Origins of skeletal pain: sensory and sympathetic innervation of the mouse femur

Although skeletal pain plays a major role in reducing the quality of life in patients suffering from osteoarthritis, Paget’s disease, sickle cell anemia and bone cancer, little is known about the mechanisms that generate and maintain this pain. To define the peripheral fibers involved in transmittin...

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Bibliographic Details
Published in:	Neuroscience Vol. 113; no. 1; pp. 155 - 166
Main Authors:	Mach, D.B, Rogers, S.D, Sabino, M.C, Luger, N.M, Schwei, M.J, Pomonis, J.D, Keyser, C.P, Clohisy, D.R, Adams, D.J, O’Leary, P, Mantyh, P.W
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-01-2002 Elsevier
Subjects:	Afferent Pathways Animals Biological and medical sciences bone Bone and Bones - chemistry Bone and Bones - innervation Bone Marrow - chemistry Bone Marrow - innervation Calcitonin Gene-Related Peptide - analysis Efferent Pathways Femur - chemistry Femur - innervation Fundamental and applied biological sciences. Psychology Immunohistochemistry Lectins - analysis Male marrow Mice Mice, Inbred C3H micro-computed tomography Nerve Fibers - chemistry Nerve Fibers, Myelinated - chemistry nerves Neurofilament Proteins - analysis Pain - metabolism Pain - pathology Pain - physiopathology periosteum Periosteum - chemistry Periosteum - innervation Plant Lectins Skeleton and joints Sympathetic Fibers, Postganglionic - chemistry Tyrosine 3-Monooxygenase - analysis Vertebrates: osteoarticular system, musculoskeletal system micro-computed tomography EDTA, ethylenediaminetetra-acetate μCT, micro-computed tomography ir, immunoreactive bone RT-97, neurofilament H TSA, tyramide signal amplification nerves marrow periosteum PBS, phosphate-buffered saline IB4, isolectin B4 TH, tyrosine hydroxylase immunohistochemistry CGRP, calcitonin gene-related peptide Osteoarticular system Vertebrata Femur Mammalia Pain Mouse Autonomic nervous system Innervation Rodentia Skeleton Bone Sympathetic nervous system
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Summary:	Although skeletal pain plays a major role in reducing the quality of life in patients suffering from osteoarthritis, Paget’s disease, sickle cell anemia and bone cancer, little is known about the mechanisms that generate and maintain this pain. To define the peripheral fibers involved in transmitting and modulating skeletal pain, we used immunohistochemistry with antigen retrieval, confocal microscopy and three-dimensional image reconstruction of the bone to examine the sensory and sympathetic innervation of mineralized bone, bone marrow and periosteum of the normal mouse femur. Thinly myelinated and unmyelinated peptidergic sensory fibers were labeled with antibodies raised against calcitonin gene-related peptide (CGRP) and the unmyelinated, non-peptidergic sensory fibers were labeled with the isolectin B4 ( Bandeira simplicifolia). Myelinated sensory fibers were labeled with an antibody raised against 200-kDa neurofilament H (clone RT-97). Sympathetic fibers were labeled with an antibody raised against tyrosine hydroxylase. CGRP, RT-97, and tyrosine hydroxylase immunoreactive fibers, but not isolectin B4 positive fibers, were present throughout the bone marrow, mineralized bone and the periosteum. While the periosteum is the most densely innervated tissue, when the total volume of each tissue is considered, the bone marrow receives the greatest total number of sensory and sympathetic fibers followed by mineralized bone and then periosteum. Understanding the sensory and sympathetic innervation of bone should provide a better understanding of the mechanisms that drive bone pain and aid in developing therapeutic strategies for treating skeletal pain.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0306-4522 1873-7544
DOI:	10.1016/S0306-4522(02)00165-3