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

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

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

Inflammation. 2019 Aug;42(4):1474-1490.

PMID: 31011926

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1173019298	Probucol-(propyl-13C3)		1173019-29-8	Price

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