Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve

Authors

  • Maria Schäfers,

    1. Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany
    2. Anaesthesiology Research Laboratory, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0818, USA
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  • Christian Geis,

    1. Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany
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  • Camilla I. Svensson,

    1. Anaesthesiology Research Laboratory, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0818, USA
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  • Z. David Luo,

    1. Anaesthesiology Research Laboratory, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0818, USA
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  • Claudia Sommer

    1. Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany
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: Dr Maria Schäfers, 2Anaesthesiology Research Laboratory, as above.
E-mail: mschaefers@ucsd.edu

Abstract

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.

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