期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 273, 期 -, 页码 180-189出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2017.06.014
关键词
Neuropathy; Hyperalgesia; Oxidative stress; Flavonoids
资金
- Sao Paulo Research Foundation [2011/19670-0, 2013/08216-2]
- Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil)
- Financiadora de Estudos e Projetos and Secretaria de Estado da Ciencia, Tecnologia e Ensino Superior do Parana (FINEP/SETI-PR, Brazil) [01.12.0294.00 (0476/11)]
- CAPES/Fundacao Araucaria post-doctoral fellowship
Injury or dysfunction of somatosensory system induces a complex syndrome called neuropathic pain, which still needs adequate pharmacological control. The current pharmacological treatments were in part developed from natural compounds. Flavonoids are natural polyphenolic molecules presenting varied biological activities and low toxicity. The flavonoid diosmin is a safe compound with good tolerability and low toxicity. This study evaluated the antinociceptive effect of diosmin in the sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain model. Male Swiss mice were submitted to CCI and 7 days after, diosmin at 1 or 10 mg/kg was administrated intraperitoneally. Mechanical (electronic analgesimeter) and thermal (hot plate) hyperalgesia were evaluated 1-24 h after treatment. The role of the NO/cGMP/PKG/KATP channel signaling pathway in the analgesic effect of diosmin was evaluated using the pretreatment with L-NAME (an inhibitor of NOS), ODQ (an inhibitor of soluble guanylate cyclase), KT5823 (an inhibitor of PKG), or glibenclamide (an ATP-sensitive K+ channels blocker). Single treatment with diosmin inhibited in a dose-dependent manner CCI-induced mechanical and thermal hyperalgesia by activating the NO/cGMP/PKG/KATP channel signaling pathway and inhibiting spinal cord cytokine (Il-1 beta and Il-33/St2) and glial cells activation (microglia-Iba-1, oligodendrocytes - Olig2) mRNA expression markers. Daily treatment during 7 days with diosmin inhibited CCI-induced mechanical and thermal hyperalgesia by inhibiting spinal cord cytokine (Il-1 beta, Tnf alpha, and Il-33/St2) and glial cells activation (astrocytes - Gfap, Iba-1, and Olig2) markers mRNA expression. In conclusion, diosmin inhibits neuropathic spinal cord nociceptive mechanisms suggesting this flavonoid as a potential therapeutic molecule to reduce nerve lesion-induced neuropathic pain. (C) 2017 Elsevier B.V. All rights reserved.
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