Fig. 4

Distribution of CGRP-positive nerve fibers in IFP and L4 DRG. a Representative immunohistochemical images of the knee joint at 28 days after the injection of MIA. Arrowheads in red indicate CGRP-positive nerve fibers. b Representative images of L4 DRG at day 28 post-MIA injection. The red signal indicates neuronal cell bodies projected from the knee joint (left column, FG). Neural cells positive for CGRP are indicated in green (middle column). Merged images are shown in the right column. Arrows in white indicate the CGRP-positive nerve cells projected from the knee joint. c, d Differences in innervation density between the MIA and control sides. Ten different areas of 0.01 mm² were randomly selected in the parenchymal region of IFP in each section. CGRP-positive nerve fibers > 0.03 mm were counted. There were 6 samples at each time point and 2 sections were randomly selected in each sample. Data are represented as mean and SD values. e Differences in innervation density between ipsilateral and contralateral indicated in (c) and (d) were calculated in each time point (innervation density of MIA subtracted by innervation density of control) and plotted. f, g The percentage of CGRP-positive neurons among the FG-labeled neurons. There were 6 samples in each time point. Four sections were randomly selected from each sample and the mean ± SD values were recorded (n = 6). Asterisks indicate statistically significant differences. h Differences in innervation density between ipsilateral and contralateral indicated in (f) and (g) were calculated in each time point (innervation density of MIA subtracted by innervation density of control) and plotted. CGRP, calcitonin gene-related peptide; DRG, dorsal root ganglion; FG, fluorogold; IFP, infrapatellar fat pad; MIA, monoiodo-acetic acid