Background/Aims: Post-operative nausea and vomiting are common adverse events that require administration of anti-emetic compounds, such as the serotonin 5-HT3 receptor antagonists, but these drugs can also reduce the analgesic efficacy of some analgesics (paracetamol, tramadol). Methods: The present study was designed to explore the effect of 3 serotonin 5-HT3 receptor antagonists on the antinociceptive efficacy of another frequently used post-operative analgesic, nefopam, in the mouse writhing and formalin tests. Results: Pre-treatment with tropisetron, ondansetron or MDL72222 did not significantly modify nefopam antinociception in both tests. However, paracetamol antinociception was blocked by ondansetron in the formalin test. Conclusion: These results provide a rationale for the clinical use of nefopam with anti-emetics during surgery.
1. The aim of the present study was to explore the concept of multimodal anaesthesia using a combination of two non-opioid analgesics, namely nefopam, a centrally acting non-opioid that inhibits monoamine reuptake, and paracetamol, an inhibitor of central cyclo-oxygenases. The antinociceptive characteristics of the combination were evaluated using four different animal models of pain. 2. In the mouse writhing test, antinociceptive properties were observed with ED50 values of 1.5 ± 0.2 and 120.9 ± 14.8 mg/kg for nefopam and paracetamol, respectively. In the mouse formalin test, both compounds significantly inhibited the licking time of the injected hind paw, with ED50 values in the early phase of 4.5 ± 1.1 and 330.7 ± 80.3 mg/kg for nefopam and paracetamol, respectively, compared with 4.3 ± 0.2 and 206.1 ± 45.1 mg/kg for nefopam and paracetamol, respectively, in the inflammatory phase. Isobolographic analysis revealed that this drug combination was synergistic in the writhing test and additive in the formalin test. 3. In a rat incision model of postoperative thermal hyperalgesia, coadministration of nefopam at a non-analgesic dose (3 mg/kg) with paracetamol at a low analgesic dose (300 mg/kg) showed the appearance of a strong antihyperalgesic effect, maintained for at least 3 h. In rat carrageenan-induced tactile allodynia, the combination of low analgesic doses of nefopam (10 or 30 mg/kg) with a non-analgesic dose of paracetamol (30 mg/kg), significantly blocked allodynia with a longer duration of efficacy. 4. In conclusion, coadministration of nefopam with paracetamol is worthy of clinical evaluation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.