Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls: a hypothesis-generating pilot study
2015 (English)In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 8, 321-333 p.Article in journal (Refereed) Published
Pain medicine lacks objective biomarkers to guide diagnosis and treatment. Combining two-dimensional gel proteomics with multivariate data analysis by projection, we exploratively analyzed the cerebrospinal fluid of eleven patients with severe peripheral neuropathic pain due to trauma and/or surgery refractory to conventional treatment and eleven healthy controls. Using orthogonal partial least squares discriminant analysis, we identified a panel of 36 proteins highly discriminating between the two groups. Due to a possible confounding effect of age, a new model with age as outcome variable was computed for patients (n=11), and four out of 36 protein spots were excluded due to a probable influence of age. Of the 32 remaining proteins, the following seven had the highest discriminatory power between the two groups: an isoform of angiotensinogen (upregulated in patients), two isoforms of alpha-1-antitrypsin (downregulated in patients), three isoforms of haptoglobin (upregulated in patients), and one isoform of pigment epithelium-derived factor (downregulated in patients). It has recently been hypothesized that the renin–angiotensin system may play a role in the pathophysiology of neuropathic pain, and a clinical trial of an angiotensin II receptor antagonist was recently published. It is noteworthy that when searching for neuropathic pain biomarkers with a purely explorative methodology, it was indeed a renin–angiotensin system protein that had the highest discriminatory power between patients and controls in the present study. The results from this hypothesis-generating pilot study have to be confirmed in larger, hypothesis-driven studies with age-matched controls, but the present study illustrates the fruitfulness of combining proteomics with multivariate data analysis in hypothesis-generating pain biomarker studies in humans.
Place, publisher, year, edition, pages
Dovepress , 2015. Vol. 8, 321-333 p.
Cerebrospinal fluid, multivariate data analysis, neuropathic pain, proteomics
IdentifiersURN: urn:nbn:se:liu:diva-121493DOI: 10.2147/JPR.S82970ISI: 000364718500002PubMedID: 26170714OAI: oai:DiVA.org:liu-121493DiVA: diva2:855848
Funding agencies: Swedish Research Council; Swedish Council for Working Life and Social Research [2010-0913]; County Council of Ostergotland (Sinnescentrum); Halsofonden foundation2015-09-222015-09-222016-04-25Bibliographically approved