Genistein, a natural phytoestrogen from soy relieves, neuropathic pain following

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J Neurochem. 2008 Aug 8.

GENISTEIN, A NATURAL PHYTOESTROGEN FROM SOY, RELIEVES NEUROPATHIC

PAIN FOLLOWING CHRONIC CONSTRICTION SCIATIC NERVE INJURY IN MICE:

ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIVITY.

Valsecchi AE, Franchi S, Panerai AE, Sacerdote P, Trovato AE,

Colleoni M.

Department of Pharmacology, Chemotherapy and Medical Toxicology,

University of Milan, Via Vanvitelli 32, 20129 Milano, Italy.

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

ERbeta 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 ERbeta antagonist

prevented both its anti-allodynic and anti-hyperalgesic action,

whereas a specific ERalpha antagonist was ineffective and a non-

selective ER antagonist only reversed the anti-allodynic effect,

suggests the involvement of ERbeta.

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-small

ka, Cyrillicappa B, nitric oxide system and pro-inflammatory cytokine

over-activation.

Taken together, our results suggest that genistein could ameliorate

painful neuropathy by multiple mechanisms.