Genistein, a natural phytoestrogen from soy, relieves neuropathic pain following chronic constriction sciatic nerve injury in mice: Anti-inflammatory and antioxidant activity

Anna Elisa Valsecchi, Silvia Franchi, Alberto Emilio Panerai, Paola Sacerdote, Anna Elisa Trovato, Mariapia Colleoni

Research output: Contribution to journalArticlepeer-review

Abstract

There is great interest in soy isoflavones as alternatives to endogenous estrogens not only in hormonal pathologies, but also in inflammatory, neurodegenerative diseases, and pain. We investigated the effect of the isoflavone genistein on neuropathic pain. Genistein binds estrogen receptors (ER) with higher affinity for the ERβ particularly expressed in neuronal and immune cells. Neuropathy was induced in mice by means of chronic sciatic nerve constriction, and the subcutaneous administration of genistein from the third day after the lesion reversed pain hypersensitivity in a time- and dose-dependent manner. This effect may have been due to the activation of classical nuclear receptor and/or anti-oxidant, anti-inflammatory, and immunomodulating properties of genistein. The fact that a specific ERβ antagonist prevented both its anti-allodynic and anti-hyperalgesic action, whereas a specific ERα antagonist was ineffective and a non-selective ER antagonist only reversed the anti-allodynic effect, suggests the involvement of ERβ. Antioxidant effects are also involved as the anti-nociceptive dose reversed the increase in reactive oxygen species and malondialdehyde in injured paw tissues, and increased the activity of anti-oxidant enzymes. The phytoestrogen had immunomodulatory and anti-inflammatory activities as it reduced peripheral and central nuclear factor-κB, nitric oxide system and pro-inflammatory cytokine over-activation. Taken together, our results suggest that genistein could ameliorate painful neuropathy by multiple mechanisms.

Original languageEnglish
Pages (from-to)230-240
Number of pages11
JournalJournal of Neurochemistry
Volume107
Issue number1
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Chronic constriction injury
  • Estrogen receptor β
  • Genistein
  • Mouse
  • Neuropathic pain
  • Soy phytoestrogen

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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