Systemic curcumin administration mitigates neuropathic pain in a rat model of trigeminal neuralgia by suppressing TNF-α and pSTAT3 signaling

Trigeminal neuralgia (TN) is a debilitating neuropathic facial pain disorder characterized by sudden, severe paroxysmal pain that markedly impairs quality of life. Although current pharmacological treatments provide pain relief, their adverse effects highlight the need for safer alternative therapies. Curcumin, a natural polyphenol, exhibits anti-inflammatory and neuroprotective properties with minimal side effects. In this study, we examined the impact of intraperitoneal curcumin administration on the trigeminal ganglia in a TN rat model induced by unilateral infraorbital nerve constriction (IONC). Behavioral tests revealed that curcumin significantly reduced mechanical hypersensitivity compared with vehicle-treated controls. Immunohistochemical analysis showed decreased expression of glial fibrillary acidic protein (GFAP) and activating transcription factor 3 (ATF3), established markers of satellite glial cell (SGC) activation and neuronal stress in the trigeminal ganglia. Furthermore, curcumin administration reduced tumor necrosis factor-α (TNF-α) expression and modulated phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activity. These findings suggest that curcumin alleviates neuropathic pain by suppressing glial activation and pSTAT3-related pro-inflammatory signaling. Curcumin may therefore represent a promising potential therapeutic candidate for TN, warranting further investigation into its clinical applicability and underlying mechanisms.