title: Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue that can be limited by a COX-2-specific inhibitor.
abstract: In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the inflammation. Since herniated tissue swells, we investigated whether this simple mechanobiological stimulus alone could provoke an inflammatory response that could cause pain. Furthermore, we investigated whether sustained-release cyclooxygenase-2 (COX2) inhibitor would be beneficial in such conditions. Healthy bovine NP explants were allowed to swell freely or confined. The swelling explants were treated with Celecoxib, applied either as a bolus or in sustained-release. Swelling explants produced elevated levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2 ) for 28 days, while confined explants did not. Both a high concentration bolus and 10 times lower concentration in sustained release completely inhibited PGE2 production, but did not affect IL-6 production. Swelling of NP tissue, without the inflammatory system response, can trigger cytokine production and Celecoxib, even in bolus form, may be useful for pain control in extruded disc herniation.
authors.affiliation: Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: van Dijk
authors.affiliation: Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Potier
authors.affiliation: DSM Biomedical B.V., Geleen, the Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van DIjk
authors.affiliation: TNO-The Netherlands Organization for Applied Scientific Research, Eindhoven, the Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Langelaan
authors.affiliation: TNO-The Netherlands Organization for Applied Scientific Research, Eindhoven, the Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Papen-Botterhuis
authors.affiliation: Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Keita
authors.initials: K
authors.lastname: Ito
mesh_terms: D000818:Animals; D002417:Cattle; D000068579:Celecoxib / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007403:Intervertebral Disc / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013314:Stress, Mechanical; D046509:Tissue Culture Techniques
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D000068579:Celecoxib; D015232:Dinoprostone
keywords: disc herniation; explant culture; inflammation; regenerative therapy; sustained release