Synergism between oral paracetamol and nefopam in a murine model of postoperative pain

Background The use of paracetamol or nefopam for postoperative pain control is limited by the need high doses associated with unwanted effects. Previous works suggest positive interactions between both compounds that may be exploited to obtain potentiation antinociception. Methods Mechanical and heat antinociception induced oral paracetamol, their combination was studied isobolographic analysis in a murine model postsurgical pain. effective produced 50% (ED50) were calculated from log dose–response curves each compound. Subsequently, effects ED8.7s, ED12.5s, ED17.5s ED35s combined assessed. Results Oral dose-dependent relief sensitivity showed higher efficacy reducing mechanical hypersensitivity (ED50 177.3 ± 15.4 mg/kg) than hyperalgesia 278.6 43 mg/kg). similar (ED50s 5.42 0.81 vs. 5.83 0.72). Combinations increasing isoeffective revealed (85.76 mg/kg 1.9 nefopam) (132.67 3.73 synergistic leading 75% 90% antinociception, respectively. These mixtures defined interaction indexes 0.43 0.41 ratios 45:1 35:1 paracetamol:nefopam, same combinations additive inhibition incisional thermal hyperalgesia. Conclusions limitations This work describes antinociceptive low treatment peripheral stimuli. promising results obtained on reflexive nociceptive responses young male mice subjected plantar surgery highlight interest further research evaluating this mixture affective-motivational component females additional age groups. Confirmation pain-relieving safety clinically available European Asian countries could provide useful tool management. Significance Early currently undertreated has been recognized as relevant source chronic efficient treatments facilitate fast-track surgeries patient recovery at home. Here, we identify mouse potent consisting provides multimodal paracetamol–nefopam represent potential pharmacological strategy promotion recovery.