The Development of Translational Biomarkers as a Tool for Improving the Understanding, Diagnosis and Treatment of Chronic Neuropathic Pain

David A. Buckley, Elaine M. Jennings, Nikita N. Burke, Michelle Roche, Veronica McInerney, Jonathan D. Wren, David P. Finn, Patrick C. McHugh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Chronic neuropathic pain (CNP) is one of the most significant unmet clinical needs in modern medicine. Alongside the lack of effective treatments, there is a great deficit in the availability of objective diagnostic methods to reliably facilitate an accurate diagnosis. We therefore aimed to determine the feasibility of a simple diagnostic test by analysing differentially expressed genes in the blood of patients diagnosed with CNP of the lower back and compared to healthy human controls. Refinement of microarray expression data was performed using correlation analysis with 3900 human 2-colour microarray experiments. Selected genes were analysed in the dorsal horn of Sprague–Dawley rats after L5 spinal nerve ligation (SNL), using qRT-PCR and ddPCR, to determine possible associations with pathophysiological mechanisms underpinning CNP and whether they represent translational biomarkers of CNP. We found that of the 15 potential biomarkers identified, tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression was upregulated in chronic neuropathic lower back pain (CNBP) (p = 0.0049) which positively correlated (R = 0.68, p = ≤0.05) with increased plasma TIMP1 levels in this group (p = 0.0433). Moreover, plasma TIMP1 was also significantly upregulated in CNBP than chronic inflammatory lower back pain (p = 0.0272). In the SNL model, upregulation of the Timp1 gene was also observed (p = 0.0058) alongside a strong trend for the upregulation of melanocortin 1 receptor (p = 0.0847). Our data therefore highlights several genes that warrant further investigation, and of these, TIMP1 shows the greatest potential as an accessible and translational CNP biomarker.

LanguageEnglish
Pages2420-2430
Number of pages11
JournalMolecular Neurobiology
Volume55
Issue number3
Early online date30 Mar 2017
DOIs
Publication statusPublished - 1 Mar 2018

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Neuralgia
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1
Chronic Pain
Biomarkers
Low Back Pain
Spinal Nerves
Genes
Ligation
Up-Regulation
Receptor, Melanocortin, Type 1
Therapeutics
Modern 1601-history
Routine Diagnostic Tests
Sprague Dawley Rats
Color
Gene Expression
Polymerase Chain Reaction

Cite this

Buckley, David A. ; Jennings, Elaine M. ; Burke, Nikita N. ; Roche, Michelle ; McInerney, Veronica ; Wren, Jonathan D. ; Finn, David P. ; McHugh, Patrick C. / The Development of Translational Biomarkers as a Tool for Improving the Understanding, Diagnosis and Treatment of Chronic Neuropathic Pain. In: Molecular Neurobiology. 2018 ; Vol. 55, No. 3. pp. 2420-2430.
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The Development of Translational Biomarkers as a Tool for Improving the Understanding, Diagnosis and Treatment of Chronic Neuropathic Pain. / Buckley, David A.; Jennings, Elaine M.; Burke, Nikita N.; Roche, Michelle; McInerney, Veronica; Wren, Jonathan D.; Finn, David P.; McHugh, Patrick C.

In: Molecular Neurobiology, Vol. 55, No. 3, 01.03.2018, p. 2420-2430.

Research output: Contribution to journalArticle

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