Modulation of COX-2, INF-ɣ, glutamatergic and opioid systems contributes to antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide

• Published in: Chemico-biological interactions Vol. 311; p. 108790
• Main Authors: Reis, Angélica S., Vogt, Ane G., Pinz, Mikaela P., Voss, Guilherme T., da Fonseca, Caren A.R., Paltian, Jaini J., Peglow, Thiago J., Vaucher, Rodrigo A., Echenique, Joanna V.Z., Soares, Mauro P., Schumacher, Ricardo F., Perin, Gelson, Luchese, Cristiane, Wilhelm, Ethel A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 25.09.2019
• Subjects: Allodynia; Analgesic; Anti-edematogenic; Nociception; Pyridine; Selenium; Nociception; Allodynia; Analgesic; Pyridine; Selenium; Anti-edematogenic
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2019.108790

Preclinical assays play a key role in research in research on the neurobiology of pain and the development of novel analgesics. Drugs available for the treatment of inflammatory pain are not fully effective and show adverse effects. Thus, we investigated the antinociceptive, anti-inflammatory and anti-hyperalgesic effects of bis(3-amino-2-pyridine) diselenide (BAPD), a new analgesic drug prototype. BAPD effects were investigated using nociception models induced by chemical (glutamate), immunologic (Freund's Complete Adjuvant - CFA) and thermal stimuli in Swiss mice. Mice were orally (p.o.) treated with BAPD (0.1–50 mg/kg) 30 min prior to the glutamate and hot-plate tests and a time–course (0.5 up to 8 h) of the antinociceptive effect of BAPD (50 mg/kg, p. o.) was evaluated in a CFA model. In the CFA model, BAPD effects on cyclooxygenase-2 (COX-2), tumor necrosis factor (TNFα) and interferon-γ (INF-γ) expression, myeloperoxidase (MPO) activity, oxidative (2,2′-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels) and histological parameters were evaluated. The safety of the compound (50 and 300 mg/kg, p. o.) was verified for 72 h. BAPD reduced the licking time induced by glutamate and caused an increase in latency response to thermal stimulus. Naloxone reversed the antinociceptive effect of BAPD. Paw edema formation induced by glutamate or CFA injection was reduced by BAPD. Mechanical hyperalgesia induced by CFA was attenuated by BAPD. BAPD did not protect against the increase in MPO activity and decrease of the 2,2′-Azino-bis-3-ethylbenzothiazoline 6-sulfonic acid and 2,2-diphe- nyl-1-picrylhydrazyl levels induced by CFA. BAPD protected against histological alterations and reduction on the levels of gene expression COX-2 and INF-γ in the paw of mice exposed to CFA. BAPD was safe at the doses and time evaluated. BAPD exerts acute antinociceptive, anti-inflammatory and anti-hyperalgesic actions, suggesting that it may represent an alternative in the future development of new therapeutic strategies. [Display omitted] •BAPD demonstrated an antinociceptive effect at the dose of 0.1 mg/kg.•BAPD elicited anti-hyperalgesic and anti-inflammatory effects in the CFA model.•BAPD did not alter locomotor activity or induce toxicity.•Effects of BAPD seem to be due to a modulation of opioid and glutamatergic systems.•Levels of expression COX-2 and INF-γ were reduced by BAPD.