Figure 6

Intraarticular injection of CFA induces nerve sprouting and formation of neuroma-like structures in the periosteum. (A) Schematic of the frontal view of a cross-sectioned mouse knee joint illustrating the periosteal region from which the confocal images were obtained (red square). Representative confocal images of CGRP⁺ and NF200⁺ sensory nerve fibers (yellow/orange), TH sympathetic nerve fibers (yellow/orange), and DAPI labeled nuclei (blue) in 20 μm-thick knee sections from vehicle-injected (B, D, F, H) and CFA-injected (C, E, G, I) mice. In vehicle-injected mice, a low-level, regular pattern of innervation by CGRP⁺, NF200⁺, and TH⁺ nerve fibers is observed in the synovial space of the knee joint. Twenty-eight days after the initial CFA injection, a significant number of CGRP⁺, NF200⁺, and TH⁺ nerve fibers have sprouted and have a disorganized appearance as compared with vehicle-injected mice. Furthermore, a formation of neuroma-like structures by NF200⁺ nerve fibers was seen in the femoral periosteum of the geriatric mice injected with CFA (I).