Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium

Ann Rheum Dis. 2005 Jan;64(1):13-20. doi: 10.1136/ard.2003.016154.


Objective: To investigate the correlation between density of nerve fibres and the presence of BDNF(+) cells.

Methods: Densities of nerve fibres and BDNF(+) cells were detected by quantitative immunohistochemistry in fresh synovial tissue from 52 patients with RA, 59 with OA, and 26 controls (Co). BDNF was also detected by in situ hybridisation.

Results: Sympathetic nerve fibre density was similar in Co and OA but markedly reduced in RA (p = 0.002), whereas density of substance P positive (SP(+)) sensory nerve fibres was lower in OA than in Co and RA (p = 0.002). The ratio of sympathetic/SP(+) sensory nerve fibre density was highest in OA and Co, followed by RA. The correlation between density of sympathetic nerve fibres and SP(+) sensory nerve fibres in OA (R = 0.425, p = 0.001) was strongly positive, had a positive trend in Co (R = 0.243, NS), but was negative in RA (R = -0.292, p = 0.040). In RA and OA tissue the density of BDNF(+) cells was high in sublining areas but markedly lower in Co (p = 0.001). BDNF(+) cell density correlated positively with the ratio of sympathetic/SP(+) sensory nerve fibre density in Co (R = 0.433, p = 0.045) and in OA (R = 0.613, p = 0.015), but not in RA (R = 0.101, NS). Immunohistochemical double staining demonstrated that some macrophages and fibroblasts were positive for BDNF.

Conclusions: The correlation of density of SP(+) sensory with sympathetic nerve fibres was positive in Co and OA but negative in RA. BDNF may have a stimulatory role on growth of sympathetic in relation to SP(+) sensory nerve fibres in Co and OA, but not in RA.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Fibers / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • Brain-Derived Neurotrophic Factor / analysis*
  • Female
  • Fibroblasts / chemistry
  • Humans
  • Immunoenzyme Techniques
  • Macrophages / chemistry
  • Male
  • Middle Aged
  • Nerve Fibers / pathology
  • Osteoarthritis, Knee / metabolism
  • Osteoarthritis, Knee / pathology
  • Synovial Membrane / chemistry
  • Synovial Membrane / innervation*
  • Synovial Membrane / pathology


  • Brain-Derived Neurotrophic Factor