Comparison of antinociceptive effects of plain lidocaine versus lidocaine complexed with hydroxypropyl-β-cyclodextrin in animal models of acute and persistent orofacial pain
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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.
KeywordsLidocaine Trigeminal neuropathic pain Capsaicin Carrageenan Formalin Hyperalgesia
JGC and RFC conceived and designed research. SBO, EIA, and EG conducted the in vivo experiments. LENF and MFM prepared lidocaine complexed formulation and conducted the in vitro assay. JGC analyzed data and wrote the manuscript. All authors read, revised, and approved the manuscript.
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures were conducted in accordance with the Institutional Committee on the Ethical Use of Animals (authorization no. 1039) and performed in accordance with ethical guidelines, including the policies and recommendations of the International Association for the Study of Pain and according to the recommendations of the Brazilian Agency CONCEA (National Council of Control in Experimental Animals).
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