• RomeroThiago Roberto LimaTRLDepartment of Pharmacology, Institute of Biological Sciences, Pampulha, Belo Horizonte, MG, Brazil. Electronic address: thiromero@ufmg.br., Raquel Rodrigues Soares Santos, Marina Gomes Miranda E Castor, Júlia Alvarenga Petrocchi, Luciana Souza Guzzo, Andre Klein, and DuarteIgor Dimitri GamaIDGDepartment of Pharmacology, Institute of Biological Sciences, Pampulha, Belo Horizonte, MG, Brazil. Electronic address: dimitri@icb.ufmg.br..
• Department of Pharmacology, Institute of Biological Sciences, Pampulha, Belo Horizonte, MG, Brazil. Electronic address: thiromero@ufmg.br.
• Pharmacol Rep. 2018 Aug 1; 70 (4): 784-788.

BackgroundThe aim of this study was to investigate this involvement in not inflammatory model of pain and which opioid receptor subtype mediates noradrenaline-induced peripheral antinociception. Noradrenaline is involved in the intrinsic control of pain-inducing pro-nociceptive effects in the primary afferent nociceptors. However, inflammation can induce various plastic changes in the central and peripheral noradrenergic system that, upon interaction with the immune system, may contribute, in part, to peripheral antinociception.MethodsHyperalgesia was induced by intraplantar injection of prostaglandin E2 (PGE2, 2μg) into the plantar surface of the right hind paw and the paw pressure test to evaluated the hyperalgesia was used. Noradrenaline (NA) was administered locally into right hind paw of Wistar rat (160-200g) alone and after either agents, α2-adrenoceptor antagonist yohimbine, α1-adrenoceptor antagonist prazosin, β-adrenoceptor antagonist propranolol, μ-opioid antagonist clocinnamox, δ-opioid antagonist naltrindole and κ-opioid antagonist nor-binaltorfimina. In addition, the enkephalinase inhibitor bestatin was administered prior to NA low dose.ResultsIntraplantar injection of NA induced peripheral antinociception against hyperalgesia induced by PGE2. This effect was reversed, in dose dependent manner, by intraplantar injection of yohimbine, prazosin, propranolol, clocinnamox and naltrindole. However, injection of nor-binaltorfimina did not alter antinociception of NA after PGE2 hyperalgesia. Bestatin intensified the antinociceptive effects of low-dose of NA.ConclusionBesides the α2-adrenoceptor, the present data provide evidence that, in absence of inflammation, NA activating α1 and β-adrenoceptor induce endogenous opioid release to produce peripheral antinociceptive effect by μ and δ opioid receptors.Copyright © 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

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