Osaze Edosuyi

EFFECT OF ORPHENADRINE–DICLOFENAC COMBINATION ON COX-2 EXPRESSION AND EXPLORATORY BEHAVIOUR IN ACETIC ACID–INDUCED NOCICEPTION IN MURINE MODELS

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Publication Type
Abstract
Background: Pain and inflammation remain major health concerns that reduce quality of life despite many available treatments. Diclofenac, a nonsteroidal anti-inflammatory drug, and orphenadrine, a centrally acting muscle relaxant, target different pain pathways. This study investigates whether their combined use enhances analgesic and anti-inflammatory effects, offering a safer and more effective approach to pain management. Method: Twenty-four Swiss albino mice were divided into four groups to receive saline, diclofenac (50 mg/kg), orphenadrine (25 mg/kg) and ophenadrine-diclofenac (25 mg/kg-50 mg/kg). Analgesic effects were assessed using the acetic acid–induced writhing and hole- board tests, while COX inhibition was evaluated using the quantitative polymerase chain reaction assay. Data were expressed as Mean ± SEM and analyzed using one-way ANOVA, with significance set at p < 0.05. Result: Diclofenac (1.67 ± 0.76), orphenadrine (2.17 ± 0.95), and their combination (0.00 ± 0.00) significantly reduced writhes compared to control (6.00 ± 1.53; p < 0.05). COX-2 levels were markedly lower in diclofenac (88.32 ± 1.18), orphenadrine (27.59 ± 2.26), and combination (68.30 ± 1.43) treated groups versus control (95.26 ± 1.88). In the hole-board test, the combination group (24.33 ± 1.59) maintained head dips comparable to the control group. Conclusion: Diclofenac and orphenadrine provide complementary pain relief, with diclofenac acting peripherally and orphenadrine centrally. Their combination synergistically abolished writhing, balanced COX-2 activity, and preserved normal exploratory behaviour. These results highlight the diclofenac–orphenadrine combination as an effective multimodal analgesic that enhances pain control while supporting central function.
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BEHAVIOURAL AND ANXIOTROPIC EFFECTS OF ORPHENADRINE AND DICLOFENAC IN ACUTE PAIN IN SWISS ALBINO MICE

Year of Publication
Publication Type
Abstract
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.
Supervisor(s)
co-supervisor