The Changing Sensory and Sympathetic Innervation of the Young, Adult and Aging Mouse Femur

Stephane R Chartier,Stefanie A.T Mitchell,Lisa A Majuta,Patrick W Mantyh

doi:10.1016/j.neuroscience.2018.01.047

Stephane R Chartier, Stefanie A.T Mitchell + Show 2 more

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https://doi.org/10.1016/j.neuroscience.2018.01.047

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Journal: Neuroscience	Publication Date: Feb 10, 2018
Citations: 98	License type: cc-by

Affiliation: University of Arizona

Abstract

Although bone is continually being remodeled and ultimately declines with aging, little is known whether similar changes occur in the sensory and sympathetic nerve fibers that innervate bone. Here, immunohistochemistry and confocal microscopy were used to examine changes in the sensory and sympathetic nerve fibers that innervate the young (10 days post-partum), adult (3 months) and aging (24 months) C57Bl/6 mouse femur. In all three ages examined, the periosteum was the most densely innervated bone compartment. With aging, the total number of sensory and sympathetic nerve fibers clearly declines as the cambium layer of the periosteum dramatically thins. Yet even in the aging femur, there remains a dense sensory and sympathetic innervation of the periosteum. In cortical bone, sensory and sympathetic nerve fibers are largely confined to vascularized Haversian canals and while there is no significant decline in the density of sensory fibers, there was a 75% reduction in sympathetic nerve fibers in the aging vs. adult cortical bone. In contrast, in the bone marrow the overall density/unit area of both sensory and sympathetic nerve fibers appeared to remain largely unchanged across the lifespan. The preferential preservation of sensory nerve fibers suggests that even as bone itself undergoes a marked decline with age, the nociceptors that detect injury and signal skeletal pain remain relatively intact.

Highlights

The study of chronic skeletal pain most commonly focuses on diseases such as osteoarthritis, low back pain and fragility fractures which are due in large part to the agerelated decline in the mass, quality and strength of the skeleton (Heaney, Abrams et al 2000, Melton, Johnell et al 2004, Mantyh 2014)
The periosteum can be divided into two distinct regions, the outer fibrous layer and the inner cambium layer
In addition to the decline in the thickness of the cambium layer with age, we observed a decline in the thickness of the fibrous layer as well between the young and adult periosteum, 76±2 vs. 24±1 microns, respectively

Summary

Introduction

The study of chronic skeletal pain most commonly focuses on diseases such as osteoarthritis, low back pain and fragility fractures which are due in large part to the agerelated decline in the mass, quality and strength of the skeleton (Heaney, Abrams et al 2000, Melton, Johnell et al 2004, Mantyh 2014). An interesting but largely unanswered question is whether as the mass, quality and strength of bone and cartilage decline with age (Exton-Smith, Millard et al 1969, Woolf and Pfleger 2003), do the nerves that innervate the skeleton undergo a marked decline?. Previous studies have suggested that many antibodies that work well in the non-calcified tissues frequently showed marked loss of immunostaining when subjected to the decalcification process (Arnold 1988, Shi, Key et al 1991, Schulze, Witt et al 1997, Hayat 2002, Mach, Rogers et al 2002, Mantyh, JimenezAndrade et al 2010, Chartier, Thompson et al 2014)

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