Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice

Persistent Link:
http://hdl.handle.net/10150/610392
Title:
Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice
Author:
Jimenez-Andrade, Juan; Mantyh, Patrick
Affiliation:
Department of Pharmacology, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA; Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Reynosa, Reynosa, 88740, México; Arizona Cancer Center, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA; Research Service, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417, USA
Issue Date:
2012
Publisher:
BioMed Central
Citation:
Jimenez-Andrade and Mantyh Arthritis Research & Therapy 2012, 14:R101 http://arthritis-research.com/content/14/3/R101
Journal:
Arthritis Research & Therapy
Rights:
© 2012 Mantyh et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
INTRODUCTION:Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic nerve sprouting; however, neuroplasticity is generally thought to be greater in young versus old nerves. Here we explore whether sensory and sympathetic nerve fibers can undergo a significant ectopic nerve remodeling in the painful arthritic knee joint of geriatric mice.METHODS:Vehicle (saline) or complete Freund's adjuvant (CFA) was injected into the knee joint of 27- to 29-month-old female mice. Pain behaviors, macrophage infiltration, neovascularization, and the sprouting of sensory and sympathetic nerve fibers were then assessed 28 days later, when significant knee-joint pain was present. Knee joints were processed for immunohistochemistry by using antibodies raised against CD68 (monocytes/macrophages), PECAM (endothelial cells), calcitonin gene-related peptide (CGRP; sensory nerve fibers), neurofilament 200 kDa (NF200; sensory nerve fibers), tyrosine hydroxylase (TH; sympathetic nerve fibers), and growth-associated protein 43 (GAP43; nerve fibers undergoing sprouting).RESULTS:At 4 weeks after initial injection, CFA-injected mice displayed robust pain-related behaviors (which included flinching, guarding, impaired limb use, and reduced weight bearing), whereas animals injected with vehicle alone displayed no significant pain-related behaviors. Similarly, in the CFA-injected knee joint, but not in the vehicle-injected knee joint, a remarkable increase was noted in the number of CD68+ macrophages, density of PECAM+ blood vessels, and density and formation of neuroma-like structures by CGRP+, NF200+, and TH+ nerve fibers in the synovium and periosteum.CONCLUSIONS:Sensory and sympathetic nerve fibers that innervate the aged knee joint clearly maintain the capacity for robust nerve sprouting and formation of neuroma-like structures after inflammation/injury. Understanding the factors that drive this neuroplasticity, whether this pathologic reorganization of nerve fibers contributes to chronic joint pain, and how the phenotype of sensory and sympathetic nerves changes with age may provide pharmacologic insight and targets for better controlling aging-related joint pain.
EISSN:
1478-6362
DOI:
10.1186/ar3826
Version:
Final published version
Additional Links:
http://arthritis-research.com/content/14/3/R101

Full metadata record

DC FieldValue Language
dc.contributor.authorJimenez-Andrade, Juanen
dc.contributor.authorMantyh, Patricken
dc.date.accessioned2016-05-20T09:05:48Z-
dc.date.available2016-05-20T09:05:48Z-
dc.date.issued2012en
dc.identifier.citationJimenez-Andrade and Mantyh Arthritis Research & Therapy 2012, 14:R101 http://arthritis-research.com/content/14/3/R101en
dc.identifier.doi10.1186/ar3826en
dc.identifier.urihttp://hdl.handle.net/10150/610392-
dc.description.abstractINTRODUCTION:Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic nerve sproutingen
dc.description.abstracthowever, neuroplasticity is generally thought to be greater in young versus old nerves. Here we explore whether sensory and sympathetic nerve fibers can undergo a significant ectopic nerve remodeling in the painful arthritic knee joint of geriatric mice.METHODS:Vehicle (saline) or complete Freund's adjuvant (CFA) was injected into the knee joint of 27- to 29-month-old female mice. Pain behaviors, macrophage infiltration, neovascularization, and the sprouting of sensory and sympathetic nerve fibers were then assessed 28 days later, when significant knee-joint pain was present. Knee joints were processed for immunohistochemistry by using antibodies raised against CD68 (monocytes/macrophages), PECAM (endothelial cells), calcitonin gene-related peptide (CGRPen
dc.description.abstractsensory nerve fibers), neurofilament 200 kDa (NF200en
dc.description.abstractsensory nerve fibers), tyrosine hydroxylase (THen
dc.description.abstractsympathetic nerve fibers), and growth-associated protein 43 (GAP43en
dc.description.abstractnerve fibers undergoing sprouting).RESULTS:At 4 weeks after initial injection, CFA-injected mice displayed robust pain-related behaviors (which included flinching, guarding, impaired limb use, and reduced weight bearing), whereas animals injected with vehicle alone displayed no significant pain-related behaviors. Similarly, in the CFA-injected knee joint, but not in the vehicle-injected knee joint, a remarkable increase was noted in the number of CD68+ macrophages, density of PECAM+ blood vessels, and density and formation of neuroma-like structures by CGRP+, NF200+, and TH+ nerve fibers in the synovium and periosteum.CONCLUSIONS:Sensory and sympathetic nerve fibers that innervate the aged knee joint clearly maintain the capacity for robust nerve sprouting and formation of neuroma-like structures after inflammation/injury. Understanding the factors that drive this neuroplasticity, whether this pathologic reorganization of nerve fibers contributes to chronic joint pain, and how the phenotype of sensory and sympathetic nerves changes with age may provide pharmacologic insight and targets for better controlling aging-related joint pain.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://arthritis-research.com/content/14/3/R101en
dc.rights© 2012 Mantyh et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleSensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric miceen
dc.typeArticleen
dc.identifier.eissn1478-6362en
dc.contributor.departmentDepartment of Pharmacology, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USAen
dc.contributor.departmentUnidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Calle 16 y Lago de Reynosa, Reynosa, 88740, Méxicoen
dc.contributor.departmentArizona Cancer Center, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USAen
dc.contributor.departmentResearch Service, VA Medical Center, One Veterans Drive, Minneapolis, MN 55417, USAen
dc.identifier.journalArthritis Research & Therapyen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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