title: Experimental arthritis causes tumor necrosis factor-alpha-dependent infiltration of macrophages into rat dorsal root ganglia which correlates with pain-related behavior.
abstract: After peripheral nerve damage macrophages infiltrate the dorsal root ganglia (DRG) in which cell bodies of lesioned neurons are located. However, infiltration of macrophages into the DRGs was also reported in complete Freund's adjuvant (CFA)-induced inflammation raising the question whether CFA inflammation induces nerve cell damage or whether peripheral inflammation may also trigger macrophage infiltration into DRGs. Related questions are, first, which signals trigger macrophage infiltration into DRGs and, second, is macrophage infiltration correlated with pain-related behavior. Using the rat model of unilateral antigen-induced arthritis (AIA) in the knee we found a massive infiltration of ED1(+) macrophages into the ipsi- and contralateral lumbar DRGs but not into thoracic DRGs. At no time point of AIA DRG neurons showed expression of activating transcription factor-3 (ATF3) indicating that macrophage infiltration is not explainable by nerve cell lesions in this model. During AIA, lumbar but not thoracic DRGs exhibited a bilateral de novo expression of vascular cell adhesion molecule-1 (VCAM-1) which is known to be involved in macrophage infiltration. Tumor necrosis factor-alpha (TNF-alpha) neutralization with etanercept or infliximab treatment after induction of AIA significantly reduced both macrophage infiltration and VCAM-1 expression. It also decreased mechanical hyperalgesia at the inflamed joint although the joint inflammation itself was barely attenuated, and it reduced mechanical hyperalgesia at the non-inflamed contralateral knee joint. Thus, bilateral segment-specific infiltration of macrophages into DRGs is part of an unilateral inflammatory process in peripheral tissue and it may be involved in the generation of hyperalgesia in particular on the non-inflamed side.
authors: Institute of Physiology I, University Hospital Jena, Germany. Gisela.SegondvonBanchet@mti.uni-jena.de
authors: Gisela
authors: G
authors: Segond von Banchet
authors: Michael K
authors: MK
authors: Boettger
authors: Nadja
authors: N
authors: Fischer
authors: Mieczyslaw
authors: M
authors: Gajda
authors: Rolf
authors: R
authors: Bräuer
authors: Hans-Georg
authors: HG
authors: Schaible
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D053331:Ectodysplasins / Q000378:metabolism; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006930:Hyperalgesia / Q000209:etiology*; D007718:Knee Injuries / Q000209:etiology; D008264:Macrophages / Q000473:pathology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; D000906:Antibodies; C497108:Atf3 protein, rat; D053331:Ectodysplasins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D005620:Freund's Adjuvant