Establishing Central Sensitization-Related Symptom Severity Subgroups: A Multicountry Study Using the Central Sensitization Inventory.

OBJECTIVES: The goal of this study was to identify central sensitization-related symptom severity subgroups in a large multicountry sample composed of patients with chronic pain and pain-free individuals using the Central Sensitization Inventory (CSI). METHODS: A large, pooled international (N = 8 countries) sample of chronic pain patients plus healthy subjects (total N = 2,620) was randomly divided into two subsamples for cross-validation purposes. First, a hierarchical cluster analysis (HCA) was performed using CSI item-level data as clustering variables (test sample; N = 1,312). Second, a latent profile analysis (LPA) was conducted to confirm the optimal number of CSI clusters (validation sample; N = 1,308). Finally, to promote implementation in real-world clinical practice, we built a free online Central Sensitization Inventory Symptom Severity Calculator. RESULTS: In both HCA (N = 1,219 valid cases) and LPA (N = 1,245 valid cases) analyses, a three-cluster and three-profile solution, respectively, emerged as the most statistically optimal and clinically meaningful. Clusters were labeled as follows: (i) Low Level of CS-Related Symptom Severity, (ii) Medium Level of CS-Related Symptom Severity, and (iii) High Level of CS-Related Symptom Severity. CONCLUSIONS: Our results indicated that a three-cluster solution clearly captured the heterogeneity of the CSI data. The calculator might provide an efficient way of classifying subjects into the cluster groups. Future studies should analyze the extent to which the CSI cluster classification correlates with other patient-reported and objective signs and symptoms of CS in patients with chronic pain, their associations with clinical outcomes, health-related costs, biomarkers, (etc.), and responsiveness to treatment.

Does Pain Neuroscience Education and Cognition-Targeted Motor Control Training Improve Cervical Motor Output? Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: In the context of interventions aimed at reducing pain, disability, and maladaptive pain cognitions in chronic neck pain, it is hypothesized that patients who have greater symptom reduction possibly also demonstrate greater improvement in cervical motor output. Therefore, the aim of this study was to examine the effect of pain neuroscience education plus cognition-targeted motor control training on cervical motor output. METHODS: Impairments in cervical motor output were measured in 64 subjects with chronic neck pain using standardized tests. Cervical muscle strength, cervical mobility, balance, and cervical neuromuscular control were derived. To assess the differences between groups in response to treatment, a random-intercept linear mixed-models analysis, applying a diagonal covariance matrix, was used. RESULTS: A significant treatment × time interaction effect was found for neuromuscular control of the deep cervical flexors, favoring the experimental treatment at 3 months' follow-up (mean group difference: 1.982; 95% confidence interval 0.779, 3.185; large effect size d = 0.82). Significant main effects of time were found for the neuromuscular capacity of scapulothoracic muscles and for cervical mobility. No significant effects were found for balance, cervical muscle strength, or endurance of cervical flexors. CONCLUSION: Pain neuroscience education combined with cognition-targeted motor control training is not more effective than biomedically focused education and exercise therapy for improving cervical motor output in people with chronic neck pain. Our findings question the relative importance of factors such as pain, disability, and maladaptive pain cognitions on cervical motor output and the need to address it in treatment.

Associations between brain morphology and motor performance in chronic neck pain: A whole-brain surface-based morphometry approach.

Changes in brain morphology are hypothesized to be an underlying process that drive the widespread pain and motor impairment in patients with chronic neck pain. However, no earlier research assessed whole-brain cortical morphology in these patients. This case-control study assesses group-differences in whole-brain morphology between female healthy controls (HC; n = 34), and female patients with chronic idiopathic neck pain (CINP; n = 37) and whiplash-associated disorders (CWAD; n = 39). Additionally, the associations between whole-brain morphology and motor performance including balance, strength, and neuromuscular control were assessed. Cortical volume, thickness, and surface area were derived from high resolution T1-weighted images. T2*-weighted images were obtained to exclude traumatic brain injury. Vertex-wise general-linear-model-analysis revealed cortical thickening in the left precuneus and increased volume in the left superior parietal gyrus of patients with CINP compared to HC, and cortical thickening of the left superior parietal gyrus compared to HC and CWAD. Patients with CWAD showed a smaller cortical volume in the right precentral and superior temporal gyrus compared to HC. ANCOVA-analysis revealed worse neuromuscular control in CWAD compared to HC and CINP, and in CINP compared to HC. Patients with CWAD showed decreased levels of strength and sway area compared to CINP and HC. Partial correlation analysis revealed significant associations between the volume of the precentral gyrus, and neuromuscular control and strength together with an association between the volume of the superior temporal gyrus and strength. Our results emphasize the role of altered gray matter alterations in women with chronic neck pain, and its association with pain and motor impairment.

Convergent Validity of the Dutch Central Sensitization Inventory: Associations with Psychophysical Pain Measures, Quality of Life, Disability, and Pain Cognitions in Patients with Chronic Spinal Pain.

OBJECTIVE: Symptoms of central sensitization (CS) have been described in patients with chronic spinal pain (CSP). Although a gold standard to diagnose CS is lacking, psychophysical pain measures are often used. The Central Sensitization Inventory (CSI) is proposed as an alternative method and indirect tool for the evaluation of CS symptomatology. The aim of the current study was to evaluate the convergent validity of the CSI by investigating the association with psychophysical pain measures and self-reported measures of current pain intensity, quality of life, disability, and catastrophizing in CSP patients. METHODS: One hundred sixteen patients with nonspecific CSP were included in the present study. Patients completed the CSI, were subjected to pressure pain thresholds (PPTs) and a conditioned pain modulation (CPM) paradigm, and completed questionnaires for current pain intensity, quality of life, pain disability, and pain catastrophizing. RESULTS: Higher CSI scores were weakly correlated with lower PPTs (-0.276 ≤ r ≤ -0.237; all P ≤ 0.01) and not with CPM efficacy (r = 0.017; P = 0.858). Higher CSI scores were moderately correlated with higher current pain intensity (r = 0.320; P < 0.001), strongly correlated with lower physical (r = -0.617; P < 0.001) and emotional (r = -0.635; P < 0.001) quality of life, and moderately correlated with higher pain disability (r = 0.472; P < 0.001) and higher pain catastrophizing (r = 0.464; P < 0.001). CONCLUSION: The CSI was weakly associated with PPTs and not with CPM efficacy in CSP patients. Moderate to strong associations were found with current pain intensity, quality of life, disability, and catastrophizing. The current results illustrate that the CSI does not reflect a direct measure of CS, yet is a representation of general distress, possible originating from CS symptoms.

Psychological Distress and Widespread Pain Contribute to the Variance of the Central Sensitization Inventory: A Cross-Sectional Study in Patients with Chronic Pain.

OBJECTIVES: Central sensitization (CS) implies increased sensitivity of the nervous system, resulting in increased pain sensitivity as well as widespread pain. Recently, the Central Sensitization Inventory (CSI) was developed to assess symptoms of CS and central sensitivity syndromes. The aim of this study was to examine the convergent validity of the CSI by comparing the outcome to psychosocial factors and clinical features of CS. METHODS: In a cross-sectional explorative study, patients with chronic pain completed multiple questionnaires, including the CSI, Pain Catastrophizing Scale, and Symptom Checklist 90, for psychological distress, duration of pain, intensity of pain, widespread pain, and lateralization of pain. Based on bivariate correlations, relevant predictors of CS were selected and used to fit an exploratory structural equation model (SEM) of CS. RESULTS: In total, 114 patients with chronic pain were included, 56.1% being women. The average pain duration was 88 months. The mean total score on the CSI was 36.09 (15.26). The CSI was strongly related to known contributing and related factors of CS. SEM analysis showed that both psychological distress and widespread pain contributed significantly to the variance in symptoms of CS in patients with chronic pain. CONCLUSION: In this study, the convergent validity of the CSI was measured with demonstration of a strong relationship between contributing factors and clinical features of CS. These findings of convergent validity, considering former studies of the CSI, underline the use of the questionnaire in the clinical practice.

In the spine or in the brain? Recent advances in pain neuroscience applied in the intervention for low back pain.

Conservative, surgical and pharmacological strategies for chronic low back pain (CLBP) management offer at best modest effect sizes in reducing pain and related disability, indicating a need for improvement. Such improvement may be derived from applying contemporary pain neuroscience to the management of CLBP. Current interventions for people with CLBP are often based entirely on a "biomedical" or "psychological" model without consideration of information concerning underlying pain mechanisms and contemporary pain neuroscience. Here we update readers with our current understanding of pain in people with CLBP, showing that CLBP is not limited to spinal impairments, but is also characterised by brain changes, including functional connectivity reorganisation in several brain regions and increased activation in brain regions of the so-called 'pain matrix' (or 'pain connectome'). Indeed, in a subgroup of the CLBP population brain changes associated with the presence of central sensitisation are seen. Understanding the role of these brain changes in CLBP improves our understanding not only of pain symptoms, but also of prevalent CLBP associated comorbidities such as sleep disturbances and fear avoidance behaviour. Applying contemporary pain neuroscience to improve care for people with CLBP includes identifying relevant pain mechanisms to steer intervention, addressing sleep problems and optimising exercise and activity interventions. This approach includes cognitively preparing patients for exercise therapy using (therapeutic) pain neuroscience education, followed by cognition-targeted functional exercise therapy.

Efficacy of a modern neuroscience approach versus usual care evidence-based physiotherapy on pain, disability and brain characteristics in chronic spinal pain patients: protocol of a randomized clinical trial.

BACKGROUND: Among the multiple conservative modalities, physiotherapy is a commonly utilized treatment modality in managing chronic non-specific spinal pain. Despite the scientific progresses with regard to pain and motor control neuroscience, treatment of chronic spinal pain (CSP) often tends to stick to a peripheral biomechanical model, without targeting brain mechanisms. With a view to enhance clinical efficacy of existing physiotherapeutic treatments for CSP, the development of clinical strategies targeted at 'training the brain' is to be pursued. Promising proof-of-principle results have been reported for the effectiveness of a modern neuroscience approach to CSP when compared to usual care, but confirmation is required in a larger, multi-center trial with appropriate evidence-based control intervention and long-term follow-up.The aim of this study is to assess the effectiveness of a modern neuroscience approach, compared to usual care evidence-based physiotherapy, for reducing pain and improving functioning in patients with CSP. A secondary objective entails examining the effectiveness of the modern neuroscience approach versus usual care physiotherapy for normalizing brain gray matter in patients with CSP. METHODS/DESIGN: The study is a multi-center, triple-blind, two-arm (1:1) randomized clinical trial with 1-year follow-up. 120 CSP patients will be randomly allocated to either the experimental (receiving pain neuroscience education followed by cognition-targeted motor control training) or the control group (receiving usual care physiotherapy), each comprising of 3 months treatment. The main outcome measures are pain (including symptoms and indices of central sensitization) and self-reported disability. Secondary outcome measures include brain gray matter structure, motor control, muscle properties, and psychosocial correlates. Clinical assessment and brain imaging will be performed at baseline, post-treatment and at 1-year follow-up. Web-based questionnaires will be completed at baseline, after the first 3 treatment sessions, post-treatment, and at 6 and 12-months follow-up. DISCUSSION: Findings may provide empirical evidence on: (1) the effectiveness of a modern neuroscience approach to CSP for reducing pain and improving functioning, (2) the effectiveness of a modern neuroscience approach for normalizing brain gray matter in CSP patients, and (3) factors associated with therapy success. Hence, this trial might contribute towards refining guidelines for good clinical practice and might be used as a basis for health authorities' recommendations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02098005.

Exploring Interactions Between Sex, Pain Characteristics, Disability, and Quality of Life in People With Chronic Spinal Pain: A Structural Equation Model.

In people with nonspecific chronic spinal pain (nCSP), disability and quality of life are associated with clinical, cognitive, psychophysical, and demographic variables. However, evidence regarding the interactions between these variables is only limited to this population. Therefore, this study aims to explore path models explaining the multivariate contributions of such variables to disability and quality of life in people with nCSP. This secondary analysis uses baseline data from a randomized controlled trial including 120 participants with nCSP. Structural equation modeling was used to explore path models for the Pain Disability Index (PDI), the Short Form 36-item physical (SF-36 PC), and mental (SF-36 MC) component scores. All models included sex, pain catastrophizing, kinesiophobia, hypervigilance, and pain intensity. Additionally, the PDI and SF-36 PC models included pressure pain thresholds (PPTs) at the dominant pain site (ie, neck or low back). Significant associations were found between sex, pain cognitions, pain intensity, and PPTs. Only pain catastrophizing significantly directly influenced the PDI (P ≤ .001) and SF-36 MC (P = .014), while the direct effects on the SF-36 PC from kinesiophobia (P = .008) and pain intensity (P = .006) were also significant. However, only the combined effect of all pain cognitions on the SF-36 PC was mediated by pain intensity (P = .019). Our findings indicate that patients' pain-related cognitions have an adverse effect on their physical health-related quality of life via a negative influence on their pain intensity in people with nCSP. PERSPECTIVE: This secondary analysis details a network analysis confirming significant interactions between sex, pain cognitions, pain intensity, and PPTs in relation to disability and health-related quality of life in people with chronic spinal pain. Moreover, its findings establish the importance of pain cognitions and pain intensity for these outcomes. TRIALS REGISTRATION: Clinicaltrials.gov (NCT02098005).

Pain assessment in patellar tendinopathy using pain pressure threshold algometry: an observational study.

OBJECTIVE: Assessing pain in patellar tendinopathy (PT) is difficult to perform in a standardized way. With this study, we measured pain in athletes with PT by means of pain pressure threshold (PPT) algometry in a standardized manner. Subsequently, the goal of this study is to determine normative values for clinical use. DESIGN: Observational study. SETTING: Patients and healthy subjects were recruited from an outpatient clinic of a university medical center and at different sports clubs in northern Netherlands. SUBJECTS: A total of 234 athletes, 114 diagnosed with PT and 120 healthy controls, were included. OUTCOME MEASURES: PPT, Victorian Institute of Sport Assessment-Patellar tendinopathy questionnaire, and visual analog scale-pain. RESULTS: PPT scores of PT athletes with tendinopathy were significantly lower compared with healthy athletes (Mann-Whitney U-test; U = 293.5; P < 0.001). With a receiver operating characteristic (ROC) curve, the optimal cut-off point to distinguish between healthy athletes and PT athletes was calculated at 36.8 N. The area under the ROC curve was 0.98 (95% CI: 0.96-1.0). There was a positive predictive value of 96.5% that athletes with a PPT below 36.8 N. had PT. CONCLUSIONS: PPT algometry should be considered by clinicians as a pain assessment tool in patients with PT. The optimal cut-off point for the PPT to distinguish between PT athletes and healthy athletes was 36.8 N.

Influence of education level on the effectiveness of pain neuroscience education: A secondary analysis of a randomized controlled trial.

BACKGROUND: Current evidence supports the use of pain neuroscience education (PNE) in several chronic pain populations. However, the effects of PNE at group level are rather small and little is known about the influence of personal factors (e.g. level of education [LoE]). OBJECTIVE: To examine whether the effectiveness of PNE differs in chronic spinal pain (CSP) patients with high LOE (at least a Bachelor's degree) versus lower educated patients. METHOD: A total of 120 Belgian CSP patients were randomly assigned to the experimental (PNE) or control group (biomedical-focused neck/back school). Participants within each group were further subcategorized based on highest achieved LoE. ANOVA and Bonferroni post-hoc analyses were used to evaluate differences in effectiveness of the interventions between higher and lower educated participants. RESULTS: No differences between higher and lower educated participants were identified for pain-related disability. Significant interactions (P < .05) were found for kinesiophobia and several illness perceptions components. Bonferroni post-hoc analysis revealed a significant improvement in kinesiophobia (P < .001 and P < .002, medium effect sizes) and perceived negative consequences (P < .001 and P < .008, small effect sizes) in the PNE groups. Only the higher education PNE group showed a significant improvement in perceived illness cyclicity (P = .003, small effect size). Post-treatment kinesiophobia was significant lower in the higher educated PNE group compared to the higher educated control group (p < .001). CONCLUSION: Overall, the exploratory findings suggest no clinical meaningful differences in effectiveness of PNE between higher and lower educated people. PNE is effective in improving kinesiophobia and several aspects of illness perceptions regardless of LoE.

Assessment of Central Sensitization in Breast Cancer Survivors: Convergent Validity and Use of the Central Sensitization Inventory (CSI) and Its Short-Form as a Clustering Tool.

The Central Sensitization Inventory (CSI) measurement properties in patients having nonspecific, noncancer pain are well-established. However, studies examining the reliability and validity of either the CSI or the Central Sensitization Inventory short-form version (CSI-9) in breast cancer survivors (BCS) are scarce. The purpose was to evaluate convergent validity and internal consistency of the CSI and CSI-9. Additionally, the relevance of a new cluster calculator using the CSI was explored. The cross-sectional multi-center study included 65 BCS and 37 healthy volunteers. Patients filled out multiple questionnaires assessing pain, number of painful areas, anxiety, depression and quality of life. The relevance of a cluster calculator was explored by known-group comparisons and boxplot description. All hypotheses were formulated before data analysis. The majority of hypotheses on the correlations between the CSI or CSI-9 and other health outcomes were confirmed (22 out of 27). The CSI and CSI-9 have excellent (α = 0.92) and good (α = 0.86) internal consistency, respectively. The CSI cluster calculator might be an interesting tool to use to have a patient's overall condition snapshot. Generally, the study findings support the construct validity and internal consistency of the CSI, which underline the use of this self-reported instrument in BCS. The CSI-9 shows promising results, but should be further evaluated.

Influence of Baseline Kinesiophobia Levels on Treatment Outcome in People With Chronic Spinal Pain.

BACKGROUND: Pain neuroscience education (PNE) combined with cognition-targeted exercises is an effective treatment for people with chronic spinal pain (CSP). However, it is unclear why some patients benefit more from this treatment. We expect that patients with more pronounced maladaptive pain cognitions, such as kinesiophobia, might show poorer treatment responses. OBJECTIVE: The objective of this study was to assess the influence of baseline kinesiophobia levels on the treatment outcomes of PNE combined with cognition-targeted exercises in people with CSP. This study was a secondary analysis of a multicenter, double-blind, randomized controlled trial. METHODS: Outcome measures included a numeric rating scale for pain (NRS), the Pain Disability Index (PDI), quality of life (Medical Outcomes Study 36-Item Health Survey [SF-36]), Pain Catastrophizing Scale (PCS), and Pain Vigilance and Awareness Questionnaire (PVAQ). Regression models were built using treatment (PNE plus cognition-targeted exercises or neck/back school plus general exercises), baseline scores on the Tampa Scale for Kinesiophobia (TSK), and time (in months) as independent variables. RESULTS: A significant 3-way interaction effect was found for the models of PDI, PCS, PVAQ, and the SF-36 mental domain, with estimates of -0.01, -0.01, -0.01, and 0.07, respectively. A significant effect of baseline TSK scores was found for the physical domain of the SF-36 (estimate = -3.16). For the NRS, no significant effect of baseline TSK scores was found. CONCLUSION: Our findings indicate that PNE plus cognition-targeted exercises can successfully decrease the unfavorable influence of pretreatment kinesiophobia on disability, mental health, pain catastrophizing, and hypervigilance over time in people with CSP. Nevertheless, higher scores in pretreatment kinesiophobia might still be a key factor for the lack of improvement in pain catastrophizing and hypervigilance following treatment. Regardless of the followed treatment program, pretreatment kinesiophobia was also shown to significantly influence physical health in people with CSP. IMPACT: This study provides novel insight into the unfavorable influence of kinesiophobia on treatment outcomes in people with CSP, and how PNE plus cognition-targeted exercises can limit this impact. Because this is one of the first studies to research possible predictors of this experimental treatment, its findings motivate further exploration of other possible influencing factors for treatment success of PNE plus cognition-targeted exercises. LAY SUMMARY: People with chronic spinal pain and high levels of fear of movement were found to have worse treatment outcomes compared to people with low levels of fear of movement. However, our experimental treatment, which includes pain neuroscience education combined with exercise therapy that reintroduces specific movements patients might fear, can decrease this negative influence of fear of movement in these patients.

Gender Differences in the Association of Brain Gray Matter and Pain-Related Psychosocial Characteristics.

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.

Blended-Learning Pain Neuroscience Education for People With Chronic Spinal Pain: Randomized Controlled Multicenter Trial.

Background: Available evidence favors the use of pain neuroscience education (PNE) in patients with chronic pain. However, PNE trials are often limited to small sample sizes and, despite the current digital era, the effects of blended-learning PNE (ie, the combination of online digital media with traditional educational methods) have not yet been investigated. Objective: The study objective was to examine whether blended-learning PNE is able to improve disability, catastrophizing, kinesiophobia, and illness perceptions. Design: This study was a 2-center, triple-blind randomized controlled trial (participants, statistician, and outcome assessor were masked). Setting: The study took place at university hospitals in Ghent and Brussels, Belgium. Participants: Participants were 120 people with nonspecific chronic spinal pain (ie, chronic neck pain and low back pain). Intervention: The intervention was 3 sessions of PNE or biomedically focused back/neck school education (addressing spinal anatomy and physiology). Measurements: Measurements were self-report questionnaires (Pain Disability Index, Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, Illness Perception Questionnaire, and Pain Vigilance and Awareness Questionnaire). Results: None of the treatment groups showed a significant change in the perceived disability (Pain Disability Index) due to pain (mean group difference posteducation: 1.84; 95% CI = -2.80 to 6.47). Significant interaction effects were seen for kinesiophobia and several subscales of the Illness Perception Questionnaire, including negative consequences, cyclical time line, and acute/chronic time line. In-depth analysis revealed that only in the PNE group were these outcomes significantly improved (9% to 17% improvement; 0.37 ≤ Cohen d ≥ 0.86). Limitations: Effect sizes are small to moderate, which might raise the concern of limited clinical utility; however, changes in kinesiophobia exceed the minimal detectable difference. PNE should not be used as the sole treatment modality but should be combined with other treatment strategies. Conclusions: Blended-learning PNE was able to improve kinesiophobia and illness perceptions in participants with chronic spinal pain. As effect sizes remained small to medium, PNE should not be used as a sole treatment but rather should be used as a key element within a comprehensive active rehabilitation program. Future studies should compare the effects of blended-learning PNE with offline PNE and should consider cost-effectiveness.

Patients With Chronic Spinal Pain Benefit From Pain Neuroscience Education Regardless the Self-Reported Signs of Central Sensitization: Secondary Analysis of a Randomized Controlled Multicenter Trial.

BACKGROUND: Pain neuroscience education is effective in chronic pain management. Central sensitization (ie, generalized hypersensitivity) is often explained as the underlying mechanism for chronic pain, because of its clinical relevance and influence on pain severity, prognosis, and treatment outcome. OBJECTIVES: To examine whether patients with more or fewer symptoms of central sensitization respond differently to pain neuroscience education. DESIGN: A secondary analysis of a multicenter, triple-blind randomized controlled trial. SETTING: University Hospital Ghent and University Hospital Brussels, Belgium. PATIENTS: 120 persons with chronic spinal pain with high or low self-reported symptoms of central sensitization. INTERVENTIONS: Pain neuroscience education or neck/back school. Both interventions were delivered in 3 sessions: 1 group session, 1 online session, and 1 individual session. MAIN OUTCOME MEASURES: disability (primary), pain catastrophizing, kinesiophobia, illness perceptions, and hypervigilance. RESULTS: Pain disability did not change in any group (P = .242). Regarding secondary outcomes: significant interaction effects were found for pain catastrophizing (P-values: P = .02 to P = .05), kinesiophobia (P = .02), and several aspects of illness perceptions (chronicity: P = .002; negative consequences: P = .02; personal control: P = .02; and cyclicity: P = .02). Bonferroni post hoc analysis showed that only the pain neuroscience education group (high and low self-reported symptoms of central sensitization) showed a significant improvement regarding kinesiophobia (P < .001, medium effect sizes), perceived negative consequence (P = .004 and P < .001, small to medium effect sizes), and perceived cyclicity of the illness (P = .01 and P = .01, small effect sizes). Pain catastrophizing only significantly reduced in people with high self-reported central sensitization symptoms (P < .05). CONCLUSION: Pain neuroscience education is useful in all patients with chronic spinal pain as it improves kinesiophobia and the perceived negative consequences and cyclicity of the illness regardless the self-reported signs of central sensitization. Regarding pain catastrophizing, pain neuroscience education is more effective in patients with high self-reported symptoms of central sensitization. LEVEL OF EVIDENCE: I.

Effect of Pain Neuroscience Education Combined With Cognition-Targeted Motor Control Training on Chronic Spinal Pain: A Randomized Clinical Trial.

Importance: Effective treatments for chronic spinal pain are essential to reduce the related high personal and socioeconomic costs. Objective: To compare pain neuroscience education combined with cognition-targeted motor control training with current best-evidence physiotherapy for reducing pain and improving functionality, gray matter morphologic features, and pain cognitions in individuals with chronic spinal pain. Design, Setting, and Participants: Multicenter randomized clinical trial conducted from January 1, 2014, to January 30, 2017, among 120 patients with chronic nonspecific spinal pain in 2 outpatient hospitals with follow-up at 3, 6, and 12 months. Interventions: Participants were randomized into an experimental group (combined pain neuroscience education and cognition-targeted motor control training) and a control group (combining education on back and neck pain and general exercise therapy). Main Outcomes and Measures: Primary outcomes were pain (pressure pain thresholds, numeric rating scale, and central sensitization inventory) and function (pain disability index and mental health and physical health). Results: There were 22 men and 38 women in the experimental group (mean [SD] age, 39.9 [12.0] years) and 25 men and 35 women in the control group (mean [SD] age, 40.5 [12.9] years). Participants in the experimental group experienced reduced pain (small to medium effect sizes): higher pressure pain thresholds at primary test site at 3 months (estimated marginal [EM] mean, 0.971; 95% CI, -0.028 to 1.970) and reduced central sensitization inventory scores at 6 months (EM mean, -5.684; 95% CI, -10.589 to -0.780) and 12 months (EM mean, -6.053; 95% CI, -10.781 to -1.324). They also experienced improved function (small to medium effect sizes): significant and clinically relevant reduction of disability at 3 months (EM mean, -5.113; 95% CI, -9.994 to -0.232), 6 months (EM mean, -6.351; 95% CI, -11.153 to -1.550), and 12 months (EM mean, -5.779; 95% CI, -10.340 to -1.217); better mental health at 6 months (EM mean, 36.496; 95% CI, 7.998-64.995); and better physical health at 3 months (EM mean, 39.263; 95% CI, 9.644-66.882), 6 months (EM mean, 53.007; 95% CI, 23.805-82.209), and 12 months (EM mean, 32.208; 95% CI, 2.402-62.014). Conclusions and Relevance: Pain neuroscience education combined with cognition-targeted motor control training appears to be more effective than current best-evidence physiotherapy for improving pain, symptoms of central sensitization, disability, mental and physical functioning, and pain cognitions in individuals with chronic spinal pain. Significant clinical improvements without detectable changes in brain gray matter morphologic features calls into question the relevance of brain gray matter alterations in this population. Trial Registration: clinicaltrials.gov Identifier: NCT02098005.

Dimensionality and Reliability of the Central Sensitization Inventory in a Pooled Multicountry Sample.

Central sensitization (CS) involves the amplification of neural signaling within the central nervous system, which evokes pain hypersensitivity. The Central Sensitization Inventory (CSI) assesses 25 overlapping health-related symptom dimensions that have been reported to be associated with CS-related disorders. Previous studies have reported satisfactory test-retest reliability and internal consistency, but factor analyses have exhibited conflicting results in different language versions. The purpose of this cross-sectional study was to thoroughly examine the dimensionality and reliability of the CSI, with pooled data from 1,987 individuals, collected in several countries. The principal component analysis suggested that 1 general factor of CS best described the structure. A subsequent confirmatory factor analysis revealed that a bifactor model, which accounted for the covariance among CSI items, with regard to 1 general factor and 4 orthogonal factors, fit the CSI structure better than the unidimensional and the 4-factor models. Additional analyses indicated substantial reliability for the general factor (ie, Cronbach α = .92; ω = .95; and ω hierarchical = .89). Reliability results for the 4 specific factors were considered too low to be used for subscales. The results of this study clearly suggest that only total CSI scores should be used and reported. PERSPECTIVE: As far as we know, this is the first study that has examined the factor structure and reliability of the CSI in a large multicountry sample. The CSI is currently considered the leading self-report measure of CS-related symptoms worldwide.

Applying contemporary neuroscience in exercise interventions for chronic spinal pain: treatment protocol.

BACKGROUND: Nonspecific chronic spinal pain is a common problem within the chronic pain population and is characterized by high social, economic and personal impact. To date, therapists are still struggling in adequately treating these types of patients, as seen in the small and short-term benefits of frequently applied primary care treatments. It is remarkable that despite the well-documented presence of abnormalities in central nociceptive processing in nonspecific chronic spinal pain patients, the implementation of this knowledge in clinical practice is still nearly non-existent. METHODS: This paper provides the treatment protocol used in a large randomized controlled trial that aimed to assess the effectiveness of a modern neuroscience approach compared to usual care evidence-based physiotherapy. This comprehensive pain neuroscience treatment program combines pain neuroscience education and cognition-targeted exercise therapy. CONCLUSION: Based on previous small-scaled studies, this treatment protocol is expected to normalize central alterations by addressing central nervous system dysfunctions, psychological factors, as well as peripheral dysfunctions in a broader biopsychosocially-driven framework.

Differences Between Women With Traumatic and Idiopathic Chronic Neck Pain and Women Without Neck Pain: Interrelationships Among Disability, Cognitive Deficits, and Central Sensitization.

Background: To date, a clear differentiation of disability, cognitive deficits, and central sensitization between chronic neck pain of a traumatic nature and that of a nontraumatic nature is lacking. Objective: This study aimed to examine differences in disability, cognitive deficits, and central sensitization between women with traumatic and idiopathic (nontraumatic) chronic neck pain and women who were healthy. In addition, interrelationships among these variables were investigated. Design: This was a case-control study. Methods: Ninety-five women (28 women who were healthy [controls], 35 women with chronic idiopathic neck pain [CINP], and 32 women with chronic whiplash-associated disorders [CWAD] [traumatic]) were enrolled in the study. First, all participants completed standardized questionnaires to investigate pain-related disability and health-related quality of life. Next, cognitive performance was assessed. Finally, pressure pain thresholds and conditioned pain modulation were examined to investigate central sensitization. Results: Pain-related disability, reduced health-related quality of life, and cognitive deficits were present in participants with CWAD and, to a significantly lesser extent, in participants with CINP. Local hyperalgesia was demonstrated in participants with CWAD and CINP but not in women who were healthy. However, distant hyperalgesia and decreased conditioned pain modulation efficacy were shown only in participants with CWAD; this result is indicative of the presence of central sensitization. Moderate to strong Spearman correlations (ρ=.456-.701) among disability, cognitive deficits, and hyperalgesia (local and distant) were observed in participants with CWAD. In participants with CINP, only local hyperalgesia and subjective cognitive deficits were moderately (ρ=.463) correlated. Limitations: No conclusions about the causality of the observed correlations can be drawn. Conclusions: This innovative research revealed important differences between women with CWAD and women with CINP and thus provided evidence of the clinical importance of distinguishing the assessment and rehabilitation approaches for both pain conditions.

Does Conservative Treatment Change the Brain in Patients with Chronic Musculoskeletal Pain? A Systematic Review.

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.