Celecoxib Mitigates Paclitaxel-Induced Peripheral Neuropathy Through Modulation of the COX-2/PGE2 Pathway in Rats

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe paclitaxel-associated adverse effect in cancer treatment. This study explored celecoxib's therapeutic efficacy against paclitaxel-induced neuropathy in rats via the COX-2/PGE2 pathway. Behavioral assays revealed celecoxib attenuated paclitaxel-induced thermal/mechanical hypersensitivity; histological analyses demonstrated it ameliorated neuronal damage in the DRG, sciatic nerve, and plantar skin. Celecoxib also downregulated paclitaxel-induced upregulation of COX-2, PGE2, and MHC in these tissues. In vitro, it suppressed DRG neuronal apoptosis and promoted survival by regulating COX-2/PGE2 signaling. Its effects were comparable to COX-2 gene silencing, with a favorable preclinical safety profile supporting long-term clinical use. These findings elucidate the neuroprotective mechanism of celecoxib, propose COX-2/PGE2 as a therapeutic target for CIPN, and lay a foundation for relevant combination therapy research, highlighting celecoxib's potential in CIPN management.