title: Differential effects of topically applied formalin and aromatic compounds on neurogenic-mediated microvascular leakage in rat skin.
abstract: Various volatile organic compounds (VOCs) act as a causative agent of skin inflammation. We investigated the effect of topical application of several VOCs and formalin on microvascular leakage in rat skin. We tested capsaicin, which is a reagent that specifically causes the skin response via endogenously released tachykinins. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. After shaving the abdomen, we applied formalin, m-xylene, toluene, styrene, benzene, ethylbenzene, acetone, diethyl ether, hexane, heptane, cyclohexane and capsaicin to the skin. At 40min after application, skin samples were collected. Among all of the VOCs tested, all of the aromatic compounds significantly produced skin microvascular leakage that was similar to formalin and capsaicin. We also investigated the skin responses seen after the intravenous administration of CP-99,994 (1.5 or 5mg/kg), which is a tachykinin NK1 receptor antagonist, ketotifen (1 or 3mg/kg), which is a histamine H1 receptor antagonist that stabilizes the mast cells, and the topical application of capsazepine (22.5 or 50mM), which is the transient receptor potential vanilloid 1 (TRPV1) antagonist. The response induced by formalin and capsaicin was completely inhibited by CP-99,994. On the other hand, the antagonist partially reduced the response induced by m-xylene, toluene and styrene by 39%, 50% and 46%, respectively. Capsazepine and ketotifen did not alter the response induced by formalin or any of the aromatic compounds. Like capsaicin, formalin and the aromatic compounds at least partially caused skin microvascular leakage, which was due to tachykinin NK1 receptor activation related to the release of tachykinins from the sensory nerve endings. However, it is unlikely that mast cells and TRPV1 play an important role in the skin response.
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Futamura
authors.forename: Shiho
authors.initials: S
authors.lastname: Goto
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kimura
authors.forename: Izumi
authors.initials: I
authors.lastname: Kimoto
authors.forename: Mio
authors.initials: M
authors.lastname: Miyake
authors.forename: Komei
authors.initials: K
authors.lastname: Ito
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Sakamoto
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000982:Antipruritics / Q000494:pharmacology; D019559:Capillary Leak Syndrome / Q000139:chemically induced* / Q000473:pathology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D004202:Disinfectants / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000008:administration & dosage / Q000633:toxicity*; D006841:Hydrocarbons, Aromatic / Q000008:administration & dosage / Q000633:toxicity*; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D020078:Neurogenic Inflammation / Q000139:chemically induced* / Q000473:pathology; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000473:pathology*
chemical_list: D000982:Antipruritics; D004202:Disinfectants; D006841:Hydrocarbons, Aromatic; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D005557:Formaldehyde; C071423:capsazepine; D002211:Capsaicin; D007665:Ketotifen