Volume 13, Issue 4 pp. 387-398

Comparison of dorsal root ganglion gene expression in rat models of traumatic and HIV-associated neuropathic pain

Klio Maratou

Klio Maratou

Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London SW10 9NH, UK

Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Du Cane Road, W12 0NN, UK

London Pain Consortium.

These authors contributed equally to the study.

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Victoria C.J. Wallace

Victoria C.J. Wallace

Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London SW10 9NH, UK

London Pain Consortium.

These authors contributed equally to the study.

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Fauzia S. Hasnie

Fauzia S. Hasnie

Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London SW10 9NH, UK

London Pain Consortium.

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Kenji Okuse

Kenji Okuse

Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, UK

London Pain Consortium.

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Ramine Hosseini

Ramine Hosseini

Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK

London Pain Consortium.

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Nipurna Jina

Nipurna Jina

ICH Gene Microarray Centre, Institute of Child Health, University College London, London WC1N 1EH, UK

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Julie Blackbeard

Julie Blackbeard

Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London SW10 9NH, UK

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Timothy Pheby

Timothy Pheby

Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London SW10 9NH, UK

London Pain Consortium.

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Christine Orengo

Christine Orengo

Biomolecular Structure and Modelling Unit, Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, UK

London Pain Consortium.

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Anthony H. Dickenson

Anthony H. Dickenson

Department of Neuropharmacology, University College London, London WC1E 6BT, UK

London Pain Consortium.

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Stephen B. McMahon

Stephen B. McMahon

Department of Anatomy and Human Sciences, Kings College London, Guy's Hospital Campus, London SE1 1UL, UK

London Pain Consortium.

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Andrew S.C. Rice

Corresponding Author

Andrew S.C. Rice

Pain Research Group, Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital Campus, London SW10 9NH, UK

London Pain Consortium.

Tel.: +44 20 8746 8156; fax: +44 20 8237 5109. [email protected]Search for more papers by this author
First published: 09 January 2012
Citations: 72

These authors contributed equally to the study.

ABSTRACT

To elucidate the mechanisms underlying peripheral neuropathic pain in the context of HIV infection and antiretroviral therapy, we measured gene expression in dorsal root ganglia (DRG) of rats subjected to systemic treatment with the anti-retroviral agent, ddC (Zalcitabine) and concomitant delivery of HIV-gp120 to the rat sciatic nerve. L4 and L5 DRGs were collected at day 14 (time of peak behavioural change) and changes in gene expression were measured using Affymetrix whole genome rat arrays. Conventional analysis of this data set and Gene Set Enrichment Analysis (GSEA) was performed to discover biological processes altered in this model. Transcripts associated with G protein coupled receptor signalling and cell adhesion were enriched in the treated animals, while ribosomal proteins and proteasome pathways were associated with gene down-regulation. To identify genes that are directly relevant to neuropathic mechanical hypersensitivity, as opposed to epiphenomena associated with other aspects of the response to a sciatic nerve lesion, we compared the gp120+ddC-evoked gene expression with that observed in a model of traumatic neuropathic pain (L5 spinal nerve transection), where hypersensitivity to a static mechanical stimulus is also observed. We identified 39 genes/expressed sequence tags that are differentially expressed in the same direction in both models. Most of these have not previously been implicated in mechanical hypersensitivity and may represent novel targets for therapeutic intervention. As an external control, the RNA expression of three genes was examined by RT-PCR, while the protein levels of two were studied using western blot analysis.

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