https://orcid.org/0000-0002-6917-9323
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Isabela Souza dos Santos Marchon, Evelynn Dalila do Nascimento Melo, Mirella da Costa Botinhão, Greice Nascimento Pires, João Vitor Rocha Reis, Rodrigo Octavio Mendonça Alves de Souza, Ivana Correa Ramos Leal, André Gustavo Calvano Bonavita, Henrique Rocha Mendonça, Michelle Frazão Muzitano, Leandro Louback da Silva, Paula Lima do Carmo, Juliana Montani Raimundo, Pharmacological potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice, Journal of Pharmacy and Pharmacology, Volume 76, Issue 8, August 2024, Pages 983–994, https://doi.org/10.1093/jpp/rgae057
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Abstract
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.
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.
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.
Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN.
