Figure 3.

Capsaicin-induced angiogenesis was partially inhibited by the administration of each receptor antagonist, and coadministration of BIBN1096BS and SR140333 completely blocked capsaicin-enhanced angiogenesis. (A) Endothelial PCNA indices of rat synovia from knees injected with 0.5% capsaicin were significantly reduced by either the SP receptor antagonist SR140333 (bar 3) or by the CGRP receptor antagonist BIBN4096BS (bar 4) when compared with the positive control capsaicin alone, bar 2; P < 0.001 for both treatments. When given in combination, the two receptor antagonists (bar 5) reduced the rise in PCNA index attributable to capsaicin to the same level as saline controls; P > 0.05. PCNA index was defined as the percentage of endothelial cell nuclei positive for PCNA. Data shown are means ± SD; n = 6 rats per group. (B). Knee joint diameters corresponding to the same groups in (A), showing significant inhibition of joint swelling by SR140333, either alone (bar 2, P < 0.01) or in combination with BIBN4096BS (bar 5, P < 0.01). The change in knee diameter from baseline to 24 h is shown in mm, as means ± SD; n = 6 rats per group.. In each panel, the negative control (bar 1) represents data from synovia 24 h after intra-articular saline injection accompanied by i.v. injection of the CGRP receptor antagonist BIBN4096BS and i.p. injection of the SP receptor antagonist SR140333. The positive control (bar 2) represents data from synovia 24 h after intra-articular injection of capsaicin in the absence of either antagonist. Capsaicin is believed to release endogenous CGRP and SP from sensory nerves in the synovium. All groups of rats (bars 2–5), with the exception of saline controls (bar 1), were treated with capsaicin.