A Freshwater Pearl Mussel Polysaccharide Alleviates Inflammatory Pain by Targeting Peripheral Cytokines and Spinal...

Mussel polysaccharide (MP), a bioactive component derived from Hyriopsis cumingii and Cristaria plicata, exhibits promising anti-inflammatory and analgesic effects in preclinical studies. For its unclear therapeutic mechanisms, we systematically evaluated MP's efficacy and action mechanisms in a Complete Freund's Adjuvant (CFA)-induced rat pain model. Sixty male SD rats were divided into control, CFA, CFA + celecoxib, and CFA + MP (1.62, 0.81, 0.27 g kg^-1) groups. Treatments began 3 days post-CFA. Paw withdrawal threshold (PWT), thermal tail-flick latency (TFL), paw volume (PV), and paw inflammatory scores (PIS) were measured periodically. At Day 14 after drug administration, serum IL-6/TNF-α were quantified using ELISA, and paw histopathological and complete blood count (CBC) were analyzed. Spinal NLRP3/GFAP expression was detected via immunohistochemistry. MP dose-dependently improved PWT/TFL, with 0.81 and 1.62 g kg^-1 dosage groups showing the most pronounced effects. It suppressed ipsilateral/contralateral PV, lowered serum IL-6/TNF-α levels, and decreased the WBC count and LYMPH%. H&E staining showed attenuated neutrophil infiltration and necrosis. Additionally, MP downregulated spinal GFAP expression and attenuated NLRP3 immunoreactivity, suggesting a potential modulation of astrocyte activation and neuroinflammatory levels. MP alleviates inflammatory pain by suppressing peripheral inflammation and modulating spinal neuroinflammation, associated with attenuated astrocyte activation and NLRP3 expression. These findings highlight MP as a promising therapeutic candidate for inflammatory pain management.