Fructooligosaccharide ameliorates inflammation-induced chronic pain via deactivation of LPS/TLR-4/NF-kappaB p65/TNF-alpha/IL-6 pathway in estrogen-deficient rats
Inflammopharmacology. 2026 Feb 14. doi: 10.1007/s10787-026-02123-7. Online ahead of print.
ABSTRACT
Estrogen deficiency during menopause is linked to increased chronic pain and inflammation, partly due to gut dysbiosis and systemic release of lipopolysaccharides (LPS). These LPS molecules activate TLR-4 receptors, triggering inflammatory cascades. While 17β-estradiol is a commonly used hormone replacement therapy, poses serious side effects. Earlier studies reported that fructooligosaccharide (FOS) modulates gut microbiota and diminishes LPS release. However, its role in attenuating chronic pain through the LPS/TLR-4/NF-κB p65/TNF-α/IL-6 pathway remains underexplored. We aimed that FOS may attenuate estrogen deficiency-induced chronic pain and associated inflammation via inhibiting LPS/TLR-4/NF-κB p65/TNF-α/IL-6 pathway. Female Sprague Dawley rats were bilaterally ovariectomized (OVX) to stimulate postmenopausal conditions, and further treated orally with FOS (25, 50 and 100 mg/kg) for 28 days. Pain sensitivity was assessed using thermal and mechanical nociception. Oxidative stress markers and ELISA (serum LPS and NF-κB p65) were measured in the brain and colon. Inflammation was measured via analysing expression of TLR-4, TNF-α, and IL-6 genes through RT-PCR. FOS (50 and 100 mg/kg) treatment significantly attenuated pain sensitivity through improving thermal and mechanical hyperalgesia. FOS exerts a potent antioxidant via reducing oxidative stress in both the colon and brain. FOS (50 and 100 mg/kg) also attenuates inflammation via suppressing serum LPS levels, and downregulates the expression of TLR-4, NF-κB p65, TNF-α, and IL-6 in both colon and brain. FOS exhibits potent anti-inflammatory and analgesic effects by deactivating the LPS/TLR-4/NF-κB p65/TNF-α/IL-6 pathway, reducing oxidative stress, and restoring the gut-brain axis, supporting its potential as a gut-targeted therapy for postmenopausal chronic pain and inflammation.
PMID:41689747 | DOI:10.1007/s10787-026-02123-7