Neuroplasticity of sensory and sympathetic nerve fibers in a mouse model of a painful arthritic joint
Article first published online: 26 JUN 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 7, pages 2223–2232, July 2012
How to Cite
Ghilardi, J. R., Freeman, K. T., Jimenez-Andrade, J. M., Coughlin, K. A., Kaczmarska, M. J., Castaneda-Corral, G., Bloom, A. P., Kuskowski, M. A. and Mantyh, P. W. (2012), Neuroplasticity of sensory and sympathetic nerve fibers in a mouse model of a painful arthritic joint. Arthritis & Rheumatism, 64: 2223–2232. doi: 10.1002/art.34385
- Issue published online: 26 JUN 2012
- Article first published online: 26 JUN 2012
- Accepted manuscript online: 13 JAN 2012 11:48AM EST
- Manuscript Accepted: 10 JAN 2012
- Manuscript Received: 18 MAR 2011
- Department of Veterans Affairs
- Veterans Health Administration. Grant Number: Rehabilitation Research and Development Service grants O4380-I and A6707-R
- NIH. Grant Numbers: NS-23970, CA-154550, CA-157449
- Calhoun Fund for Bone Pain
Many forms of arthritis are accompanied by significant chronic joint pain. This study was undertaken to investigate whether there is significant sprouting of sensory and sympathetic nerve fibers in the painful arthritic knee joint and whether nerve growth factor (NGF) drives this pathologic reorganization.
A painful arthritic knee joint was produced by injection of Freund's complete adjuvant (CFA) into the knee joint of young adult mice. CFA-injected mice were then treated systemically with vehicle or anti-NGF antibody. Pain behaviors were assessed, and at 28 days following the initial CFA injection, the knee joints were processed for immunohistochemistry analysis using antibodies against calcitonin gene–related peptide (CGRP; sensory nerve fibers), neurofilament 200 kd (NF200; sensory nerve fibers), growth-associated protein 43 (GAP-43; sprouted nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), CD31 (endothelial cells), or CD68 (monocyte/macrophages).
In CFA-injected mice, there was a significant increase in the density of CD68+ macrophages, CD31+ blood vessels, and CGRP+, NF200+, GAP-43+, and TH+ nerve fibers in the synovium, as well as a significant increase in joint pain–related behaviors. None of these findings were observed in sham-injected mice. Administration of anti-NGF reduced these pain-related behaviors and the ectopic sprouting of nerve fibers, but had no significant effect on the increase in density of CD31+ blood vessels or CD68+ macrophages.
These findings demonstrate that ectopic sprouting of sensory and sympathetic nerve fibers occurs in the painful arthritic joint and may be involved in the generation and maintenance of arthritic pain.