Involvement of unique mechanisms in the induction of scratching behavior in BALB/c mice by compound 48/80.

The root of Paeonia lactiflora PALL (PL, Family Paeoniaceae) has been used frequently as an antipyretic and anti-inflammatory agent in traditional medicines of Korea, China and Japan To evaluate antiallergic effect of PL, we isolated its main constituents, paeoniflorin and paeonol, and evaluated in vivo their inhibitory effects against passive cutaenous anaphylaxis (PCA) reaction induced by IgE-antigen complex and scratching behaviors induced by compound 48/80 PL, paeoniflorin and paeonol potently inhibited PCA reaction and scratching behaviors in mice Paeoniflorin exhibited the most potent inhibition against scratching behaviors and the acetic acid-induced writhing syndrome in mice Paeonol most potently inhibited PCA reaction and mast cells degranulation These findings suggest that PL can improve IgE-induced anaphylaxis and scratching behaviors, and may be due to the effect of its constituents, paeoniflorin and paeonol

Antiallergic effect of the root of Paeonia lactiflora and its constituents paeoniflorin and paeonol.

Generalized pruritus is a distressing symptom that can occur in several dermatologic and systemic disorders. Generalized pruritus of unknown origin is that which affects patients without any underlying dermatologic or systemic disorder and is unassociated with rash. It most commonly occurs in older patients and persists for long periods, from months to years. In many cases, the itching may be due to reduced water content of the skin, without overt dryness. Failure of the normal processing of the itching sensation along the course of central and peripheral sensory pathways may also play a role.

https://jamanetwork.com/journals/jamadermatology/articlepdf/401003/dce40019_1507_1509.pdf

Efficacy of gabapentin in the management of pruritus of unknown origin.

Intradermal microinjection of the pruritogen histamine, or the algogen capsaicin, in the mouse cheek differentially elicits mainly hindlimb scratching or ipsilateral forelimb wiping, respectively. We investigated the dose-dependency of these responses elicited by various pruritogens and algogens, and µ-opioid modulation. Histamine, 5-hydro-xytryptamine (5-HT) and agonists of protease-activated receptors PAR-2 and PAR-4, all elicited dose-related hindlimb scratching bouts with little forelimb wiping. In contrast, capsaicin, allyl isothiocyanate and bradykinin elicited dose-related forelimb wiping with little scratching. Morphine reduced capsaicin-evoked wiping but not pruritogen-evoked scratching. The µ-antagonist naltrexone decreased pruritogen-evoked scratching but not capsaicin-evoked wiping. A cowhage spicule inserted intradermal elicited equivalent scratching and wiping, while inactivated cowhage spicules loaded with histamine or capsaicin elicited significantly more scratching or wiping, respectively. The mouse cheek injection model appears to be a useful behavioral test that distinguishes between itch and pain.

Differential itch- and pain-related behavioral responses and µ-opoid modulation in mice.

Endogenous opiates: 2000.

Background: Itching in humans is attenuated by µ-opioid receptor antagonists. ICR mice display increases in scratching behavior upon induction of IgE-mediated passive cutaneous anaphylaxis (PCA), or intradermal injection of compound 48/80 or histamine. Methods: Cutaneous reactions were induced in ICR mice by IgE-mediated PCA, compound 48/80 and histamine, and the scratching behavior associated with the cutaneous reactions was evaluated. Results: Naloxone and nalmefene reduced the incidence of scratching behavior associated with PCA. Naloxone also inhibited the induction of scratching behavior caused by compound 48/80 and histamine. Naloxone did not affect the increase in vascular permeability caused by PCA and injection of compound 48/80. Conclusion: Scratching behavior in mice may be induced by a sensation or a mechanism similar to itching in humans and should become a useful model for examining itching in humans.

Inhibition of Passive Cutaneous Anaphylaxis-associated Scratching Behavior by μ-Opioid Receptor Antagonists in ICR Mice.

The effect of overproduction of interleukin (IL) 5 on the allergic cutaneous response was investigated in transgenic mice overexpressing IL-5. Five repeated topical applications of 2, 4-dinitrofluorobenzene (DNFB) to the ears of mice resulted in allergic dermatitis on the ears as well as significant elevation in dinitrophenol-specific IgE antibody and total IgE in the serum in both wild-type and transgenic mice. The development of dermatitis as measured by skin thickness and histopathological changes were potentiated in the transgenic mice. In IL-5 transgenic mice, significant accumulation of eosinophils in skin lesions was observed after five paintings of DNFB, and the magnitudes of eosinophilia and IL-5 messenger RNA expression were significantly higher than in wild-type mice. The dinitrophenol-specific and total IgE in the serum were higher in IL-5 transgenic mice. The late phase reaction of IgE antibody-mediated biphasic cutaneous response was potentiated in IL-5 transgenic mice. The magnitudes of vasopermeability increase by passive cutaneous anaphylaxis, serotonin, and platelet-activating factor were similar in both mice. These results indicate that overproduction of IL-5 resulted in the potentiation of DNFB-induced dermatitis by elevation of IgE production, IgE-mediated allergic late-phase cutaneous reaction, and eosinophilia in the skin lesion.

Effect of Overproduction of Interleukin 5 on Dinitrofluorobenzene-induced Allergic Cutaneous Response in Mice.

The effect of a newly synthesized compound, HSR-609, on rat experimental rhinitis was investigated. In the first part of the study, a new experimental nasal allergic late phase eosinophilia model in Brown Norway (BN) rats was investigated. The increase in the number of antigen inhalations resulted in the proportional increase in the number of inflammatory cells such as macrophages, eosinophils and neutrophils in the nasal cavity lavage fluid (NCLF) at 5 h after each inhalation. The number of inflammatory cells reached a maximum 8 h after the antigen perfusion. Submaximum response was observed at 5 h after the antigen provocation. In this system, the serum IgG and IgE antibody titers measured by homologous passive cutaneous anaphylaxis were 160 and 640, respectively. In the second part of the study, the effects of prednisolone, cetirizine and a newly synthesized amphoteric antiallergic agent, HSR-609, on this allergic late nasal eosinophilia and neutrophilia in BN rats were investigated. Prednisolone and HSR-609 significantly inhibited the increase in the number of eosinophils in the NCLF but not cetirizine. Furthermore, prednisolone showed the inhibition of the increase in the number of macrophages and neutrophils in NCLF. These results suggest that this late phase eosinophilia model in the nose of BN rats may be useful for investigating the therapeutic drugs for nasal allergy and a newly synthesized amphoteric antiallergic agent, HSR-609, may be useful for the treatment of allergic rhinitis with eosinophilia.

Effects of an Amphoteric Antiallergic Agent, HSR-609,on Antigen-induced Late Phase Nasal Eosinophilia in Brown Norway Rats.

A newly synthesized anti-allergic agent, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10), has the capacity to inhibit the effector phase of delayed hypersensitivity reactions. In the present paper, the effect of IG-10 was studied on the generation of superoxide anion (O2) from macrophages, on macrophage chemotaxis, and on the activity of lymphokines such as skin reactive factor (SRF), macrophage migration inhibitory factor (MIF) and monocyte/macrophage chemotactic factor (MCF) in guinea pigs. Oral administration of IG-10 (50-200 mg/kg) inhibited SRF-induced skin erythema in a dose-dependent manner. In vitro, this agent (10(-7) -10(-5) g/ml) did not inhibit the generation of O2- from macrophages. The agent (10(-7) -10(-6) g/ml) significantly inhibited the activity of MIF and this inhibition was not due to the facilitation of normal migration. For macrophage chemotaxis, IG-10 (10(-8) -10(-6) g/ml) significantly inhibited MCF-induced chemotaxis. The agent also depressed the macrophage chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine but not the chemotaxis induced by E. coli culture filtrate. The inhibitory action of IG-10 on MCF activity was not influenced by antiglucocorticoid agents such as 17 alpha-methyltestosterone and androstenedione which reverse significantly the inhibitory action of glucocorticoids. The inhibitory action of IG-10 was relatively dependent on exogenous Ca2+ and Mg2+, and was antagonized by dbc-GMP.

Inhibition of Delayed Hypersensitivity Reactions by a New Agent, Cis-1-Methyl-4-Isohexycyclohexane Carboxylic Acid (IG-10). II. : The Mechanism Regarding the Action on Lymphokines.

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