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Öğe The false-positive responses of analgesic drugs to the intradermal serotonin- and compound 48/80-induced scratches as an animal model of itch(Nencki Inst Experimental Biology, 2016) Ilkaya, Fatih; Yesilyurt, Ozgur; Seyrek, Melik; Gunduz, Ozgur; Ide, Tayfun; Akar, Ahmet; Ulugol, AhmetIntradermal injection of pruritogens such as serotonin, histamine and compound 48/80 into the skin and then, the evaluation of the scratching behavior is the commonly used animal model to advance pruritic research and drug development. However, predictive validity of this model is poorly documented. There is a close interaction between itch and pain sensations with regard to mediation through an anatomically and functionally identical neuronal pathway. One approach is whether the existing animal model of itch differentiates itch or pain to show efficacy of clinically effective analgesic drugs as a back translation. In this study, we explored the effects of different group of analgesic drugs on serotonin and compound 48/80-induced scratching behavior in Balb-C mice. Serotonin (25 mu g) and compound 48/80 (100 mu g) was injected intradermally in a volume of 50 mu l into the rostra! part of skin on the back of male mice and scratches were counted for a 30-min observation period. Morphine (1, 3, 10 mg/kg), tramadol (20, 40, 80 mg/kg), cannabinoid agonist CP 55,940 (0.1, 0.3, 1 mg/kg), paracetamol (100, 200, 300 mg/kg) and diclofenac (50, 100, 200 mg/kg) were given intraperitoneally 30 min prior to pruritogen injection. The analgesic drugs dose dependently blocked serotonin and compound 48/80-induced straching behavior with exerting complete inhibition at certain doses. Our data suggests that intradermal pruritogen-induced scratching models may not discriminate pain and itch sensations and give false positive results when standard analgesic drugs are used.Öğe Involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception(Pergamon-Elsevier Science Ltd, 2012) Dogrul, Ahmet; Seyrek, Melik; Yalcin, Bulent; Ulugol, AhmetCannabinoids produce antinociceptive and antihyperalgesic effects mainly through activation of the inhibitory CB1 receptors. The demonstration that antinociceptive effects of systemic cannabinoids are significantly diminished following surgical dorsolateral funiculus lesion provides evidence that supraspinal sites and descending pain modulatory pathways play crucial roles in systemic cannabinoid analgesia. In this review, we will firstly provide a background, brief overview of descending modulatory pathways followed by descending pathways implicated in cannabinoid analgesia. We will then describe the recent evidence of the involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception. This review will provide evidences that systemically administered cannabinoids reinforce the descending serotonergic and noradrenergic pathways to produce acute antinociceptive effects via spinal 5-HT7, 5-HT2A and alpha-2 adrenoceptors activation. (C) 2012 Elsevier Inc. All rights reserved.Öğe THE PROBLEMATIC SENSITIVITY OF INTRADERMAL SEROTONIN AND HISTAMINE INDUCED STRACHING MODEL TO ANALGESIC DRUGS AS AN ANIMAL MODEL OF ITCH(Acta Dermato-Venereologica, 2013) Ilkaya, Fatih; Yesilyurt, Ozgur; Seyrek, Melik; Gunduz, Ozgur; Ide, Tayfun; Akar, Ahmet; Ulugol, Ahmet[Abstract Not Available]