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In this study, we recruited 50 chronic pain (neuropathic and nociceptive) and 43 pain-free controls to identify specific blood biomarkers of chronic neuropathic pain (CNP). Affymetrix microarray was carried out on a subset of samples selected 10 CNP and 10 pain-free control participants. The most significant genes were cross-validated using the entire dataset by quantitative real-time PCR (qRT-PCR). In comparative analysis of controls and CNP patients,  WLS  ( P  = 4.80 × 10 –7 ),  CHPT1  ( P  = 7.74 × 10 –7 ) and  CASP5  ( P  = 2.30 × 10 –5 ) were highly significant, whilst  FGFBP2  ( P  = 0.00162),  STAT1  ( P  = 0.00223),  FCRL6  ( P  = 0.00335),  MYC  ( P  = 0.00335),  XCL2  ( P  = 0.0144) and  GZMA  ( P  = 0.0168) were significant in all CNP patients. A three-arm comparative analysis was also carried out with control as the reference group and CNP samples differentiated into two groups of high and low S-LANSS score using a cut-off of 12.  STAT1 ,  XCL2  and  GZMA  were not significant but  KIR3DL2  ( P  = 0.00838),  SH2D1B  ( P  = 0.00295) and  CXCR31  ( P  = 0.0136) were significant in CNP high S-LANSS group (S-LANSS score &gt; 12), along with  WLS (P  = 8.40 × 10 –5 ),  CHPT1  ( P  = 7.89 × 10 –4 ) , CASP5  ( P  = 0.00393) , FGFBP2  ( P  = 8.70 × 10 –4 ) and  FCRL6  ( P  = 0.00199), suggesting involvement of immune pathways in CNP mechanisms. None of the genes was significant in CNP samples with low (&lt; 12) S-LANSS score. The area under the receiver operating characteristic (AUROC) analysis showed that combination of  MYC ,  STAT1 ,  TLR4 ,  CASP5  and  WLS  gene expression could be potentially used as a biomarker signature of CNP (AUROC − 0.852, (0.773, 0.931 95% CI)).

The Identification of Blood Biomarkers of Chronic Neuropathic Pain by Comparative Transcriptomics