Gunduz, O.Topuz, R. D.Karadag, C. H.Ulugol, A.2024-06-122024-06-1220161090-38011532-2149https://doi.org/10.1002/ejp.752https://hdl.handle.net/20.500.14551/25338BackgroundCombining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing -opioid receptor agonism and noradrenaline re-uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2 and the selective noradrenaline re-uptake inhibitor maprotiline exert anti-allodynic synergy on nerve-injured neuropathic mice. MethodsPartial tight ligation of the sciatic nerve was made in mice; on pre-operative and post-operative 15 days basal mechanical allodynia, cold allodynia and motor function were assessed using von Frey filaments, hot/cold plate and rota rod apparatus. ResultsMechanical and cold allodynia developed in all groups on post-operative 15 days. Development of cold allodynia was statistically significant in all groups (p<0.05); therefore, cold allodynia was used in combination studies. As shown by isobolographic analysis, interactions of 1:1 and 3:1 ratios of WIN 55,212-2:maprotiline combinations were supra-additive, whereas 1:3 ratio was sub-additive. ConclusionsOverall, our data suggest that combination of a cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a beneficial treatment option for neuropathic pain.en10.1002/ejp.752info:eu-repo/semantics/closedAccessRat Formalin TestChronic PainTactile AllodyniaReceptor AgonistWin 55,212-2TapentadolToleranceAntinociceptionWin-55,212-2AnalgesicsArticle203465471Q2WOS:0003704465000142-s2.0-8495883970426206340Q1