Analgesic effects of the novel semicarbazide-sensitive amine oxidase inhibitor SZV 1287 in mouse pain models with neuropathic mechanisms: involvement of transient receptor potential vanilloid 1 and ankyrin 1 receptors

Publication date: Available online 10 February 2018 Source:Pharmacological Research Author(s): Ádám Horváth, Valéria Tékus, Noémi Bencze, Nikolett Szentes, Bálint Scheich, Kata Bölcskei, Éva Szőke, Attila Mócsai, Éva Tóth-Sarudy, Péter Mátyus, Erika Pintér, Zsuzsanna Helyes Semicarbazide-sensitive amine oxidase (SSAO) produces tissue irritants by deamination of primary amines, which activate transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors expressed predominantly on nociceptors. Since there are no data about its functions in pain, we studied the effects and mechanisms of action of our novel SSAO inhibitor and dual TRPA1/TRPV1 antagonist multi-target drug SZV 1287 in different pain models. Acute chemonociception was induced by TRPV1 and TRPA1 activation (resiniferatoxin and formalin, respectively), chronic arthritis by K/BxN serum transfer, traumatic mononeuropathy by sciatic nerve ligation. SZV 1287 (20 mg/kg i.p.) was investigated in C57Bl/6J wildtype (WT), TRPA1- (TRPA1−/−) and TRPV1-deficient (TRPV1−/−) mice. Paw mechanonociception was measured by aesthesiometry, thermonociception by hot plate, nocifensive behavior by licking duration, volume by plethysmometry, myeloperoxidase activity by luminescence and plasma extravasation by fluorescence imaging, glia activation in pain-related brain regions by immunohistochemistry. SZV 1287 significantly inhibited both TRPA1 and TRPV1 activation-induced acute chem...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research