ANXIOTROPIC EFFECTS

Background: Acute pain is a complex experience involving both sensory perception and significant affective components, particularly anxiety. This interaction is mediated by shared neural pathways and potentially linked to oxidative stress. This study investigates the comparative anxiotropic effects of orphenadrine and diclofenac, alone and in combination, focusing on their ability to modulate anxiety-like behaviour and associated oxidative damage in acute pain in mice. Methods: Twenty-four mice were allocated into four groups receiving normal saline (10ml/kg), orphenadrine (25mg/kg), diclofenac (50mg/kg), and an orphenadrine–diclofenac combination at the aforementioned doses. Peripheral analgesia was assessed with the acetic-acid–induced writhing assay while anxiety-like behavior was evaluated the following day, using the elevated plus maze. Animals were euthanized, brain tissue was excised and fixed in 10% formalin, and brain MDA was quantified by TBA derivatization and HPLC.
Results: Diclofenac and the orphenadrine-diclofenac combination demonstrated superior analgesic activity (p < 0.01 to p < 0.001). Both orphenadrine (p < 0.0001) and diclofenac (p < 0.001) were associated with significantly elevated MDA levels compared to the control group, while the combination group showed a reduction in MDA compared to either drug alone. All three treatment groups saw a decrease in the time spent in the open arm and a modest increase in time spent in the closed arms of the EPM, compared to the control group (p < 0.001). All drugs were associated with a decrease in the number of entries into the open arm, while orphenadrine uniquely led a significant reduction in closed arm entries (p < 0.01) compared to the control, an effect not seen with diclofenac or the combination groups.
Conclusion: Data from this study shows that all three analgesic treatments were associated with significantly increased anxiety-like behavior and accompanying oxidative damage.