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- Title
Pharmacological potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice.
- Authors
Marchon, Isabela Souza dos Santos; Melo, Evelynn Dalila do Nascimento; Botinhão, Mirella da Costa; Pires, Greice Nascimento; Reis, João Vitor Rocha; de Souza, Rodrigo Octavio Mendonça Alves; Leal, Ivana Correa Ramos; Bonavita, André Gustavo Calvano; Mendonça, Henrique Rocha; Muzitano, Michelle Frazão; da Silva, Leandro Louback; do Carmo, Paula Lima; Raimundo, Juliana Montani
- 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.
- Subjects
MUSCARINIC receptors; OPIOID receptors; NEURALGIA; SCIATIC nerve; MYELOPEROXIDASE; CHALCONE
- Publication
Journal of Pharmacy & Pharmacology, 2024, Vol 76, Issue 8, p983
- ISSN
0022-3573
- Publication type
Academic Journal
- DOI
10.1093/jpp/rgae057