Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur
Section snippets
Experimental animals
Experiments were performed on 43 C3H/HeJ mice (36 adult male C3H/HeJ mice for immunohistochemistry, three adult male C3H/HeJ mice for volumetric analysis, and four 7-day-old neonates for testing antibody antigenicity) (Jackson Laboratories, Bar Harbor, ME, USA). All the mice except for the neonates were 6–7 weeks old and weighed 20–25 g. The mice were housed in accordance with National Institutes of Health guidelines and kept in a vivarium maintained at 22°C with a 12-h alternating light–dark
Innervation pattern and distribution of CGRP immunoreactive nerve fibers in the periosteum, mineralized bone and bone marrow
Thinly myelinated or unmyelinated peptidergic sensory fibers were labeled with an antibody raised against CGRP. CGRP immunoreactive (CGRP-ir) nerve fibers were found throughout the periosteum, which is composed mainly of fibrous connective tissue approximately 30–60 μm thick and envelops the entire outer surface of mineralized bone except at the points of ligament and tendon insertion (Marieb and Mallat, 1997). When the periosteum was viewed in a whole mount preparation, CGRP-ir nerve fibers
Sensory and sympathetic innervation of normal bone
In the present report, we show that in addition to CGRP and TH expressing fibers that innervate the mineralized bone, bone marrow, and periosteum, there is also a population of myelinated primary afferent sensory neurons fibers which express RT-97 that innervate the bone. The presence of both CGRP-ir and RT-97-ir fibers suggests that the mineralized bone, the bone marrow and the periosteum receive innervation from both unmyelinated and myelinated sensory neurons, which would presumably include
Acknowledgements
This work was supported by NIH Grants NINDS NS23970, NIDA 11986, NIDCR Training Grant DEO7288 (D.B.M.), DE00270 (M.C.S.), AR43595, a Merit Review from the Veterans Administration and a grant from the Supercomputing Institute for Digital Simulation and Advanced Computation at the University of Minnesota.
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