title: The Effect of Substance P on an Intervertebral Disc Rat Organ Culture Model.
abstract: METHODS
  Laboratory study.
  
  
  OBJECTIVE
  Evaluate the effect of substance P (SP) on an intervertebral disc rat organ culture model.
  
  
  BACKGROUND
  Monolayer cell experiments have demonstrated that exposure intervertebral disc tissue cells to SP leads to upregulation in inflammatory cytokine expression; however, this has not been evaluated in a more complex organ culture model.
  
  
  METHODS
  Forty-eight intervertebral discs from eight rats were used in an organ culture model. Intervertebral discs were divided into three groups: control, SP-treated group, and a group treated with an SP antagonist followed by SP. Cytokine antibody array was used to quantify expression patterns, which were confirmed using ELISA and real-time polymerase chain reaction.
  
  
  RESULTS
  The cytokine array demonstrated a 3.40 ±  0.59-fold increase in interleukin 6 (IL-6) expression in the SP group (P = 0.004), and the effect of SP was mitigated by the SP antagonist (P = 0.03). These results were verified as ELISA demonstrated a significant difference in the IL-6 level between the control group and SP group (0.73 vs. 5.80 ng/mL, P < 0.001), and there was a significant difference in the IL-6 level between the SP and the SP antagonist group (5.80 vs. 4.02 ng/mL, P = 0.01). Similarly, the real-time polymerase chain reaction demonstrated that the discs treated with SP had a 4.77-fold increase in IL-6 levels (P = 0.01) compared to controls, and a significantly greater increase in IL-6 levels between the intervertebral discs in the SP group and those in the SP antagonist group versus control (4.77 vs. 1.57, P = 0.02).
  
  
  CONCLUSIONS
  SP lead to the activation of an inflammatory pathway by increasing expression of IL-6 in an intervertebral disc organ culture model. These results provide evidence that SP may be an important factor in the link between intervertebral disc degeneration and low back pain.
  
  
  METHODS
  N/A.
authors.affiliation: Rothman Institute, Philadelphia, PA.|Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: John D
authors.initials: JD
authors.lastname: Koerner
authors.affiliation: Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Dessislava Z
authors.initials: DZ
authors.lastname: Markova
authors.affiliation: Rothman Institute, Philadelphia, PA.|Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Schroeder
authors.affiliation: Rothman Institute, Philadelphia, PA.|Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Rihn
authors.affiliation: Rothman Institute, Philadelphia, PA.|Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Hilibrand
authors.affiliation: Rothman Institute, Philadelphia, PA.|Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Vaccaro
authors.affiliation: Rothman Institute, Philadelphia, PA.|Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: D Greg
authors.initials: DG
authors.lastname: Anderson
authors.affiliation: Rothman Institute, Philadelphia, PA.|Department of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Kepler
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D013373:Substance P / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D013373:Substance P