IN SILICO AND IN VIVO ASSESSMENT OF THE INDIVIDUAL AND COMBINED EFFECTS OF ORPHENADRINE AND DICLOFENAC ON ACUTE NOCICEPTION AND ANXIETY-LIKE BEHAVIOURS IN MICE: POSSIBLE ROLE ON SEROTONERGIC PATHWAY

Pain is a multifaceted phenomenon that encompasses both sensory and emotional elements and is often linked with anxiety. This research investigated the effects of diclofenac, orphenadrine, and their combination on pain perception and anxietyrelated behaviours in mice. Twenty-four albino mice weighing 22–32 g were randomly a signed to four groups and administered saline (10 mL/kg, control), diclofenac (50 mg/kg, intraperitoneally), orphenadrine (25 mg/kg, orally), and orphenadrine (25mg/kg) + diclofenac (50mg/kg). Anxiety-like behaviour was evaluated using the Hole Board Apparatus, while analgesic activity was measured using the Formalin-Induced Paw-Licking Test. In silico studies were also carried out to test for serotonergic activity of the drugs. In the formalin test, diclofenac significantly decreased paw-licking time in both the early and late phases (*p < 0.05), demonstrating strong peripheral analgesic activity. Orphenadrine showed a moderate reduction in nociceptive behaviour, while the combined treatment produced the greatest analgesic effect (***p < 0.001 vs. control, #p < 0.05 vs. orphenadrine), indicating a possible synergistic interaction between the two agents