Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve.
Chronic constriction of the sciatic nerve, leading to a hyperalgesic state, results in a partial lesion wherein some axons are injured and others remain intact. Here we sought to characterize reactive changes which occur in DRG cell bodies of injured and uninjured axons projecting to skin and muscle. Using immunohistochemistry combined with flurorogold and fluororuby retrograde labelling to define DRG cell bodies associated with injured and uninjured axons, we analysed the DRG immunoreactivity (IR) for tumour necrosis factor-alpha (TNF), interleukin-10 (IL-10), the sensory neuron-specific channel vanilloid receptor 1 (VR1), isolectin B4 (IB4) and calcitonin-gene-related peptide (CGRP) 4 days after a unilateral chronic constriction injury (CCI) of the rat sciatic nerve. TNF IR was predominantly localized in neuronal DRG cells. In DRG with an intact nerve, TNF IR was present in 45%, IL-10 IR in 46%, VR1 IR in 44%, IB4 IR in 51% and CGRP IR in 40% of all neuronal profiles. Four days after CCI, TNF IR was increased in medium-sized neurons, whereas IR for IL-10, VR1 and IB4, predominantly present in small neurons, was reduced. Importantly, not only injured but also adjacent spared neurons contributed markedly to increased TNF IR. Neurons projecting to both muscle and skin displayed upregulated TNF IR after CCI. TNF in medium-sized neurons colocalized with neurofilament and trkB, but not with IB4, trkA or RET, suggesting a selective phenotypic switch in presumably low-threshold myelinated primary afferents. Spared myelinated fibres with intact sensory functions but upregulated TNF expression may contribute to behavioural changes observed after nerve injury.
Schäfers
Maria
M
Department of Neurology, University of Würzburg, Josef-Schneider-Str 11, 97080 Würzburg, Germany. mschaeers@ucsd.edu
Geis
Christian
C
Svensson
Camilla I
CI
Luo
Z David
ZD
Sommer
Claudia
C
D000818:Animals; D001370:Axonal Transport; D015153:Blotting, Western / Q000379:methods; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D048429:Cell Size; D029721:Drosophila Proteins / Q000378:metabolism; D053331:Ectodysplasins; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006023:Glycoproteins; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016753:Interleukin-10 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000294:innervation; D009409:Nerve Crush / Q000379:methods; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology; D012867:Skin / Q000294:innervation; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D029721:Drosophila Proteins; C506018:EDA protein, human; D053331:Ectodysplasins; C506019:Eda protein, mouse; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D037102:Lectins; D008565:Membrane Proteins; D016900:Neurofilament Proteins; D011955:Receptors, Drug; D014409:Tumor Necrosis Factor-alpha; C482860:UCHL1 protein, human; C473590:isolectin B4-binding glycoprotein, mouse; C051774:neurofilament protein H; D016753:Interleukin-10; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020813:Receptor, trkB; C416649:Ret protein, Drosophila; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide