Participation of Serotonin in Capsaicin-Induced Mouse Ear Edema

Abstract

ABSTRACT-We investigated the involvement of serotonin (5-HT) in mouse ear edema induced by topical application of capsaicin (250 ,ug/ear). Application of capsaicin to the ear caused degranulation of mast cells in skin connective tissue. Capsaicin-induced ear edema was significantly inhibited by preadministration of 5-HT2 receptor antagonists such as ketanserin (2 mg/kg, i.v.) and LY 53857 (1 mg/kg, i.v.), but not 5-HT1-, 5-HT3-and 5-HT4-receptor antagonists. Intradermal injection of a-methyl 5-HT (5-HT2-receptor agonist) and 5-HT into ear skin produced edema formation more potently than 8-OH-DPAT (5-HT1A agonist) and 2-methyl 5-HT (5-HT3 agonist). 5-HT2 antagonists markedly suppressed the edema response to 5-HT and its receptor agonists, whereas any antagonist for 5-HT1, 5-HT3 and 5-HT4-receptors had no effect. Furthermore, 5-HT2-receptor antagonists partly prevented ear edema in response to substance P (SP), a putative mediator of capsaicin-induced edema, and compound 48/80, a releaser of vasoactive amines from mast cells. These results suggest that 5-HT released from mast cells is partly involved in the development of capsaicin-induced mouse ear edema via 5-HT2 receptors in the ear skin.Keywords: Capsaicin, Serotonin (5-HT), Ear edema (mouse), 5-HT receptor, 5-HT-receptor antagonist Capsaicin (8-methyl-N-vanillyl-6-nonenamide), the pungent substance contained in many red peppers, evokes neurogenic inflammatory responses such as axon reflex vasodilation, plasma extravasation and painful sensitization (1). Topical application of capsaicin to the mouse ear produces neurogenic skin inflammation (2, 3), which may be mediated by neuropeptides including substance P (SP) released through activation of primary afferent sensory neurons. Virus and Gebhart (4) have suggested that in addition to SP, serotonin (5-HT) also plays a role in the pharmacological activity of capsaicin. Others have reported that treatment of newborn rats with capsaicin causes an increase in the concentrations of histamine and 5-HT in the rat skin as a result of changes of the mast cell system in response to the permanent degeneration of sensory nerves (5). In fact, evidence exists to indicate that peripheral nerve endings and mast cells are in close spatial and functional association (6 -8). Previous studies have found that methysergide is effective in inhibiting capsaicin-induced mouse ear edema (3). However, clear evidence for the involvement of 5-HT in capsaicin-induced inflammation is lacking.5-HT receptors have been classified into at least four subtypes: 5-HT1, 5-HT2, 5-HT3 and 5-HT4 (9, 10). Among them, 5-HT2 receptors participate in the increase of cutaneous vascular permeability induced by 5-HT in rats (11, 12). 5-HT3 receptors are located on neurons and elicit depolization which results in transmitter release from parasympathetic, sympathetic, sensory and enteric neurons (13). Recent studies have shown that neuropeptides are partly released by mediation of 5-HT3 receptor from capsaicin-sensitive afferent neurons (14). These evidence sugg...

Pereskia aculeata Miller leaves present in vivo topical anti-inflammatory activity in models of acute and chronic dermatitis

“…formation. Glucocorticoids and antihistaminergic drugs may be effective in this test; however COX inhibitors are not capable to respond (Inoue et al, 1993(Inoue et al, , 1995a(Inoue et al, , 1995b. Therefore, the results for capsaicin test were important to identify the neurogenic antiinflammatory potential of HF, and also to corroborate to the other findings presented in this study, more particularly regarding to the lack of HF activity in the AA challenge test.…”

Topical anti-inflammatory effect of Caryocar coriaceum Wittm. (Caryocaraceae) fruit pulp fixed oil on mice ear edema induced by different irritant agents

“…When it contacts with epidermis, capsaicin activates the TRPV1 receptor, which elicits a rapid response via the release of neuropeptides (such as calcitonin gene related peptide, substance P and tachykinins) and monoamimes (histamine and serotonin) (Gábor and Razga, 1992;Inoue et al, 1993Inoue et al, , 1995. Inhibitors of AA metabolites do not reduce the capsaicininduced edema, whereas dexamethasone, antihistamines and bradykinin receptor antagonists present significant antiedematous effect (Mantione and Rodriguez, 1990;Inoue et al, 1995). Moreover, the blockage of Ca 2+ channels and ruthenium red (a capsaicin inhibitor) also show antiedematous effect against capsaicin, but not against AA-induced ear edema (Inoue et al, 1993).…”

Human mast cells are capable of serotonin synthesis and release

“…7 We did find that human mast cells contain and release serotonin, which has been demonstrated to contribute to allergic inflammation in mice. 8 It is of interest that cyproheptadine, which has antiserotonergic properties, is of preferential use in the medical management of individuals with some forms of urticaria. 9 Furthermore, the increased levels of serotonin found in some patients with mastocytosis could be associated with the increased mast cell burden and could help explain a report of a response to cyproheptadine in a pediatric patient with bullous lesions.…”

“…Where studied, the abstract/publication ratios for research presented at meetings of medical specialty or subspecialty organizations range widely, from 11% to 78%. [1][2][3][4][5][6][7][8] In some areas, such as pediatrics and related subspecialties, this outcome is measured at regular intervals and provides a useful benchmark. 2 To our knowledge, abstract/publication ratios have not been previously reported from an allergy/immunology meeting.…”