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01-08-2019 | Analgesics in Dentistry | ORIGINAL ARTICLE

Probucol Ameliorates Complete Freund’s Adjuvant-Induced Hyperalgesia by Targeting Peripheral and Spinal Cord Inflammation

Authors: Amanda Z. Zucoloto, Marília F. Manchope, Sergio M. Borghi, Telma S. dos Santos, Victor Fattori, Stephanie Badaro-Garcia, Doumit Camilios-Neto, Rubia Casagrande, Waldiceu A. Verri Jr

Published in: Inflammation | Issue 4/2019

Abstract

The effect of the lipid-lowering agent probucol in inflammatory hyperalgesia and leukocyte recruitment was evaluated in a model of subacute inflammation by Complete Freund’s adjuvant (CFA). As CFA induces long-lasting nociception characterized by peripheral and spinal cord inflammation, the anti-inflammatory activity of probucol was assessed at both foci. Probucol at 0.3–3 mg/kg was administrated per oral daily starting 24 h after CFA intraplantar injection. Mechanical and thermal hyperalgesia induced by CFA were determined using an electronic anesthesiometer and hot plate apparatus, respectively. Post-treatment with probucol at 3 mg/kg inhibited CFA-induced hyperalgesia over the course of 7 days as well as paw edema. Overt pain-like behaviors, which were determined by the number of flinches and time spent licking paw immediately following CFA injection, were also reduced by probucol at 3 mg/kg administered as a pre-treatment. To investigate the mechanisms underlying the analgesic effect of probucol, neutrophil recruitment to paw was assessed by myeloperoxidase activity, cytokine production, Cox-2 expression, and NF-κB activation in both paw and spinal cord by ELISA. Iba-1, GFAP, and substance P protein expression and nuclear localization of phosphorylated NF-κB were evaluated in the spinal cord by immunofluorescence. Probucol at 3 mg/kg attenuated neutrophil recruitment, cytokine levels, and NF-κB activation as well microglia and astrocyte activation, and substance P staining in the spinal cord. Taken together, the results suggest that probucol exerts its analgesic and anti-inflammatory activity in an experimental model of persistent inflammation by targeting the NF-κB pathway in peripheral and spinal cord foci.

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Title: Probucol Ameliorates Complete Freund’s Adjuvant-Induced Hyperalgesia by Targeting Peripheral and Spinal Cord Inflammation
Authors: Amanda Z. Zucoloto
Marília F. Manchope
Sergio M. Borghi
Telma S. dos Santos
Victor Fattori
Stephanie Badaro-Garcia
Doumit Camilios-Neto
Rubia Casagrande
Waldiceu A. Verri Jr
Publication date: 01-08-2019
Publisher: Springer US
Keyword: Analgesics in Dentistry
Published in: Inflammation / Issue 4/2019
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-019-01011-3

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