Abstract
Neurogenic-mediated inflammation may be associated with several inflammatory skin diseases including atopic dermatitis. However, age-dependent differences in neurogenic-mediated skin responses are not fully understood. We compared skin plasma leakage in rats aged 2 and 8 wk, which was induced by topical capsaicin, topical formalin, and intracutaneous substance P, whose effects are mediated via tachykinin NK1 receptors. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. Capsaicin, formalin, and substance P caused a skin response in a dose-dependent manner in both age groups. However, the skin response was much greater in adults than in pups. In addition, the localization of sensory C-fibers and tachykinin NK1 receptors in the skin was investigated by immunofluorescent staining with antisubstance P and antitachykinin NK1 receptor antibodies, respectively. Substance P-immunoreactive nerves were detected throughout the dermis and tachykinin NK1 receptors were mainly detected in blood vessel walls in the dermis in both age groups. However, they were more sparsely distributed in pups. In conclusion, the weak neurogenic-mediated skin inflammation in pups is probably because of immature neural mechanisms associated with skin inflammation such as reduced innervation of sensory C-fibers and low expression of tachykinin NK1 receptors.
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Abbreviations
- TRPV1:
-
Transient receptor potential vanilloid 1
References
Cevikbas F, Steinhoff A, Homey B, Steinhoff M 2007 Neuroimmune interactions in allergic skin diseases. Curr Opin Allergy Clin Immunol 7: 365–373
Holzer P 1998 Neurogenic vasodilatation and plasma leakage in the skin. Gen Pharmacol 30: 5–11
Roosterman D, Goerge T, Schneider SW, Bunnett NW, Steinhoff M 2006 Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev 86: 1309–1379
Fitzgerald M, Gibson S 1984 The postnatal physiological and neurochemical development of peripheral sensory C fibres. Neuroscience 13: 933–944
Schotzinger RJ, Landis SC 1990 Postnatal development of autonomic and sensory innervation of thoracic hairy skin in the rat. A histochemical, immunocytochemical, and radioenzymatic study. Cell Tissue Res 260: 575–587
Gonzales R, Coderre TJ, Sherbourne CD, Levine JD 1991 Postnatal development of neurogenic inflammation in the rat. Neurosci Lett 127: 25–27
Moussaoui SM, Montier F, Carruette A, Blanchard JC, Laduron PM, Garret C 1993 A non-peptide NK1-receptor antagonist, RP 67580, inhibits neurogenic inflammation postsynaptically. Br J Pharmacol 109: 259–264
Damas J, Liegeois JF 1999 The inflammatory reaction induced by formalin in the rat paw. Naunyn Schmiedebergs Arch Pharmacol 359: 220–227
Futamura M, Goto S, Kimura R, Kimoto I, Miyake M, Ito K, Sakamoto T 2009 Differential effects of topically applied formalin and aromatic compounds on neurogenic-mediated microvascular leakage in rat skin. Toxicology 255: 100–106
Lembeck F, Donnerer J, Tsuchiya M, Nagahisa A 1992 The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation. Br J Pharmacol 105: 527–530
Inoue H, Asaka T, Nagata N, Koshihara Y 1997 Mechanism of mustard oil-induced skin inflammation in mice. Eur J Pharmacol 333: 231–240
Matsas R, Fulcher IS, Kenny AJ, Turner AJ 1983 Substance P and [Leu]enkephalin are hydrolyzed by an enzyme in pig caudate synaptic membranes that is identical with the endopeptidase of kidney microvilli. Proc Natl Acad Sci USA 80: 3111–3115
Iwamoto I, Ueki IF, Borson DB, Nadel JA 1989 Neutral endopeptidase modulates tachykinin-induced increase in vascular permeability in guinea pig skin. Int Arch Allergy Appl Immunol 88: 288–293
Hayashi K, Sato H, Kaise T, Ohmori K, Ishii A, Sano J, Karasawa A 2001 Roles of mast cells and sensory nerves in cutaneous vascular hyperpermeability and scratching behavior induced by poly-L-arginine in rats. Eur J Pharmacol 425: 219–227
Wershil BK, Murakami T, Galli SJ 1988 Mast cell-dependent amplification of an immunologically nonspecific inflammatory response. Mast cells are required for the full expression of cutaneous acute inflammation induced by phorbol 12-myristate 13-acetate. J Immunol 140: 2356–2360
Siebenhaar F, Magerl M, Peters EM, Hendrix S, Metz M, Maurer M 2008 Mast cell-driven skin inflammation is impaired in the absence of sensory nerves. J Allergy Clin Immunol 121: 955–961
Onishi N, Kawamoto S, Suzuki H, Santo H, Aki T, Shigeta S, Hashimoto K, Hide M, Ono K 2007 Dietary pulverized konjac glucomannan suppresses scratching behavior and skin inflammatory immune responses in NC/Nga mice. Int Arch Allergy Immunol 144: 95–104
Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D 1997 The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389: 816–824
Vandevska-Radunovic V, Fristad I, Wimalawansa SJ, Kvinnsland IH 2003 CGRP1 and NK1 receptors in postnatal, developing rat dental tissues. Eur J Oral Sci 111: 497–502
Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D 2006 TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124: 1269–1282
Bolcskei K, Helyes Z, Szabo A, Sandor K, Elekes K, Nemeth J, Almasi R, Pinter E, Petho G, Szolcsanyi J 2005 Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice. Pain 117: 368–376
McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM 2007 TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci USA 104: 13525–13530
Scholzen TE, Luger TA 2004 Neutral endopeptidase and angiotensin-converting enzyme—key enzymes terminating the action of neuroendocrine mediators. Exp Dermatol 13: 22–26
Rubinstein I, Iwamoto I, Ueki IF, Borson DB, Nadel JA 1990 Recombinant neutral endopeptidase attenuates substance P-induced plasma extravasation in the guinea pig skin. Int Arch Allergy Appl Immunol 91: 232–238
Kletsas D, Caselgrandi E, Barbieri D, Stathakos D, Franceschi C, Ottaviani E 1998 Neutral endopeptidase-24.11 (NEP) activity in human fibroblasts during development and ageing. Mech Ageing Dev 102: 15–23
Kiernan JA 1977 A study of chemically induced acute inflammation in the skin of the rat. Q J Exp Physiol Cogn Med Sci 62: 151–161
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Ohshima, M., Miyake, M., Takeda, M. et al. Development of Mechanisms Associated With Neurogenic-Mediated Skin Inflammation During the Growthof Rats. Pediatr Res 67, 363–368 (2010). https://doi.org/10.1203/PDR.0b013e3181d026a5
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DOI: https://doi.org/10.1203/PDR.0b013e3181d026a5
