SYNERGY OF COX-2 INHIBITION AND CENTRAL MODULATION IN EXPERIMENTAL MODELS: ADJUVANT STRATEGIES FOR PARECOXIB SODIUM
DOI:
https://doi.org/10.32689/2663-0672-2025-3-9Keywords:
parecoxib sodium, multimodal analgesia, adjuvant analgesics, dexmedetomidine, ketamineAbstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are regarded as core components of multimodal analgesia. Parecoxib sodium, a parenteral selective COX-2 inhibitor, provides a rapid onset of action; however, its effect may be insufficient under pronounced nociceptive input. Centrally acting adjuvant analgesics (α₂-adrenergic agonists, NMDA-receptor antagonists, modulators of the α₂δ subunit of voltage-gated calcium channels, and tricyclic antidepressants) can potentiate the peripheral actions of NSAIDs. Purpose – to assess the impact of adjuvant analgesics from different pharmacological classes on the magnitude of the analgesic effect of parecoxib sodium in a model of acute visceral pain. Materials and Methods. Male mice (n=56) were randomized into eight groups of seven animals each. Acute visceral pain was modeled using the acetic acid induced writhing test. The number of abdominal constrictions (“writhes”) recorded over 20 minutes after intraperitoneal injection of 0.75% acetic acid served as the nociception index. Results. Parecoxib sodium as monotherapy reduced the number of writhes by 33.2% versus control. Combining parecoxib with adjuvant analgesics further enhanced the analgesic effect; differences for combinations with gabapentin, pregabalin, and amitriptyline did not reach statistical significance. The largest effects were observed for combinations with ketamine – 48.9% (27.3±2.5; p=0.04 vs monotherapy) and dexmedetomidine – 51.3% (26.0±1.7; p=0.01 vs monotherapy). Conclusions. Experimental data confirm that adding adjuvant analgesics from different pharmacological classes to parecoxib sodium augments its analgesic action in an acute visceral pain model. The most effective combinations were parecoxib sodium with dexmedetomidine or ketamine, whose effects approached that of morphine and indicate pronounced synergy between peripheral COX-2 blockade and central NMDA- or α₂-adrenergic – mediated modulation.
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