Serum C-reactive protein levels predict regional brain responses to noxious cold stimulation of the hand in chronic whiplash associated disorders

Abstract

Abstract Background and aims Whiplash Associated Disorders (WAD) are a costly health burden. The condition is characterised by sensory disturbances such as widespread hyperalgesia likely indicative of central hyperexcitability. Recently elevated levels of pro-inflammatory biomarkers have also found in acute and chronic WAD. The aim of this cross-sectional study was to investigate the relationship between inflammatory biomarkers and pain processing in people with persistent whiplash associated disorders (WAD). Methods Twenty one participants with chronic whiplash (>3 months) were recruited. Venous blood samples were collected and assays performed for C-reactive protein (CRP) and TNF-α. Blood oxygen level-dependent (BOLD) contrast images of the brain were acquired with a Siemens 1.5T MRI scanner during repeated 24 s stimulus blocks of innocuous or painful stimuli (thumbnail pressure and cold stimulation of dorsum of hand) separated by 36 s inter-stimulus intervals. Stimulus intensities used during scanning were at the level of participants’ thresholds for moderate pain. Parameter estimates representing BOLD signal increases during painful events from each participant were tested for associations with inflammatory biomarkers. Results Clinically relevant levels of CRP and TNF-α were found in 33% and 38% of participants. Levels of CRP showed a positive correlation with levels of cold pain activation in brain regions including the anterior insula, posterior parietal cortex, caudate and thalamus (p corrected < 0.05). Levels of TNF-α were not related to activation levels during either noxious pressure or cold. Pressure pain activations also did not show a relationship with CRP levels. Conclusions Shared variance between inflammation and increased levels of regional pain-related activation in people with persistent whiplash symptoms is apparent for cold, but not pressure stimuli. Implications The results highlight cold pain processing as an important aspect of whiplash chronicity, although the implications of this modality-specific effect are not readily apparent.