Sprouting and formation of neuroma-like structures in chronic bone pain. Sarcoma tumor cells expressing green fluorescent protein (green) induce a marked sprouting and neuroma formation of CGRP+ sensory nerve fibers (red) that innervate the bone (white). These nerve fibers detect and transmit painful stimuli from periphery to the central nervous system. A) In sham bones, CGRP+ nerve fibers that are present in the bone appear as single nerve fibers with a liner and homogenous morphology. B) As cancer cells proliferate and grow in bone, these induce significant bone remodeling (pitted appearance) as well as a highly pathological sprouting and formation of neuroma-like structures by sensory and sympathetic nerve fibers which in other conditions drives chronic pain. Confocal images from periosteal whole preparations were acquired and overlapped on a three dimensional image of the mouse femur obtained by microcomputed tomography. Images were rendered courtesy of Marvin Landis (University Information Technology Services, University of Arizona).