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Ann Rheum Dis. Jan 2005; 64(1): 13–20.
PMCID: PMC1755208

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


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.

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Figures and Tables

Figure 1
 Representative immunohistochemistry of substance P (SP) positive sensory nerve fibres and sympathetic tyrosine hydroxylase (TH) positive nerve fibres. Note the typical juxtaposition of TH positive fibres and the structure of an artery (arrow ...
Figure 2
 Density of sympathetic and SP+ sensory nerve fibres in control subjects (Co), patients with OA, and RA. (A) Density of SP+ sensory nerve fibres; (B) density of sympathetic TH+ nerve fibres; and (C) ratio of density of sympathetic/SP+ sensory ...
Figure 3
 Interrelation between density of sympathetic TH+ nerve fibres and density of SP+ sensory nerve fibres in (A) control subjects (Co); (B) patients with OA; and (C) patients with RA. The linear regression line and its Pearson correlation coefficient ...
Figure 4
 Immunohistochemistry of BDNF in synovial tissue. (A) Synovial tissue from a control subject without an inflammatory condition (Co), a patient with OA, and a patient with RA stains positive for BDNF. APAAP staining was used. (B) BDNF in situ ...
Figure 5
 Density of BDNF+ cells in control subjects (Co), patients with OA, and patients with RA. Values of p for comparison of group medians are given.
Figure 6
 Interrelation of the density of BDNF+ cells and the ratio of the density of sympathetic TH+ nerve fibres/the density of SP+ sensory nerve fibres in (A) control subjects (Co); (B) patients with OA; and (C) patients with RA. The linear regression ...

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