• O Gunduz, R D Topuz, C H Karadag, and A Ulugol.
• Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey.
• Eur J Pain. 2016 Mar 1; 20 (3): 465-71.

BackgroundCombining 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 μ-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.© 2015 European Pain Federation - EFIC®

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