CENTRAL ADJUVANTS AS MODIFIERS OF THE ANALGETIC ACTIVITY OF PARACETAMOL (EXPERIMENTAL SUBSTANCE)

Abstract

Background. Multimodal analgesia is widely used to enhance pain control and reduce opioid consumption, yet experimental data on paracetamol (acetaminophen) combined with central adjuvant analgesics in visceral pain remain limited.

Purpose – to investigate and substantiate the effectiveness of multimodal combinations of paracetamol with central adjuvants to enhance analgesia in an experimental model of acute visceral pain.

Materials and Methods. The mice (n = 56) were randomly allocated into 8 experimental groups, 7 animals in each. In all experimental groups, a 0.75% acetic acid solution was administered intraperitoneum at a dose of 0.1 mL/10 g body weight as the algogenic agent. The groups differed in the selected multimodal analgesia regimen. Analgesic activity was assessed by the number of abdominal constrictions within 20 minutes after intraperitoneal acetic acid injection. Data were analysed using non-parametric statistics.

Results. Paracetamol monotherapy produced a moderate analgesic effect with a 35.2% reduction in writhing compared with the negative control but remained markedly inferior to morphine. Combinations with gabapentin, pregabalin, and amitriptyline did not significantly enhance analgesia versus paracetamol alone, showing only a modest trend toward further nociception reduction. In contrast, paracetamol with ketamine and paracetamol with dexmedetomidine combinations yielded a significant additional decrease in writhing (44.4% and 50.0% vs control, respectively; p<0.05 vs paracetamol), indicating a synergistic interaction between the central action of paracetamol and NMDA receptor blockade or α₂-adrenergic modulation. None of the combinations achieved the analgesic level of opioid therapy.

Conclusions. In a mouse model of acute visceral pain, paracetamol acts as a centrally active non-opioid analgesic with moderate efficacy. Meaningful potentiation of its analgesic activity is achieved only when combined with central adjuvants that exert complementary mechanisms ketamine and dexmedetomidine supporting their further translational evaluation in multimodal analgesic regimens.