Spinal Nrf2 translocation may inhibit neuronal NF ‐κB activation and alleviate allodynia in a rat model of bone cancer pain

This study aimed to test the hypothesis that BCP induces the transfer of Nrf2 from the cytoplasm to the nucleus and further promotes nuclear transcription to activate heme oxygenase-1 (HO-1) and inhibit the activation of nuclear factor-kappa B (NF- κB) signalling, ultimately regulating the neuroinflammatory response. Von-Frey was used for behavioural analysis in BCP rats, while western blotting, real-time quantitative PCR (RT-PCR), and enzyme-linked immunosorbent assay (ELISA) were used to detect molecular expression changes, and immunofluore scence was used to detect cellular localization. We demonstrated that BCP induced increased Nrf2 nuclear protein expression with decreased cytoplasmic protein expression in the spinal cord. Further increases in Nrf2 nuclear protein expression can alleviate hyperalgesia and activate HO-1 to inhibit t he expression of NF-κB nuclear protein and inflammatory factors. Strikingly, intrathecal administration of the corresponding siRNA reversed the above effects. In addition, the results of double immune labelling revealed that Nrf2 and NF-κB were coexpressed in spinal cord neurons of BCP rats. In su mmary, these findings suggest that the entry of Nrf2 into the nucleus promotes the expression of HO-1, inhibiting activation of the NF-κB signalling pathway, reducing neuroinflammation, and ultimately exerting an antinociceptive effect.
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research