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Chem Biol Interact. 2017 Aug 1;273:180-189. doi: 10.1016/j.cbi.2017.06.014. Epub 2017 Jun 15.

Diosmin reduces chronic constriction injury-induced neuropathic pain in mice.

Author information

1
Department of General Pathology, Biological Sciences Center, Londrina State University, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, 86057-970 Londrina, Parana, Brazil.
2
Department of Pharmacology, Biological Sciences Center, Londrina State University, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, 86057-970 Londrina, Parana, Brazil.
3
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto 14049-900, São Paulo, Brazil.
4
Department of Pharmaceutical Sciences, University Hospital (Health Science Centre), Londrina State University, Av. Robert Koch, 60, 86038-350 Parana, Brazil.
5
Department of General Pathology, Biological Sciences Center, Londrina State University, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, 86057-970 Londrina, Parana, Brazil. Electronic address: waverri@uel.br.

Abstract

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-1β 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-1β, Tnfα, 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.

KEYWORDS:

Flavonoids; Hyperalgesia; Neuropathy; Oxidative stress

PMID:
28625489
DOI:
10.1016/j.cbi.2017.06.014
[Indexed for MEDLINE]
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