Dose and parameter specific effects of curcumin on neuropathic pain, cavity formation, and non-coding RNA expression...

Neuropathic pain (NP) represents one of the most frequent complications following spinal cord injury (SCI) and is associated with dysregulation of non-coding RNAs (ncRNAs). Curcumin possesses anti-inflammatory and neuroprotective properties. This study investigated the dose-dependent effects of curcumin-a compound with anti-inflammatory and neuroprotective properties-on pain-related behaviors and ncRNA expression after SCI. Male Wistar rats (n = 8 per group) were randomly assigned to 5 groups: Control (no surgery, no treatment), Sham (only laminectomy), SCI (clip-compression injury at the T11-T12 vertebral level), Cur100 and Cur200 (Curcumin at 100 and 200 mg/kg given orally 30 min after SCI for 10 consecutive days). Behavioral tests (acetone drop for cold allodynia, tail-flick for thermal hyperalgesia) were conducted over six weeks. Histological (H&E staining for cavity size) and molecular (qPCR for lncRNAs H19, GAS5, CRNDE and miRNAs miR-21-5p, miR-29a-3p) analyses were performed. Data were analyzed with PRISM software. At the endpoint, SCI induced significant cold allodynia, thermal hyperalgesia along with significant upregulation of all target ncRNAs. Curcumin treatment at both doses attenuated NP and modulated ncRNA expression in a parameter-dependent manner-where effects varied based on the specific outcome measured. The higher dose (200 mg/kg) provided greater neuroprotection and more effectively reduced thermal hyperalgesia, while the lower dose (100 mg/kg) was more potent in alleviating cold allodynia and selectively downregulating pro-inflammatory ncRNAs (H19, GAS5, miR-21-5p). These findings highlight the parameter-specificity of curcumin's therapeutic effects, suggesting that optimal dosing should be tailored according to the targeted pain modality and molecular pathway.