circuits of aversive somatosensation in health and disease. Curr Opin Neurobiol 2011, 21(6):880-887.
• [42]Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D: The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997, 389(6653):816-824.
• [43]Sikand P, Shimada SG, Green BG, LaMotte RH: Similar itch and nociceptive sensations evoked by punctate cutaneous application of capsaicin, histamine and cowhage. Pain 2009, 144(1–2):66-75.
• [44]Shim WS, Tak MH, Lee MH, Kim M, Kim M, Koo JY, Lee CH, Kim M, Oh U: TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase. J Neurosci 2007, 27(9):2331-2337.
• [45]Patel KN, Liu Q, Meeker S, Undem BJ, Dong X: Pirt, a TRPV1 modulator, is required for histamine-dependent and -independent itch. PLoS One 2011, 6(5):e20559.
• [46]Imamachi N, Park GH, Lee H, Anderson DJ, Simon MI, Basbaum AI, Han SK: TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proc Natl Acad Sci USA 2009, 106(27):11330-11335.
• [47]Woo DH, Jung SJ, Zhu MH, Park CK, Kim YH, Oh SB, Lee CJ: Direct activation of transient receptor potential vanilloid 1(TRPV1) by diacylglycerol (DAG). Mol Pain 2008, 4:42. BioMed Central Full Text
• [48]Yun JW, Seo JA, Jang WH, Koh HJ, Bae IH, Park YH, Lim KM: Antipruritic effects of TRPV1 antagonist in murine atopic dermatitis and itching models. J Invest Dermatol 2011, 131(7):1576-1579.
• [49]Hutter MM, Wick EC, Day AL, Maa J, Zerega EC, Richmond AC, Jordan TH, Grady EF, Mulvihill SJ, Bunnett NW, Kirkwood KS: Transient receptor potential vanilloid (TRPV-1) promotes neurogenic inflammation in the pancreas via activation of the neurokinin-1 receptor (NK-1R). Pancreas 2005, 30(3):260-265.
• [50]Grace M, Birrell MA, Dubuis E, Maher SA, Belvisi MG: Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin. Thorax 2012, 67(10):891-900.
• [51]Ichikawa H, Sugimoto T: The co-expression of VR1 and VRL-1 in the rat vagal sensory ganglia. Brain Res 2003, 980(2):293-296.
• [52]Watanabe N, Horie S, Michael GJ, Keir S, Spina D, Page CP, Priestley JV: Immunohistochemical co-localization of transient receptor potential vanilloid (TRPV)1 and sensory neuropeptides in the guinea-pig respiratory system. Neuroscience 2006, 141(3):1533-1543.
• [53]Groneberg DA, Niimi A, Dinh QT, Cosio B, Hew M, Fischer A, Chung KF: Increased expression of transient receptor potential vanilloid-1 in airway nerves of chronic cough. Am J Respir Crit Care Med 2004, 170(12):1276-1280.
• [54]Laude EA, Higgins KS, Morice AH: A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man. Pulm Pharmacol 1993, 6(3):171-175.
• [55]Lalloo UG, Fox AJ, Belvisi MG, Chung KF, Barnes PJ: Capsazepine inhibits cough induced by capsaicin and citric acid but not by hypertonic saline in guinea pigs. J Appl Physiol 1995, 79(4):1082-1087.
• [56]Bolser DC, Aziz SM, Chapman RW: Ruthenium red decreases capsaicin and citric acid-induced cough in guinea pigs. Neurosci Lett 1991, 126(2):131-133.
• [57]Jia Y, McLeod RL, Wang X, Parra LE, Egan RW, Hey JA: Anandamide induces cough in conscious guinea-pigs through VR1 receptors. Br J Pharmacol 2002, 137(6):831-836.
• [58]Hinman A, Chuang HH, Bautista DM, Julius D: TRP channel activation by reversible covalent modification. Proc Natl Acad Sci USA 2006, 103(51):19564-19568.
• [59]Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A: Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 2007, 445(7127):541-545.
• [60]Liu Q, Tang Z, Surdenikova L, Kim S, Patel KN, Kim A, Ru F, Guan Y, Weng HJ, Geng Y, Undem BJ, Kollarik M, Chen ZF, Anderson DJ, Dong X: Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell 2009, 139(7):1353-1365.
• [61]Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, Bautista DM: TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci 2011, 14(5):595-602.
• [62]Liu T, Ji RR: Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice. Neurosci Bull 2012, 28(2):145-154.
• [63]Bickers DR, Athar M: Oxidative stress in the pathogenesis of skin disease. J Invest Dermatol 2006, 126(12):2565-2575.
• [64]Nassenstein C, Kwong K, Taylor-Clark T, Kollarik M, Macglashan DM, Braun A, Undem BJ: Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs. J Physiol 2008, 586(6):1595-1604.
• [65]Bessac BF, Sivula M, Von Hehn CA, Escalera J, Cohn L, Jordt SE: TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest 2008, 118(5):1899-1910.
• [66]Belvisi MG, Stretton CD, Barnes PJ: Bombesin-induced bronchoconstriction in the guinea pig: mode of action. J Pharmacol Exp Ther 1991, 258(1):36-41.
• [67]Birrell MA, Belvisi MG, Grace M, Sadofsky L, Faruqi S, Hele DJ, Maher SA, Freund-Michel V, Morice AH: TRPA1 agonists evoke coughing in guinea pig and human volunteers. Am J Respir Crit Care Med 2009, 180(11):1042-1047.
• [68]Brozmanova M, Mazurova L, Ru F, Tatar M, Kollarik M: Comparison of TRPA1-versus TRPV1-mediated cough in guinea pigs. Eur J Pharmacol 2012, 689(1–3):211-218.
• [69]Andre E, Campi B, Materazzi S, Trevisani M, Amadesi S, Massi D, Creminon C, Vaksman N, Nassini R, Civelli M, Baraldi PG, Poole DP, Bunnett NW, Geppetti P, Patacchini R: Cigarette smoke-induced neurogenic inflammation is mediated by alpha, beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest 2008, 118(7):2574-2582.
• [70]Andre E, Gatti R, Trevisani M, Preti D, Baraldi PG, Patacchini R, Geppetti P: Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents. Br J Pharmacol 2009, 158(6):1621-1628.
• [71]Holzer P: Neurogenic vasodilatation and plasma leakage in the skin. Gen Pharmacol 1998, 30(1):5-11.
• [72]Hosogi M, Schmelz M, Miyachi Y, Ikoma A: Bradykinin is a potent pruritogen in atopic dermatitis: a switch from pain to itch. Pain 2006, 126(1–3):16-23.
• [73]Hagermark O, Hokfelt T, Pernow B: Flare and itch induced by substance P in human skin. J Invest Dermatol 1978, 71(4):233-235.
• [74]Yamaoka J, Kawana S: Rapid changes in substance P signaling and neutral endopeptidase induced by skin-scratching stimulation in mice. J Dermatol Sci 2007, 48(2):123-132.
• [75]Ohmura T, Hayashi T, Satoh Y, Konomi A, Jung B, Satoh H: Involvement of substance P in scratching behaviour in an atopic dermatitis model. Eur J Pharmacol 2004, 491(2–3):191-194.
• [76]Stander S, Siepmann D, Herrgott I, Sunderkotter C, Luger TA: Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One 2010, 5(6):e10968.
• [77]Canning BJ, Reynolds SM, Mazzone SB: Multiple mechanisms of reflex bronchospasm in guinea pigs. J Appl Physiol 2001, 91(6):2642-2653.
• [78]El-Hashim AZ, Amine SA: The role of substance P and bradykinin in the cough reflex and bronchoconstriction in guinea-pigs. Eur J Pharmacol 2005, 513(1–2):125-133.
• [79]Moore KA, Undem BJ, Weinreich D: Antigen inhalation unmasks NK-2 tachykinin receptor-mediated responses in vagal afferents. Am J Respir Crit Care Med 2000, 161(1):232-236.
• [80]Bae YJ, Moon KA, Kim TB, Jang YJ, Lee YS, Park CS, Lee KY, Moon HB, Cho YS: The role of nitrosative stress in the pathogenesis of unexplained chronic cough with cough hypersensitivity. Am J Rhinol Allergy 2012, 26(1):e10-4.
• [81]Otsuka K, Niimi A, Matsumoto H, Ito I, Yamaguchi M, Matsuoka H, Jinnai M, Oguma T, Takeda T, Nakaji H, Chin K, Sasaki K, Aoyama N, Mishima M: Plasma substance P levels in patients with persistent cough. Respiration 2011, 82(5):431-438.
• [82]Liang J, He Y, Ji W: Bradykinin-evoked scratching responses in complete Freund’s adjuvant-inflamed skin through activation of B1 receptor. Exp Biol Med (Maywood) 2012, 237(3):318-326.
• [83]Costa R, Manjavachi MN, Motta EM, Marotta DM, Juliano L, Torres HA, Pesquero JB, Calixto JB: The role of kinin B1 and B2 receptors in the scratching behaviour induced by proteinase-activated receptor-2 agonists in mice. Br J Pharmacol 2010, 159(4):888-897.
• [84]Thestrup-Pedersen K: Adverse reactions in the skin from anti-hypertensive drugs. Dan Med Bull 1987, 34(Suppl 1):3-5.
• [85]Steckelings UM, Artuc M, Wollschlager T, Wiehstutz S, Henz BM: Angiotensin-converting enzyme inhibitors as inducers of adverse cutaneous reactions. Acta Derm Venereol 2001, 81(5):321-325.
• [86]Baumgarten CR, Lehmkuhl B, Henning R, Brunnee T, Dorow P, Schilling W, Kunkel G: Bradykinin and other inflammatory mediators in BAL-fluid from patients with active pulmonary inflammation. Agents Actions Suppl 1992, 38 ( Pt 3)(Pt 3):475-481.
• [87]Kajekar R, Proud D, Myers AC, Meeker SN, Undem BJ: Characterization of vagal afferent subtypes stimulated by bradykinin in guinea pig trachea. J Pharmacol Exp Ther 1999, 289(2):682-687.
• [88]Fuller RW, Dixon CM, Cuss FM, Barnes PJ: Bradykinin-induced bronchoconstriction in humans. Mode of action. Am Rev Respir Dis 1987, 135(1):176-180.
• [89]Choudry NB, Fuller RW, Pride NB: Sensitivity of the human cough reflex: effect of inflammatory mediators prostaglandin E2, bradykinin, and histamine. Am Rev Respir Dis 1989, 140(1):137-141.
• [90]Krstew E, Jarrott B, Lawrence AJ: Bradykinin B2 receptors in nodose ganglia of rat and human. Eur J Pharmacol 1998, 348(2–3):175-180.
• [91]Fox AJ, Lalloo UG, Belvisi MG, Bernareggi M, Chung KF, Barnes PJ: Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough. Nat Med 1996, 2(7):814-817.
• [92]Kang DS, Leeb-Lundberg LM: Negative and positive regulatory epitopes in the C-terminal domains of the human B1 and B2 bradykinin receptor subtypes determine receptor coupling efficacy to G(q/11)-mediated [correction of G(9/11)-mediated] phospholipase Cbeta activity. Mol Pharmacol 2002, 62(2):281-288.
• [93]Lee MG, Kollarik M, Chuaychoo B, Undem BJ: Ionotropic and metabotropic receptor mediated airway sensory nerve activation. Pulm Pharmacol Ther 2004, 17(6):355-360.
• [94]Botchkarev VA, Eichmuller S, Peters EM, Pietsch P, Johansson O, Maurer M, Paus R: A simple immunofluorescence technique for simultaneous visualization of mast cells and nerve fibers reveals selectivity and hair cycle–dependent changes in mast cell–nerve fiber contacts in murine skin. Arch Dermatol Res 1997, 289(5):292-302.
• [95]Boulet LP, Milot J, Boutet M, St Georges F, Laviolette M: Airway inflammation in nonasthmatic subjects with chronic cough. Am J Respir Crit Care Med 1994, 149(2 Pt 1):482-489.
• [96]McGarvey LP, Forsythe P, Heaney LG, MacMahon J, Ennis M: Bronchoalveolar lavage findings in patients with chronic nonproductive cough. Eur Respir J 1999, 13(1):59-65.
• [97]Rao KN, Brown MA: Mast cells: multifaceted immune cells with diverse roles in health and disease. Ann N Y Acad Sci 2008, 1143:83-104.
• [98]Simone DA, Ngeow JY, Whitehouse J, Becerra-Cabal L, Putterman GJ, LaMotte RH: The magnitude and duration of itch produced by intracutaneous injections of histamine. Somatosens Res 1987, 5(2):81-92.
• [99]Sikand P, Shimada SG, Green BG, LaMotte RH: Sensory responses to injection and punctate application of capsaicin and histamine to the skin. Pain 2011, 152(11):2485-2494.
• [100]Akiyama T, Merrill AW, Zanotto K, Carstens MI, Carstens E: Scratching behavior and Fos expression in superficial dorsal horn elicited by protease-activated receptor agonists and other itch mediators in mice. J Pharmacol Exp Ther 2009, 329(3):945-951.
• [101]Andrew D, Craig AD: Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 2001, 4(1):72-77.
• [102]Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol 2011, 128(6):1139-1150. e4
• [103]Riley JF, West GB: The presence of histamine in tissue mast cells. J Physiol 1953, 120(4):528-537.
• [104]Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, Schunack W, Levi R, Haas HL: International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev 1997, 49(3):253-278.
• [105]Davies MG, Greaves MW: Sensory responses of human skin to synthetic histamine analogues and histamine. Br J Clin Pharmacol 1980, 9(5):461-465.
• [106]Bakker RA, Timmerman H, Leurs R: Histamine receptors: specific ligands, receptor biochemistry, and signal transduction. Clin Allergy Immunol 2002, 17:27-64.
• [107]Han SK, Mancino V, Simon MI: Phospholipase Cbeta 3 mediates the scratching response activated by the histamine H1 receptor on C-fiber nociceptive neurons. Neuron 2006, 52(4):691-703.
• [108]Kim BM, Lee SH, Shim WS, Oh U: Histamine-induced Ca(2+) influx via the PLA(2)/lipoxygenase/TRPV1 pathway in rat sensory neurons. Neurosci Lett 2004, 361(1–3):159-162.
• [109]Ikoma A, Rukwied R, Stander S, Steinhoff M, Miyachi Y, Schmelz M: Neuronal sensitization for histamine-induced itch in lesional skin of patients with atopic dermatitis. Arch Dermatol 2003, 139(11):1455-1458.
• [110]Bell JK, McQueen DS, Rees JL: Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice. Br J Pharmacol 2004, 142(2):374-380.
• [111]Cowden JM, Zhang M, Dunford PJ, Thurmond RL: The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol 2010, 130(4):1023-1033.
• [112]Dunford PJ, Williams KN, Desai PJ, Karlsson L, McQueen D, Thurmond RL: Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J Allergy Clin Immunol 2007, 119(1):176-183.
• [113]Undem BJ, Weinreich D: Electrophysiological properties and chemosensitivity of guinea pig nodose ganglion neurons in vitro. J Auton Nerv Syst 1993, 44(1):17-33.
• [114]Lee LY, Morton RF: Histamine enhances vagal pulmonary C-fiber responses to capsaicin and lung inflation. Respir Physiol 1993, 93(1):83-96.
• [115]Lai YL, Lin TY: Mast cells in citric acid-induced cough of guinea pigs. Toxicol Appl Pharmacol 2005, 202(1):18-24.
• [116]Birring SS, Parker D, Brightling CE, Bradding P, Wardlaw AJ, Pavord ID: Induced sputum inflammatory mediator concentrations in chronic cough. Am J Respir Crit Care Med 2004, 169(1):15-19.
• [117]Brightling CE, Ward R, Woltmann G, Bradding P, Sheller JR, Dworski R, Pavord ID: Induced sputum inflammatory mediator concentrations in eosinophilic bronchitis and asthma. Am J Respir Crit Care Med 2000, 162(3 Pt 1):878-882.
• [118]Tanaka S, Hirata K, Kurihara N, Yoshikawa J, Takeda T: Effect of loratadine, an H1 antihistamine, on induced cough in non-asthmatic patients with chronic cough. Thorax 1996, 51(8):810-814.
• [119]Weigand LA, Myers AC, Meeker S, Undem BJ: Mast cell-cholinergic nerve interaction in mouse airways. J Physiol 2009, 587(Pt 13):3355-3362.
• [120]Kushnir-Sukhov NM, Brown JM, Wu Y, Kirshenbaum A, Metcalfe DD: Human mast cells are capable of serotonin synthesis and release. J Allergy Clin Immunol 2007, 119(2):498-499.
• [121]Konig P, Krain B, Krasteva G, Kummer W: Serotonin increases cilia-driven particle transport via an acetylcholine-independent pathway in the mouse trachea. PLoS One 2009, 4(3):e4938.
• [122]Brouns I, Oztay F, Pintelon I, De Proost I, Lembrechts R, Timmermans JP, Adriaensen D: Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs. Histochem Cell Biol 2009, 131(1):55-74.
• [123]Klein A, Carstens MI, Carstens E: Facial injections of pruritogens or algogens elicit distinct behavior responses in rats and excite overlapping populations of primary sensory and trigeminal subnucleus caudalis neurons. J Neurophysiol 2011, 106(3):1078-1088.
• [124]Hachisuka J, Furue H, Furue M, Yoshimura M: Responsiveness of C neurons in rat dorsal root ganglion to 5-hydroxytryptamine-induced pruritic stimuli in vivo. J Neurophysiol 2010, 104(1):271-279.
• [125]Akiyama T, Carstens MI, Carstens E: Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch. Pain 2010, 151(2):378-383.
• [126]Huang J, Li G, Xiang J, Yin D, Chi R: Immunohistochemical study of serotonin in lesions of psoriasis. Int J Dermatol 2004, 43(6):408-411.
• [127]Huang J, Li G, Xiang J, Yin D, Chi R: Immunohistochemical study of serotonin in lesions of chronic eczema. Int J Dermatol 2004, 43(10):723-726.
• [128]Schmelz M, Schmidt R, Weidner C, Hilliges M, Torebjork HE, Handwerker HO: Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens. J Neurophysiol 2003, 89(5):2441-2448.
• [129]Yamaguchi T, Nagasawa T, Satoh M, Kuraishi Y: Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice. Neurosci Res 1999, 35(2):77-83.
• [130]Bonnet F, Marret E: Anaesthesia outside the operating room: conflicting strategies? Curr Opin Anaesthesiol 2008, 21(4):478-479.
• [131]Coleridge HM, Coleridge JC, Schultz HD: Afferent pathways involved in reflex regulation of airway smooth muscle. Pharmacol Ther 1989, 42(1):1-63.
• [132]Coleridge HM, Coleridge JC: Impulse activity in afferent vagal C-fibres with endings in the intrapulmonary airways of dogs. Respir Physiol 1977, 29(2):125-142.
• [133]Peters JA, Malone HM, Lambert JJ: An electrophysiological investigation of the properties of 5-HT3 receptors of rabbit nodose ganglion neurones in culture. Br J Pharmacol 1993, 110(2):665-676.
• [134]Malone HM, Peters JA, Lambert JJ: Physiological and pharmacological properties of 5-HT3 receptors–a patch clamp-study. Neuropeptides 1991, 19(Suppl):25-30.
• [135]Higashi H: Pharmacological aspects of visceral sensory receptors. Prog Brain Res 1986, 67:149-162.
• [136]Chuaychoo B, Lee MG, Kollarik M, Undem BJ: Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs. Pulm Pharmacol Ther 2005, 18(4):269-276.
• [137]Potenzieri C, Meeker S, Undem BJ: Activation of mouse bronchopulmonary C-fibres by serotonin and allergen-ovalbumin challenge. J Physiol 2012, 590(Pt 21):5449-5459.
• [138]Ossovskaya VS, Bunnett NW: Protease-activated receptors: contribution to physiology and disease. Physiol Rev 2004, 84(2):579-621.
• [139]Hollenberg MD, Compton SJ: International Union of Pharmacology. XXVIII. Proteinase-activated receptors. Pharmacol Rev 2002, 54(2):203-217.
• [140]Nystedt S, Emilsson K, Wahlestedt C, Sundelin J: Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci USA 1994, 91(20):9208-9212.
• [141]Shimada SG, Shimada KA, Collins JG: Scratching behavior in mice induced by the proteinase-activated receptor-2 agonist, SLIGRL-NH2. Eur J Pharmacol 2006, 530(3):281-283.
• [142]Sun YG, Chen ZF: A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature 2007, 448(7154):700-703.
• [143]Zhu Y, Wang XR, Peng C, Xu JG, Liu YX, Wu L, Zhu QG, Liu JY, Li FQ, Pan YH, You BM, Hu JH: Induction of leukotriene B(4) and prostaglandin E(2) release from keratinocytes by protease-activated receptor-2-activating peptide in ICR mice. Int Immunopharmacol 2009, 9(11):1332-1336.
• [144]Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, Trevisani M, Hollenberg MD, Wallace JL, Caughey GH, Mitchell SE, Williams LM, Geppetti P, Mayer EA, Bunnett NW: Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med 2000, 6(2):151-158.
• [145]Costa R, Marotta DM, Manjavachi MN, Fernandes ES, Lima-Garcia JF, Paszcuk AF, Quintao NL, Juliano L, Brain SD, Calixto JB: Evidence for the role of neurogenic inflammation components in trypsin-elicited scratching behaviour in mice. Br J Pharmacol 2008, 154(5):1094-1103.
• [146]Steinhoff M, Neisius U, Ikoma A, Fartasch M, Heyer G, Skov PS, Luger TA, Schmelz M: Proteinase-activated receptor-2 mediates itch: a novel pathway for pruritus in human skin. J Neurosci 2003, 23(15):6176-6180.
• [147]Grant AD, Cottrell GS, Amadesi S, Trevisani M, Nicoletti P, Materazzi S, Altier C, Cenac N, Zamponi GW, Bautista-Cruz F, Lopez CB, Joseph EK, Levine JD, Liedtke W, Vanner S, Vergnolle N, Geppetti P, Bunnett NW: Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol 2007, 578(Pt 3):715-733.
• [148]Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, Kobayashi K, Obata K, Yamanaka H, Noguchi K: Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest 2007, 117(7):1979-1987.
• [149]Reddy VB, Iuga AO, Shimada SG, LaMotte RH, Lerner EA: Cowhage-evoked itch is mediated by a novel cysteine protease: a ligand of protease-activated receptors. J Neurosci 2008, 28(17):4331-4335.
• [150]Ricciardolo FL, Steinhoff M, Amadesi S, Guerrini R, Tognetto M, Trevisani M, Creminon C, Bertrand C, Bunnett NW, Fabbri LM, Salvadori S, Geppetti P: Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways. Am J Respir Crit Care Med 2000, 161(5):1672-1680.
• [151]Schmidlin F, Amadesi S, Dabbagh K, Lewis DE, Knott P, Bunnett NW, Gater PR, Geppetti P, Bertrand C, Stevens ME: Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol 2002, 169(9):5315-5321.
• [152]Miotto D, Hollenberg MD, Bunnett NW, Papi A, Braccioni F, Boschetto P, Rea F, Zuin A, Geppetti P, Saetta M, Maestrelli P, Fabbri LM, Mapp CE: Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers. Thorax 2002, 57(2):146-151.
• [153]Cocks TM, Fong B, Chow JM, Anderson GP, Frauman AG, Goldie RG, Henry PJ, Carr MJ, Hamilton JR, Moffatt JD: A protective role for protease-activated receptors in the airways. Nature 1999, 398(6723):156-160.
• [154]Costello JF, Dunlop LS, Gardiner PJ: Characteristics of prostaglandin induced cough in man. Br J Clin Pharmacol 1985, 20(4):355-359.
• [155]Carr MJ, Schechter NM, Undem BJ: Trypsin-induced, neurokinin-mediated contraction of guinea pig bronchus. Am J Respir Crit Care Med 2000, 162(5):1662-1667.
• [156]Gatti R, Andre E, Amadesi S, Dinh TQ, Fischer A, Bunnett NW, Harrison S, Geppetti P, Trevisani M: Protease-activated receptor-2 activation exaggerates TRPV1-mediated cough in guinea pigs. J Appl Physiol 2006, 101(2):506-511.
• [157]Amadesi S, Nie J, Vergnolle N, Cottrell GS, Grady EF, Trevisani M, Manni C, Geppetti P, McRoberts JA, Ennes H, Davis JB, Mayer EA, Bunnett NW: Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neurosci 2004, 24(18):4300-4312.
• [158]Liu Q, Weng HJ, Patel KN, Tang Z, Bai H, Steinhoff M, Dong X: The distinct roles of two GPCRs, MrgprC11 and PAR2, in itch and hyperalgesia. Sci Signal 2011, 4(181):ra45.
• [159]Sun YG, Zhao ZQ, Meng XL, Yin J, Liu XY, Chen ZF: Cellular basis of itch sensation. Science 2009, 325(5947):1531-1534.
• [160]Gu Q, Lee LY: Sensitization of pulmonary chemosensitive neurons by bombesin-like peptides in rats. Am J Physiol Lung Cell Mol Physiol 2005, 289(6):L1104-12.
• [161]Kane MA, Toi-Scott M, Johnson GL, Kelley KK, Boose D, Escobedo-Morse A: Bombesin-like peptide receptors in human bronchial epithelial cells. Peptides 1996, 17(1):111-118.
• [162]Schappert SM, Burt CW: Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001–02. Vital Health Stat 2006, 13:1-66.
• [163]Dong X, Han S, Zylka MJ, Simon MI, Anderson DJ: A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 2001, 106(5):619-632.
• [164]Han SK, Dong X, Hwang JI, Zylka MJ, Anderson DJ, Simon MI: Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. Proc Natl Acad Sci USA 2002, 99(23):14740-14745.
• [165]Lembo PM, Grazzini E, Groblewski T, O’Donnell D, Roy MO, Zhang J, Hoffert C, Cao J, Schmidt R, Pelletier M, Labarre M, Gosselin M, Fortin Y, Banville D, Shen SH, Strom P, Payza K, Dray A, Walker P, Ahmad S: Proenkephalin A gene products activate a new family of sensory neuron–specific GPCRs. Nat Neurosci 2002, 5(3):201-209.
• [166]Liu Q, Sikand P, Ma C, Tang Z, Han L, Li Z, Sun S, LaMotte RH, Dong X: Mechanisms of itch evoked by β-alanine. J Neurosci 2012, 32(42):14532-14537.