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Analysis of the anti‐allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re‐uptake inhibitor in nerve injury‐induced neuropathic mice
Author(s) -
Gunduz O.,
Topuz R.D.,
Karadag C.H.,
Ulugol A.
Publication year - 2016
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.752
Subject(s) - allodynia , neuropathic pain , pharmacology , cannabinoid , medicine , analgesic , anesthesia , cannabinoid receptor , chemistry , nociception , hyperalgesia , receptor , agonist
Background Combining 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. Methods Partial 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. Results Mechanical 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. Conclusions Overall, our data suggest that combination of a cannabinoid with a selective noradrenaline re‐uptake inhibitor may offer a beneficial treatment option for neuropathic pain.