Artigo Produção Nacional Revisado por pares

Pharmacological potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice

2024; Oxford University Press; Volume: 76; Issue: 8 Linguagem: Inglês

10.1093/jpp/rgae057

ISSN

2042-7158

Autores

Isabela Souza dos Santos Marchon, Evelynn Dalila do Nascimento Melo, Mirella da Costa Botinhão, Greice Nascimento Pires, João Vitor Rocha Reis, Rodrigo O. M. A. de Souza, Ivana Corrêa Ramos Leal, André Gustavo Calvano Bonavita, Henrique Rocha Mendonça, Michelle Frazão Muzitano, Leandro Louback da Silva, Paula Lima do Carmo, Juliana Montani Raimundo,

Tópico(s)

Pharmacological Effects of Natural Compounds

Resumo

Abstract Objectives This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice. Methods The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve. Key findings DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice. Conclusions Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN.

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