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Identification of Novel Biomarkers of Neuropathic Pain: A Translational Study from Rat to Human

Young, Bethan C (2020) Identification of Novel Biomarkers of Neuropathic Pain: A Translational Study from Rat to Human. Doctoral thesis, University of Huddersfield.

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Abstract

Neuropathic pain is a common chronic condition which remains poorly understood. Twenty
percent of patients receiving treatment continue to experience moderate to severe pain, due to
limited diagnostic and symptom management programmes. The development of objective
diagnostic strategies and more effective medications requires identification of robust
biomarkers of neuropathic pain. To this end, several potential biomarkers of chronic
neuropathic pain were identified by assessing gene expression profiles of an animal model of
neuropathic pain, and differential gene expression in patients to determine the potential
translational mechanisms of neuropathic pain in an animal model to a clinical cohort.

Dorsal horn tissue extracted from a Sprague Dawley rat spinal nerve ligation model (35 days
post-surgery, n=8) and sham operated controls (n=8) was used for Affymetrix Rat Transcriptome
Array 1.0 to identify differentially expressed genes. Genes with significant expression changes
(p<0.05, fold change ±1.25) were also measured by qPCR in clinical neuropathic pain blood
samples (n=53) and non- neuropathic pain control samples (n=65).

The gene expression analysis revealed a subset of significant differentially regulated genes
involved in inflammatory processes and apoptosis. This demonstrated cross-species validation
of eight genes by assessing their expression in blood samples from neuropathic pain patients.
These include A3GALT2, CASP1, CASP4, CASP5, CCR5, FPR2, SH3BGRL3, and TMEM88. Molecules
which demonstrate an active role in human neuropathic pain have the potential to be developed
into a biological measure for objective diagnostic tests, or as novel drug targets for improved
pain management. Such developments could help to relieve the social and economic burden of
neuropathic pain by restoring patient health-related quality of life.

Item Type: Thesis (Doctoral)
Subjects: Q Science > QR Microbiology
Schools: School of Applied Sciences
Depositing User: Jan Appleyard
Date Deposited: 03 Mar 2021 15:22
Last Modified: 03 Mar 2021 15:22
URI: http://eprints.hud.ac.uk/id/eprint/35431

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