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

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of paclitaxel treatment.
• Current management strategies for CIPN are limited, necessitating novel therapeutic approaches.

Purpose of the Study:

• To investigate the efficacy of celecoxib in mitigating paclitaxel-induced peripheral neuropathy in a rat model.
• To elucidate the underlying mechanisms involving the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway.

Main Methods:

• Paclitaxel-induced neuropathy was established in rats.
• Celecoxib treatment efficacy was assessed using behavioral assays (thermal/mechanical hypersensitivity) and histological analyses (DRG, sciatic nerve, plantar skin).
• In vitro studies examined celecoxib's effects on dorsal root ganglion (DRG) neuronal apoptosis and survival via COX-2/PGE2 signaling.

Main Results:

• Celecoxib significantly attenuated thermal and mechanical hypersensitivity in paclitaxel-treated rats.
• Histological examination revealed that celecoxib ameliorated neuronal damage in the DRG, sciatic nerve, and plantar skin.
• Celecoxib downregulated the expression of COX-2, PGE2, and MHC, and suppressed DRG neuronal apoptosis in vitro, promoting neuronal survival.

Conclusions:

• Celecoxib demonstrates significant neuroprotective effects against paclitaxel-induced peripheral neuropathy.
• The COX-2/PGE2 pathway is a viable therapeutic target for managing CIPN.
• Celecoxib exhibits potential for long-term clinical use in CIPN management and warrants further investigation for combination therapies.