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

AbstractThe 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. Me chanical 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 we re 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 activati on as well microglia and astrocyte activation...
Source: Inflammation - Category: Allergy & Immunology Source Type: research