Sprouting of sensory nerve fibers in the tumor bearing bone. Confocal images of non-decalcified whole mount preparations of the femoral periosteum from sham (A) or sarcoma + vehicle mice (B, C) immunostained with calcitonin gene-related peptide (CGRP), a marker of peptide-rich C-fibers and some A-delta sensory nerve fibers. Note the increased density and disorganized appearance of CGRP+ nerve fibers (in red) in the periosteum of the tumor-injected femur (B, C) compared to the periosteum of sham animals (A). This pathological sprouting pattern is found in the periosteum near viable tumor/stromal cells (C). Confocal images of periosteum were acquired from whole mount preparations and projected from 280 optical sections at 0.25 μm intervals with a 40x objective.