Comparison of antinociceptive effects of plain lidocaine versus lidocaine complexed with hydroxypropyl-β-cyclodextrin in animal models of acute and persistent orofacial pain.

Herein, it was investigated whether a complex of lidocaine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) would present a better antinociceptive profile in vivo when compared with plain lidocaine in models of orofacial pain. Plain lidocaine (LDC) and complexed lidocaine (LDC:HP-β-CD) were initially evaluated in vitro to determine the release rate of the two formulations. Subsequently, the effect of both formulations was evaluated in independent groups of rats submitted to the orofacial formalin test, induction of facial heat hyperalgesia by capsaicin and carrageenan, and induction of facial heat and mechanical hyperalgesia by constriction of the infraorbital nerve. LDC:HP-β-CD led to a reduction in the lidocaine release assessed in the in vitro release assay compared to plain LDC. Both formulations presented an antinociceptive effect in all models, but LDC:HP-β-CD showed a better effect in the second phase of the formalin response, in carrageenan-induced heat hyperalgesia, and in the heat hyperalgesia associated to infraorbital nerve constriction. Our results show that complexation improved in vivo antinociceptive effects of LDC, but further studies are necessary to elucidate what properties contribute to the better effect of the complexed formulation on this models and/or what characteristics of the pain model facilitate the action of the complexed formulation.