Skin inflammatory cytokine gene expression in chronic whiplash-associated disorder: a cross-sectional study

Neurological findings are present in some patients with whiplash-associated disorder (WAD) Grade II, including reduced intra-epidermal nerve fibre density (IENFD). Reasons for reduced IENFD in WAD are unclear. This exploratory study assessed (i) skin inflammatory cytokine expression in people with chronic WAD II, and (ii) associations between skin inflammatory cytokine gene expression, IENFD, and clinical factors. Skin mRNA expression of genes encoding inflammatory cytokines at the finger and ankle in chronic WAD II (N = 21) was compared with age- and sex-matched controls (N = 21). Realtime quantitative polymerase chain reaction analysis (RT-qPCR) was performed blinded to study group. Genes examined encoded tumour necrosis factor (TNF), interleukin (IL)-6, IL-8, IL-1β and IL-10, expressed relative to a house-keeping control gene (HPRT1). Clinical outcomes were pain, disability, and psychological measures. Gene expression was compared between groups using Wilcoxon rank-sum tests and associations between gene expression, IENFD and clinical outcomes evaluated using Spearman correlations. Benjamini–Hochberg correction was performed (5% FDR). At the finger, TNF mRNA expression was ~ twofold higher in chronic WAD than controls (median [IQR] TNF/HPRT1: 3.47 [4.16] vs 1.80 [2.33], P = 0.006). There were no group differences in expression of genes encoding other cytokines, nor group differences at the ankle. No significant correlations were found between gene expression and IENFD, pain, disability and psychological measures at the finger or ankle. These novel findings suggest an association between local skin inflammatory processes and chronic WAD at the finger, however specific links between skin cytokine expression, reduced IENFD or clinical outcomes remain unclear.