Antinociceptive and Anti-Inflammatory Mechanisms of Methanol Extract of Securidaca longepedunculata Root in Rodent Models

Securidaca longepedunculata is a multipurpose medicinal plant distributed across the Guinea savannah zones of North West and North Central Nigeria, extensively used by traditional healers for pain, inflammatory conditions, headache, and rheumatic diseases. Despite widespread traditional use, the mechanistic basis of its antinociceptive and anti-inflammatory effects has not been fully elucidated. This study investigates the antinociceptive and anti-inflammatory mechanisms of the methanol root extract of Securidaca longepedunculata using a battery of rodent pain and inflammation models. Antinociception was evaluated using acetic acid-induced writhing, formalin test (Phase I and II), hot plate, and tail-flick tests to distinguish centrally and peripherally mediated analgesic components. Mechanism-specific antagonism experiments used naloxone (opioid antagonist), glibenclamide (K-ATP channel blocker), and atropine (muscarinic antagonist) to identify signal transduction pathways. Anti-inflammatory activity was assessed using carrageenan paw oedema, cotton pellet granuloma, and LPS-induced TNF-alpha and IL-6 production assays. Significant dose-dependent antinociception was observed across all pain models. Naloxone partially reversed the analgesic effect, implicating opioidergic involvement. Glibenclamide did not significantly alter analgesia. Phase II formalin test inhibition confirmed peripheral anti-inflammatory activity. TNF-alpha and IL-6 production were significantly suppressed. Methyl salicylate and terpenoid fractions from HPLC were identified as probable contributors. These results delineate opioidergic and peripheral anti-inflammatory dual mechanisms of action for Securidaca longepedunculata. Keywords: Securidaca longepedunculata, antinociceptive, anti-inflammatory, opioidergic, mechanism of action