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Background: Whiplash injuries typically occur from a motor vehicle collision and lead to chronic whiplash-associated disorders (CWAD) in 20% to 50% of cases. Changes in neurotransmission, metabolism, and networks seem to play a role in the pathogenic mechanism of CWAD., Objectives: To further elucidate the functional brain alterations, a neurophysiological study was performed to investigate the somatosensory processing of CWAD patients by comparing the event-related potentials (ERPs) resulting from electrical nociceptive stimulation between patients suffering from CWAD and healthy controls (HC)., Study Design: Case-control study., Setting: University Hospital in Ghent., Methods: In this case-control study (CWAD patients/HC: 50/50), ankle and wrist electrical pain thresholds (EPT), and amplitude and latency of the event-related potentials (ERPs) resulting from 20 electrical stimuli were investigated. Correlations between the ERP characteristics, EPT, self-reported pain, disability, pain catastrophizing, and self-reported symptoms of central sensitization were investigated., Results: Only the latency of the P3 component after left wrist stimulation (t = -2.283; P = 0.023) differed between both groups. In CWAD patients, the ankle EPT correlated with the amplitude of the corresponding P1 (rho s = 0.293; P = 0.044) and P3 (rho s = 0.306; P = 0.033), as well as with the amplitude of the P3 to left wrist stimulation (rho s = 0.343; P = 0.017). Self-reported symptoms of CS correlated with right wrist P3 amplitude (rho s = 0.308; P = 0.030) and latency (rho s = -0.341; P = 0.015), and the worst pain reported during the past week was correlated with left wrist P1 latency (rho s = 0.319; P = 0.029)., Limitations: Although the inclusion criteria stated that CWAD patients had to report a moderate-to-severe pain-related disability, 8 of the included CWAD patients (that scored above this threshold in the inclusion questionnaire), scored below the required cutoff at baseline., Conclusions: The CWAD patients did not show signs of hypersensitivity, but their ERP characteristics were related to the intensity of the applied stimulus, self-reported symptoms of CS, and the worst pain reported during the past week.

Background: The biopsychosocial-spiritual model recognizes the impact of religious factors in modulating the experience of pain. Religious beliefs are factors that can influence perceptions, emotions, and behavior, all of which have important implications on health, pain experience, and treatment outcomes., Objectives: The aim of the present study was to identify if and how religious beliefs and attitudes can influence pain intensity, pain interference, pain-related beliefs and cognitions, emotions, and coping among patients with chronic musculoskeletal pain., Study Design: Systematic review., Methods: This systematic review was conducted and reported, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). An electronic search was conducted in 4 online databases (PubMed, Embase, Web of science, and PsychArticles) and complemented with a hand search (PROSPERO registry: CRD42020161289). Two reviewers independently performed eligibility screening, risk of bias assessment, and data extraction. The risk of bias of the included studies was assessed using the Newcastle Ottawa Scale., Results: Nine cross-sectional studies and one case-control study were included in the review. The methodological quality of the included studies ranged from low to high. The results gathered regarding the association between religiosity and pain intensity, disability, or pain interference were found to be conflicting. Limited evidence suggests that religiosity is positively associated with worse pain-related beliefs and cognitions, worse pain-related emotion, and better pain acceptance. There is insufficient data available to support the claim that religiosity is negatively associated with physical functioning and pain-related self-efficacy in people with chronic musculoskeletal pain., Limitations: The number of included studies was small, with a low level of evidence, and a possible risk of bias., Conclusion: This systematic review shows low evidence and conflicting results for the presence of associations between religiosity and different pain domains such as pain intensity, disability, and pain-related cognitions or emotions in people with chronic musculoskeletal pain.

Background: Chronic pain affects 20 to 30% of the adult population worldwide and is consequently the leading cause of disability. Current developments in brain imaging technology are increasing the understanding of the pathophysiology of (chronic) pain and enabling the possibility to objectify pain. As a result, our view of the brain has evolved from a static organ to a dynamic organ that constitutes an adaptable network of linked regions. Graph theory has emerged as a framework to analyze such networks and can be applied to investigate a range of topological properties of both the functional and structural brain network or connectome, thus providing meaningful information about the organization of human brain networks., Objectives: The aim of this systematic review is to determine whether connectivity differs between chronic pain patients and healthy controls by integrating previous studies that performed graph analyses on structural or functional connectivity. A secondary aim was to determine whether graph measures correlate to clinical outcomes., Study Design: Systematic review., Methods: Relevant articles were searched for in PubMed and Web of Science. These were screened against certain criteria and assessed for quality., Results: On a global level the transitivity, betweenness centrality, intramodular degree, and rich club organization differed between chronic pain patients and healthy controls, but the path length, modularity, degree, and (Hub Disruption Index [HDI] of) participation coefficient did not differ between both groups, along with the small-worldness. Conflicting evidence still remains about a number of global graph measures, namely the global efficiency, local efficiency, clustering coefficient, and HDI of degree. Significant correlations were found between several nodal and global graph measures on one hand, and clinical outcomes related to pain, disability, and motor control on the other hand., Limitations: No clear conclusions could be made about the majority of the nodal measures, as they were often based on single studies., Conclusion: Differences between chronic pain patients and healthy controls were mostly observed for the global graph measures. Future research is still needed to validate the obtained findings and to expand this knowledge to the chronic pain populations that were not discussed in the included papers.

Background: Although the association of gray matter morphology alterations and pain-related psychosocial characteristics with pain intensity and chronification in people with chronic spinal pain is evident, research on their mutual interaction is scarce and does not account for possible gender differences. Gender-based differences are, however, of utmost importance to consider when examining pain neurobiology., Objectives: To look for gender differences in the association between magnetic resonance imaging- (MRI) derived brain gray matter morphology and self-reported psychosocial characteristics., Study Design: An explorative, observational study., Setting: University Hospitals Ghent and Brussels, Belgium., Methods: Brain gray matter morphology (using MRI) and self-reported psychosocial characteristics were examined in women and men with nonspecific chronic spinal pain. Statistical analyses were performed in SPSS and R to identify differences between men and women regarding brain gray matter, self-reported psychosocial characteristics, as well as gender differences in the association between those outcome measures., Results: A total of 94 people with chronic spinal pain were studied, including 32 men (15 suffering from neck pain, 17 suffering from low back pain; demographics [mean ± SD] age: 45.00 ± 12.02 years; pain duration: 128.37 ± 110.45 months), and 62 women (36 suffering from neck pain, 26 suffering from low back pain; demographics [mean ± SD] age: 38.78 ± 12.69 years; pain duration: 114.27 ± 92.45 months). Woman showed larger (positive) associations of several central brain areas (paracentral, precentral, postcentral, etc.) with perceived consequences (P < 0.001), emotional representations (P < 0.001), chronicity (P < 0.001), and pain catastrophizing (P< 0.001). Men showed larger (both positive and negative) associations of the precuneus cortex, the precentral gyrus, and the insula with perceived personal control (P < 0.001) and kinesiophobia (P < 0.001)., Limitations: Other factors, such as menstrual cycle and medication can have a certain influence, and were only partly taken into consideration in the present investigation to obtain sufficient power. Another limitation is the observational study design, which hampers the possibility to look for causal or temporal interactions., Conclusions: Gray matter morphology relates differently to psychosocial characteristics in women and men. These explorative findings provide ideas for further research to investigate if targeting perceived negative consequences of the illness, perceived emotional representations, perceived chronicity, and pain catastrophizing in women, and perceived personal control of the illness and kinesiophobia in men, could contribute to the normalization of brain alterations in people with nonspecific chronic spinal pain., Key Words: Gray matter, brain morphology, central nervous system, illness perceptions, central sensitization.

Background: Chronic pain has been considered as a biopsychosocial condition in which cognitive and emotional factors as well as biological factors significantly affect perception of pain. Race, ethnicity and culture have a crucial impact on illness beliefs, health care preferences, help-seeking behaviors, and acceptance of medical interventions., Objectives: The aim of the present study was to systematically review the current evidence regarding the racial, ethnic and cultural alterations and differences in pain beliefs, cognitions, and behaviors in patients with chronic musculoskeletal pain (MSKP)., Study Design: Systematic review., Methods: This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses guidelines (PRISMA). PubMed and Web of Science were searched. A first screening was conducted based on title and abstract of the articles. In the second screening, full-texts of the remaining articles were evaluated for the fulfilment of the inclusion criteria. The risk of bias was assessed with the modified Newcastle-Ottawa Scale., Results: A total of 11 articles were included. The methodological quality of the included studies ranged from low to moderate. There is moderate evidence that African-Americans use more praying, hoping, and emotion-focused coping strategies than Caucasians. There is also preliminary evidence regarding the differences in some coping strategies such as distraction, catastrophizing, and problem-focused solving between African-Americans and Caucasians. Preliminary evidence exists regarding the differences in pain coping strategies between the US and Portugal; the US and Singapore; and among 4 French-speaking countries. It is found that Spanish patients with fibromyalgia (FM) have more negative illness perceptions than Dutch patients. There is preliminary evidence that Caucasians have higher self-efficacy than African-Americans. There is also preliminary evidence that New Zealanders have more internal health expectancies than patients from the US. Preliminary evidence is demonstrated that Caucasians with rheumatoid arthritis (RA) have more positive control beliefs than African-Americans. Lastly, there is preliminary evidence that patients from the US believe that they are more disabled, while Singaporeans interpret the pain more by a traditional biomedical perspective., Limitations: Only 11 articles were included. The small number of articles, wide range of assessment methods, and substantial risk of bias in the included studies led the investigator to draw conclusions cautiously., Conclusion: Preliminary to moderate evidence shows the differences in coping strategies, illness perceptions, self-efficacy, fear avoidance beliefs, locus of control, and pain attitudes in different populations. Further prospective and longitudinal studies using standard definitions for race, ethnicity or culture and valid questionnaires for each population are warranted to explore the racial, ethnic and cultural discrepancies in pain beliefs, cognitions, and behaviours., Key Words: Chronic pain, musculoskeletal pain, pain beliefs, pain cognitions, pain behaviors, race, ethnicity, culture.

Background: Patients with chronic whiplash-associated disorders (CWAD) are characterized by pain of traumatic origin, cognitive deficits, and central sensitization (CS). Previous neuroimaging studies revealed altered grey matter volume (GMV) in mild traumatic brain injury patients and chronic pain conditions also characterized by CS. It can therefore be hypothesized that GMV alterations also play a role in the persistent complaints of CWAD. However, brain alterations remain poorly investigated in these patients., Objectives: This study examined regional GMV alterations in patients with CWAD compared to patients with non-traumatic chronic idiopathic neck pain (CINP), who normally do not show CS at a group level, and healthy controls. Additionally, in both patient groups, relationships between regional GMV and measures of cognition as well as pain processing were assessed., Study Design: A cross-sectional case-control study., Setting: This study was performed at the Department of Rehabilitation Sciences and Physiotherapy of Ghent University in cooperation with the Ghent Institute for Functional and Metabolic Imaging., Methods: Ninety-three women (28 healthy controls, 34 CINP patients, and 31 CWAD patients) were enrolled. First, T1-weighted magnetic resonance images (MRIs) were acquired to examine GMV alterations in the brain regions involved in processing cognition and pain. Next, cognitive performance, pain cognitions, and CS symptoms were assessed. Finally, hyperalgesia and conditioned pain modulation efficacy were examined., Results: Regional GMV of the right lateral orbitofrontal cortex, left supramarginal cortex, and left posterior cingulate cortex was decreased in CWAD patients compared to healthy controls (P = 0.023; P = 0.012; P = 0.047, respectively). Additionally, GMV of the right superior parietal cortex and left posterior cingulate cortex was decreased in CWAD patients compared to CINP patients (P = 0.008; P = 0.035, respectively). Decreased regional GMV correlated with worse cognitive performance, higher maladapted pain cognitions, CS symptoms, and hyperalgesia in CWAD patients (rs = -0.515 to -0.657; P < 0.01). In CINP patients, decreased regional GMV correlated only with worse cognitive performance (rs = -0.499 to -0.619; P < 0.01), and no GMV differences compared with the controls could be revealed., Limitations: No conclusions about the causality of the observed relationships can be drawn., Conclusions: These results provide the first evidence for reduced GMV in cortical regions involved in processing cognition and pain in patients with CWAD. Accordingly, it is recommended that therapy approaches for CWAD patients should address the brain and take into account neuroplasticity of the central nervous system (CNS)., Key Words: Whiplash injuries, neck pain, magnetic resonance imaging, grey matter, cognitive dysfunction, pain catastrophizing, central sensitization.

Background: Chronic neck pain affects 50% - 85% of people who have experienced an acute episode. This transition and the persistence of chronic complaints are believed to be mediated by brain alterations among different central mechanisms., Objectives: This study aimed to systematically review and critically appraise the current existing evidence regarding structural and functional brain alterations in patients with whiplash associated disorders (WAD) and idiopathic neck pain (INP). Additionally, associations between brain alterations and clinical symptoms reported in neck pain patients were evaluated., Study Design: Systematic review., Methods: The present systematic review was performed according to the PRISMA guidelines. PubMed, Web of Science, and Cochrane databases were searched. First, the obtained articles were screened based on title and abstract. Secondly, the screening was based on the full text. Risk of bias in included studies was investigated., Results: Twelve studies met the inclusion criteria. Alterations in brain morphology and function, including perfusion, neurotransmission, and blood oxygenation level dependent-signal, were demonstrated in chronic neck pain patients. There is some to moderate evidence for both structural and functional brain alterations in patients with chronic neck pain. In contrast, no evidence for structural brain alterations in acute neck pain patients was found., Limitations: Only 12 articles were included, which allows only cautious conclusions to be drawn., Conclusion: Brain alterations were observed in both patients with chronic WAD and chronic INP. Furthermore, more evidence exists for brain alterations in chronic WAD, and different underlying mechanisms might be present in both pathologies. In addition, pain and disability were correlated with the observed brain alterations. Accordingly, morphological and functional brain alterations should be further investigated in patients with chronic WAD and chronic INP with newer and more sensitive techniques, and associative clinical measurements seem indispensable in future research.

Background: Chronic musculoskeletal pain is characterized by maladaptive central neuroplastic changes. Many observational studies have demonstrated that chronic pain states are associated with brain alterations regarding structure and/or function. Rehabilitation of patients with chronic musculoskeletal pain may include cognitive, exercise, or multimodal therapies., Objective: The current review aims to provide a constructive overview of the existing literature reporting neural correlates, based on brain magnetic resonance imaging (MRI) techniques, following conservative treatment in chronic musculoskeletal pain patients., Study Design: Systematic review of the literature., Setting: University medical centers in Belgium., Methods: The current review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Literature was searched from 3 databases and screened for eligibility. Methodological quality across studies was assessed with Cochrane Collaboration's tool for assessing risk of bias and quality of evidence was determined applying the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach., Results: A total of 9 eligible studies were identified with a predominant high risk of bias. Cognitive behavioral therapy induced several structural and functional changes predominantly in prefrontal cortical regions and a shift from affective to sensory-discriminative brain activity after behavioral extinction training. Multidisciplinary treatment in pediatric complex regional pain syndrome facilitated normalization of functional connectivity of resting-state networks and the amygdala, and increased gray matter in prefrontal and specific subcortical areas. Exercise therapy led to specific for resting-state functional connectivity and a trend towards pressure-induced brain activity changes., Limitations: A very small number of studies was available, which furthermore exhibited small study samples. Moreover, only 2 of the included studies were randomized controlled trials., Conclusions: It is likely that conservative treatments may induce mainly functional and structural brain changes in prefrontal regions in patients with chronic musculoskeletal pain. Due to the relatively high risk of bias across the included studies, future studies with randomized designs are needed to confirm the current findings. In addition, more research evaluating the treatment-induced effects on white matter and whole-brain network dynamics are warranted.Key words: Chronic pain, musculoskeletal pain, MRI, functional MRI, therapy, rehabilitation, cognitive behavioral therapy, exercise therapy.

Background: Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM., Objectives: The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals., Study Design: A randomized crossover design was employed., Setting: The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp., Methods: Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched., Results: A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001)., Limitations: The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long-term relaxation therapies., Conclusions: A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with FM, while cognitive stress and relaxation did not worsen bottom-up sensitization in chronic WAD patients and healthy persons. However, endogenous pain inhibition, assessed using a CPM paradigm, worsened in chronic WAD and FM patients, as well as in healthy people following both interventions.

Background: Chronic neck pain is a common problem with a poorly understood pathophysiology. Often no underlying structural pathology can be found and radiological imaging findings are more related to age than to a patient's symptoms. Besides its common occurrence, chronic idiopathic neck pain is also very disabling with almost 50% of all neck pain patients showing moderate disability at long-term follow-up. Central sensitization (CS) is defined as "an amplification of neural signaling within the central nervous system that elicits pain hypersensitivity," "increased responsiveness of nociceptive neurons in the central nervous system to their normal or subthreshold afferent input," or "an augmentation of responsiveness of central neurons to input from unimodal and polymodal receptors." There is increasing evidence for involvement of CS in many chronic pain conditions. Within the area of chronic idiopathic neck pain, there is consistent evidence for the presence and clinical importance of CS in patients with traumatic neck pain, or whiplash-associated disorders. However, the majority of chronic idiopathic neck pain patients are unrelated to a traumatic injury, and hence are termed chronic idiopathic non-traumatic neck pain. When comparing whiplash with idiopathic non-traumatic neck pain, indications for different underlying mechanisms are found., Objective: The goal of this article was to review the existing scientific literature on the role of CS in patients with chronic idiopathic non-traumatic neck pain., Study Design: Systematic review., Setting: All selected studies were case control studies., Methods: A systematic search of existing, relevant literature was performed via the electronic databases Medline, Embase, Web of Science, Cinahl, PubMed, and Google Scholar. All titles and abstracts were checked to identify relevant articles. An article was considered eligible if it met following inclusion criteria: (1) participants had to be human adults (> 18 years) diagnosed with idiopathic non-traumatic chronic (present for at least 3 months) neck pain; (2) papers had to report outcomes related to CS; and (3) articles had to be full-text reports or original research (no abstracts, case-reports, reviews, meta-analysis, letters, or editorials)., Results: Six articles were found eligible after screening the title, abstract and - when necessary - the full text for in- and exclusion criteria. All selected studies were case-control studies. Overall, results regarding the presence of CS were divergent. While the majority of patients with chronic traumatic neck pain (i.e. whiplash) are characterized by CS, this is not the case for patients with chronic idiopathic neck pain. The available evidence suggests that CS is not a major feature of chronic idiopathic neck pain. Individual cases might have CS pain, but further work should reveal how they can be characterized., Limitations: Very few studies available., Conclusions: Literature about CS in patients with chronic idiopathic non-traumatic neck pain is rare and results from the available studies provide an inconclusive message. CS is not a characteristic feature of chronic idiopathic and non-traumatic neck pain, but can be present in some individuals of the population. In the future a subgroup with CS might be defined, but based on current knowledge it is not possible to characterize this subgroup. Such information is important in order to provide targeted treatment.

Background: A growing body of research has demonstrated that impaired central pain modulation or central sensitization (CS) is a crucial mechanism for the development of persistent pain in chronic whiplash-associated disorders (WAD) and fibromyalgia (FM) patients. Furthermore, there is increasing evidence for cognitive dysfunctions among these patients. In addition, chronic WAD and FM patients often report problems with health-related quality of life (QoL). Yet, there is limited research concerning the interrelations between cognitive performance, indices of CS, and health-related QoL in these patients., Objectives: (1) Examining the presence of cognitive impairment, CS, and limitations on health-related QoL in patients with chronic WAD and FM compared to healthy controls. (2) Examining interrelations between performance-based cognitive functioning, CS, and self-reported health-related QoL in these 3 study groups., Study Design: A case-control study was conducted., Setting: The present study took place at the University Hospital Brussels, the University of Brussels, and the University of Antwerp., Methods: Fifty-nine patients (16 chronic WAD patients, 21 FM patients, and 22 pain-free volunteers) filled out the Short Form 36 item Health Survey (SF-36), a self-reported psychosocial questionnaire, to assess health-related QoL. Next, they were subjected to various pain measurements (pressure hyperalgesia, deep-tissue hyperalgesia, temporal summation [TS], and conditioned pain modulation [CPM]). Finally, participants completed a battery of performance-based cognitive tests (Stroop task, psychomotor vigilance task [PVT], and operation span task [OSPAN])., Results: Significant cognitive impairment, bottom-up sensitization, and decreased health-related QoL were demonstrated in patients with chronic WAD and FM compared to healthy controls (P < 0.017). CPM was comparable between the 3 groups. Cognitive performance was significantly related to central pain modulation (deep-tissue hyperalgesia, TS, CPM) as well as to self-reported health-related QoL (P < 0.05). Decreased cognitive performance was related to deficient central pain modulation in healthy controls. Further, significant correlations between decreased cognitive performance and reduced health-related QoL were revealed among all study groups. Additionally, FM patients showed correlations between cognitive impairment and increased health-related QoL. Remarkably, impaired selective attention and working memory were related to less TS, whereas impaired sustained attention was correlated with dysfunctional CPM in FM patients., Limitations: Based on the current cross-sectional study no firm conclusions can be drawn on the causality of the relations., Conclusion: In conclusion, this paper has demonstrated significant cognitive deficits, signs of CS, and reduced health-related QoL in chronic WAD and FM patients compared to healthy individuals. Significant relations between cognitive performance and CS as well as health-related QoL were demonstrated. These results provide preliminary evidence for the clinical importance of objectively measured cognitive deficits in patients with chronic WAD and FM., Key Words: Chronic pain, fibromyalgia, whiplash, central sensitization, conditioned pain modulation, temporal summation, cognition, quality of life.