Soy isoflavone prevents chronic inflammatory pain in estrogen-deprived rats by ER-β-dependent deactivation of LPS/TLR-4/NFκB/p65/TNF-α/IL-6 pathway.

Estrogen, a steroid hormone, maintains women's physiology. Estrogen deficiency increases inflammation and associated central and peripheral pain hypersensitivity by raising pro-inflammatory cytokines & oxidative stress. 17β-estradiol is a well-known drug used to treat postmenopausal central and peripheral pain, but it causes numerous side effects. However, safer therapies are urgently needed to prevent postmenopausal complications. The current study aimed to investigate the therapeutic potential of soy isoflavone (SIF) in reducing central and peripheral pain hypersensitivity in ovariectomized (OVX) rats. First, rats were estrogen-deprived, and then SIF (40, 80, & 160 mg/kg) was given. Various behavioural, biochemical, and molecular parameters were assessed in the colon and brain. SIF significantly reduces serum lipopolysaccharide (LPS) levels and downregulates toll-like receptor-4 (TLR-4) gene expression. SIF decreases nuclear factor kappa B (NFκB/p65), C-reactive protein (CRP), and downregulates tumor necrosis factor-alpha (TNF-α) & interleukin-6 (IL-6) gene expression. SIF restores thermal and mechanical pain thresholds. SIF selectively activates the estrogen receptor-beta (ER-β) gene and further restores serum estradiol levels. Thus, SIF prevents chronic inflammatory pain in OVX rats via ER-β-dependent deactivation of the LPS/TLR-4/NFκB/p65/TNF-α/IL-6 pathway.