title: Pain perception in knees with circumscribed cartilage lesions is associated with intra-articular IGF-1 expression.
abstract: BACKGROUND
  Circumscribed cartilage defects are considered as prearthritic lesions and lead to differential intra-articular cytokine expression. Mechanisms of associated pain development and influence of smoking behavior are not yet fully understood in humans.
  
  
  OBJECTIVE
  This study aimed to reveal relations between synovial cytokine levels in knees with circumscribed cartilage defects and pain sensation.
  
  
  METHODS
  Descriptive laboratory study.
  
  
  METHODS
  In a clinical trial, knee lavage fluids of 42 patients with circumscribed cartilage lesions treated by either microfracturing (n = 19) or by autologous chondrocyte implantation (n = 23) and fluids of 5 healthy control individuals were prospectively collected. Preoperative knee pain was evaluated according to frequency and strength; subjective knee function was assessed using a visual analog scale and the International Knee Documentation Committee (IKDC) score. Synovial concentrations of aggrecan, insulin-like growth factor (IGF)-I, basic fibroblast growth factor (bFGF), interleukin (IL)-1β, bone morphogenetic protein (BMP)-2, and BMP-7 were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Pain strength showed a highly significant association with intra-articular IGF-1 levels (ρ = .48, P < .01), but no correlation with synovial concentrations of aggrecan, bFGF, IL-1β, BMP-2, and BMP-7. Although pain strength and frequency demonstrated a statistically significant relationship, no substantial association between pain frequency and any of the examined cytokine levels was found. Intra-articular IGF-1 concentrations significantly correlated with the area of cartilage damage (ρ = .35, P < .02); the other investigated cytokines failed to show this association. Neither of the determined intra-articular mediators demonstrated statistically significant correlations with subjective knee function or IKDC score. Only intra-articular concentrations of IGF-1 and BMP-2 statistically significantly correlated with age; total protein content was negatively associated with body mass index (P < .05). In smokers, synovial expression of total protein content, IGF-1, and bFGF was significantly diminished compared to nonsmokers (P < .05).
  
  
  CONCLUSIONS
  Insulin-like growth factor-I is present in knees with circumscribed cartilage lesions in a size-dependent manner. IGF-1 levels correlated with indicators of pain perception; smoking negatively influenced synovial cytokine expression related to cartilage metabolism, but pain perception was not altered.
authors: Department of Orthopaedic Surgery, University of Freiburg Medical Center, Freiburg im Breisgau, Germany. hagen.schmal@freenet.de
authors: Hagen
authors: H
authors: Schmal
authors: Philipp
authors: P
authors: Niemeyer
authors: Norbert P
authors: NP
authors: Südkamp
authors: Ulrike
authors: U
authors: Gerlach
authors: David
authors: D
authors: Dovi-Akue
authors: Alexander T
authors: AT
authors: Mehlhorn