• Media type: E-Article
  • Title: Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells
  • Contributor: Ma, Junxuan; Häne, Surya; Eglauf, Janick; Pfannkuche, Judith; Soubrier, Astrid; Li, Zhen; Peroglio, Marianna; Hoppe, Sven; Benneker, Lorin; Lang, Gernot; Wangler, Sebastian; Alini, Mauro; Creemers, Laura B.; Grad, Sibylle; Häckel, Sonja
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: European Spine Journal
  • Language: English
  • DOI: 10.1007/s00586-023-07672-x
  • ISSN: 0940-6719; 1432-0932
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1β. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 μM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1β treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Cxb can inhibit PGE-2 production in hAFCs in an IL-1β-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.</jats:p> </jats:sec>