Multivariate proteomic analysis of the cerebrospinal fluid of patients with peripheral neuropathic pain and healthy controls - a hypothesis-generating pilot study

被引:49
作者
Backryd, Emmanuel [1 ,2 ]
Ghafouri, Bijar [1 ,2 ]
Carlsson, Anders K. [1 ,2 ]
Olausson, Patrik [1 ,2 ]
Gerdle, Bjorn [1 ,2 ]
机构
[1] Linkoping Univ, Fac Hlth Sci, Div Community Med, Dept Med & Hlth Sci, SE-58185 Linkoping, Sweden
[2] Anaesthet Operat & Specialty Surg Ctr, Pain & Rehabil Ctr, Linkoping, Sweden
基金
瑞典研究理事会;
关键词
cerebrospinal fluid; multivariate data analysis; neuropathic pain; proteomics; 2-DIMENSIONAL GEL-ELECTROPHORESIS; SPINAL-CORD STIMULATION; ANGIOTENSIN-II; BIOMARKER DISCOVERY; APOLIPOPROTEIN-E; CYSTATIN-C; PROTEINS; HAPTOGLOBIN; SYSTEMS; ALPHA-1-ANTITRYPSIN;
D O I
10.2147/JPR.S82970
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:321 / 333
页数:13
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