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Spinal Nrf2 translocation may inhibit neuronal NF-κB activation and alleviate allodynia in a rat model of bone cancer pain.
Fu, Jie; Ni, Chaobo; Ni, Hua-Dong; Xu, Long-Sheng; He, Qiu-Li; Pan, Huan; Huang, Dong-Dong; Sun, Yan-Bao; Luo, Ge; Liu, Ming-Juan; Yao, Ming.
  • Fu J; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Ni C; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Ni HD; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Xu LS; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • He QL; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Pan H; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Huang DD; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Sun YB; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Luo G; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Liu MJ; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
  • Yao M; Department of Anesthesiology and Pain Research Center, The First Hospital of Jiaxing or The Affiliated Hospital of Jiaxing University, Jiaxing, China.
J Neurochem ; 158(5): 1110-1130, 2021 09.
Article en En | MEDLINE | ID: mdl-34254317
ABSTRACT
Bone cancer pain (BCP) is a clinical pathology that urgently needs to be solved, but research on the mechanism of BCP has so far achieved limited success. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) has been shown to be involved in pain, but its involvement in BCP and the specific mechanism have yet to be examined. 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 rats with BCP, whereas western blotting, real-time quantitative PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect molecular expression changes, and immunofluorescence 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 the 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 rats with BCP. In summary, 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 anti-nociceptive effect.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Médula Espinal / Neoplasias Óseas / FN-kappa B / Factor 2 Relacionado con NF-E2 / Dolor en Cáncer / Hiperalgesia Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2021 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Médula Espinal / Neoplasias Óseas / FN-kappa B / Factor 2 Relacionado con NF-E2 / Dolor en Cáncer / Hiperalgesia Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Año: 2021 Tipo del documento: Article