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

• Published in: Journal of neurochemistry 2008-10, Vol.107 (1), p.230-240
• Main Authors: Valsecchi, Anna Elisa, Franchi, Silvia, Panerai, Alberto Emilio, Sacerdote, Paola, Trovato, Anna Elisa, Colleoni, Mariapia
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Biochemistry; Biological and medical sciences; Cellular biology; chronic constriction injury; Chronic Disease - drug therapy; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Disease Models, Animal; Dose-Response Relationship, Drug; estrogen receptor β; Estrogens; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Ganglia, Spinal - physiopathology; genistein; Genistein - pharmacology; Genistein - therapeutic use; Glycine max - chemistry; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - physiopathology; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Injuries of the nervous system and the skull. Diseases due to physical agents; Ligation; Male; Medical sciences; Mice; Mice, Inbred C57BL; mouse; Nervous system (semeiology, syndromes); Neurology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; neuropathic pain; Nociceptors - drug effects; Nociceptors - metabolism; Nociceptors - physiopathology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pain management; Peripheral Nervous System Diseases - drug therapy; Peripheral Nervous System Diseases - metabolism; Peripheral Nervous System Diseases - physiopathology; Phytoestrogens - pharmacology; Phytoestrogens - therapeutic use; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Receptors, Estrogen - drug effects; Receptors, Estrogen - metabolism; Sciatic Neuropathy - drug therapy; Sciatic Neuropathy - metabolism; Sciatic Neuropathy - physiopathology; soy phytoestrogen; Soy products; Traumas. Diseases due to physical agents; Treatment Outcome
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05614.x

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.