Human Studies

Spatial integration of parts of the body is impaired in patients with complex regional pain syndrome (CRPS). Since the training of mental rotation (MR) has been shown to be among the effective therapy strategies for CRPS, impairment of MR is also important for the pathophysiological understanding of CRPS. The aim of this study was to evaluate whether differences in neural representation of MR occur between CRPS patients and healthy controls. Therefore we included 15 chronic CRPS patients and 15 age-/gender matched healthy controls. We assessed behavioral (accuracy and reaction time for MR of both hands), clinical (DASH) and MRI (T1, fMRI during MR) data. Reaction times in the patient group were delayed compared to healthy controls without a lateralization effect for affected hand side. Although both groups showed an activation pattern typical for MR, only HC showed a highly significant contrast for the rotated versus unrotated hands in the right intraparietal sulcus. CRPS patients showed a reduction of fMRI activation in areas including subthalamic nucleus, nucleus accumbens and putamen. Regression analysis for the CRPS group emphasized the importance of putamen and n. accumbens activation for MR performance. This study highlights the reduced access of CRPS patients for mental resources modulating arousal, emotional response and subcortical sensorimotor integration. PERSPECTIVE: This study localized the underlying neural responses for impaired mental rotation (MR) in patients with complex regional pain syndrome (CRPS) as a decrease in basal ganglia (putamen) and nucleus accumbens activation.

Although chronic postsurgical pain (CPSP) is a major health care problem, pain-related functional interference has rarely been investigated. Using the PAIN OUT registry, we evaluated patients' pain-related outcomes on the first postoperative day, and their pain-related interference with daily living (Brief Pain Inventory) and neuropathic symptoms (DN4: douleur neuropathique en 4 questions) at 6 months after surgery. Endpoints were pain interference total scores (PITS) and their association with pain and DN4 scores. Furthermore, possible risk factors associated with impaired function at M6 were analyzed by ordinal regression analysis with PITS groups (no to mild, moderate, and severe interference) as a dependent three-stage factor. Odds ratios with 95% confidence intervals were calculated. Of 2322 patients, 15.3% reported CPSP with an average pain score ≥3 (numeric rating scale 0-10). Risk for a higher PITS group increased by 190% (odds ratio [95% confidence interval]: 2.9 [2.7-3.2]; P < 0.001) in patients with CPSP, compared to without CPSP. A positive DN4 independently increased risk by 29% (1.3 [1.12-1.45]; P < 0.001). Preexisting chronic pain (3.6 [2.6-5.1]; P < 0.001), time spent in severe acute pain (2.9 [1.3-6.4]; P = 0.008), neurosurgical back surgery in males (3.6 [1.7-7.6]; P < 0.001), and orthopedic surgery in females (1.7 [1.0-3.0]; P = 0.036) were the variables with strongest association with PITS. Pain interference total scores might provide more precise information about patients' outcomes than pain scores only. Because neuropathic symptoms increase PITS, a suitable instrument for their routine assessment should be defined.

Recent studies have reported structural and functional abnormalities in multiple brain regions of classical trigeminal neuralgia (CTN) patients. Differences in spontaneous neuronal activity between CTN patients and healthy subjects, however, remain unknown. The aim of the present study was to investigate alterations in brain activity by application of amplitude of low frequency fluctuation (ALFF), thus analyzing the correlation between durations of spontaneous pain intensity and ALFF values in CTN patients. A total of 28 CTN patients (male, n=12; female, n=16) and 28 healthy controls (HCs; male, n=12; female, n=16) matched for age and sex were enrolled. All subjects underwent resting‑state functional magnetic resonance imaging and changes in spontaneous brain activity were investigated using an ALFF method. Receiver operating characteristic (ROC) curve analysis was applied to differentiate ALFF values of CTN patients from HCs. Altered ALFF values and clinical manifestations were evaluated using Pearson's correlation analysis. ALFF values of the bilateral inferior cerebellum, bilateral fusiform gyrus, right precentral gyrus, left inferior temporal gyrus, right superior cerebellum, left inferior occipital gyrus and right superior occipital gyrus were significantly higher in CTN patients when compared to HCs. ROC curve analysis of each brain revealed a near‑perfect AUC accuracy. Pearson's correlation analysis revealed the visual analog scale of the right eye to be positively correlated with both left inferior temporal and occipital gyral findings, while episode duration likewise was positively associated with left inferior temporal gyral findings. CTN patients exhibited abnormal spontaneous activity in multiple brain regions closely related to pain regulation and perception, while VAS and CTN episode duration were positively correlated with ALFF signal values in some brain regions. The present findings provide further insight into the pathological mechanisms underlying CTN.

The present study's objective is to understand the causal mechanisms underpinning the recovery of individuals with whiplash-associated disorders (WAD). We applied Bayesian Networks (BN) to answer two study aims: (1) to identify the causal mechanism(s) of recovery underpinning neck-specific exercise, and (2) quantify if the cyclical pathway of the fear avoidance model (FAM) is supported by the present data.