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. 2018 May 28;11:180. doi: 10.3389/fnmol.2018.00180

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Copyright © 2018 Reynoso-Moreno, Chicca, Flores-Soto, Viveros-Paredes and Gertsch.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Polypharmacological effects observed after 3 days treatment with 10 mg/kg of WOBE437. (A) The antiallodynia effects of 10 mg/kg of WOBE437 after single dose were significantly reversed by the CB2 receptor antagonist SR144528 and the TRPV1 antagonist capsazepine. In the 3 days treatment scheme, (B) antiallodynia and (C) the antiinflammatory effects were prevented by antagonists of the CB1 receptor (rimonabant), CB2 receptor (SR144528) and PPARγ (GW9662). Rimonabant, SR144528 or GW9662 were administered i.p. 30 min before WOBE437. Allodynia was evaluated by mechanical sensitivity and edema measuring knee diameter; both were assessed 1 h after WOBE437 treatment. All compounds were administered i.p. Groups were compared using Kruskal–Wallis test followed by Mann–Whitney test. ^∗p < 0.05 vs. ipsilateral/vehicle; ^#p < 0.05 vs. contralateral/vehicle; ^&p < 0.05 vs. WOBE437; i.p., intraperitoneally.