Resveratrol therapy modulates inflammatory biomarkers and reverses mechanical allodynia in rats subjected to a temporomandibular joint arthritis model

Toothaches, headaches, and chronic illnesses, including trigeminal neuralgia and temporomandibular joint dysfunction, are common craniofacial pain conditions. Resveratrol, a polyphenolic compound characterized by its antioxidant and anti-inflammatory properties, has shown therapeutic potential across multiple neurological disorders. This study aimed to evaluate the antinociceptive, anti-inflammatory, behavioral, and neurochemical impacts of Resveratrol in rats experiencing chronic inflammatory orofacial pain. A unilateral intra-trigeminal neuralgia injection (50 µL) of Complete Freund’s Adjuvant in adult male Wistar rats was used to induce pain. Resveratrol at 20, 40, or 80 mg/kg was administered to SHAM (saline) and Pain rats for 14 days. Mechanical allodynia (von Frey test) and thermal nociceptive sensitivity (acetone test) were assessed. Cytokine levels (TNF-α, IL-10, and IL-4) were quantified in the spinal cord and brainstem. Animals treated with Resveratrol demonstrated a progressive recovery in mechanical thresholds over time, with RES40 and RES80 groups exhibiting significantly higher thresholds (day 17) compared to the Pain group. Increased grooming time was observed during the acetone test in rats submitted to the pain model (day 3), with no significant effects of treatment (day 17). The pain model significantly increased spinal cord levels of TNF-α and IL-4. All doses of Resveratrol effectively mitigated the elevation in TNF-α levels in the spinal cord, while only RES80 potentiated the increase in IL-4 levels induced by the pain model. Despite limitations related to the pharmacokinetic characteristics of RES, the results indicate that this compound holds translational potential as an adjuvant in the management of painful inflammatory conditions, including TMJ disorders.