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Background: To address the need for a better treatment of chronic whiplash associated disorders (WAD), a contemporary neuroscience approach can be proposed., Objective: To examine the effectiveness of a contemporary neuroscience approach, comprising pain neuroscience education, stress management, and cognition-targeted exercise therapy versus conventional physical therapy for reducing disability (primary outcome measure) and improving quality of life and reducing pain, central sensitization, and psychological problems (secondary outcome measures) in people with chronic WAD., Methods: The study is a multi-center, two-arm randomized, controlled trial with 1-year follow-up and will be performed in two university-based and one regional hospital. People with chronic WAD (n=120) will be recruited. The experimental group will receive pain neuroscience education followed by cognition-targeted exercise therapy, and stress management. The control group will receive biomedically focused education followed by graded and active exercise therapy focusing on muscle endurance, strength, and flexibility, and ergonomic principles. The treatment will have a duration of 16 weeks. Functional status (Neck Disability Index) is the primary outcome measure. Secondary outcome measures include quality of life, pain, central sensitization, and psychological and socio-economic factors. In addition, electroencephalography will measure brain activity at rest and during a conditioned pain modulation paradigm. Assessments will take place at baseline, immediately post-treatment and at 6 and 12 months follow-up., Conclusions: This study will examine whether a contemporary neuroscience approach is superior over conventional physical therapy for improving functioning, quality of life, and reducing pain, central sensitization, and psychological problems in people with chronic WAD., (Copyright © 2020 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Two factors related to the continuation of persistent pain are pain catastrophizing and illness perceptions. Pain neuroscience education is known to positively influence both in patients with persistent pain. As the integration of pain neuroscience education in monodisciplinary physiotherapy treatments is effective, integration in transdisciplinary cognitive-behavioral treatments seems recommendable. When doing so, the moderating effect of pain catastrophizing and perceptions on treatment results have to be examined, as these provide valuable information under which conditions treatment works. A bottom-up retrospective observational study evaluated the changes in clinical outcomes, and relationships between clinical outcomes and cognitive and emotional factors in patients with persistent pain. Multiple regression analysis, PROCESS macro, explored the moderating effects of pain catastrophizing on the relationship between illness perceptions and self-reported symptoms of central sensitization. In total, 78 patients were included in the study. A correlation between pretreatment scores and change scores in illness perceptions and self-reported symptoms of central sensitization following treatment were found (resp. R-sq 0.407, F(10,99) = 0.638, P = 0.000; R-sq 0.361, F(5, 54) = 0.609, P = 0.000; and R-sq 0.314, F(4,55) = 0.560, P = 0.00), however, moderation of pain catastrophizing scores on these correlations was not found. Even though an association between changes in pain catastrophizing and illness perceptions in patients with persistent pain was found, the direction or strength between the changes in illness perceptions and changes in self-reported symptoms of central sensitization was not influenced by pretreatment scores of pain catastrophizing.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Few treatment programs for chronic pain nowadays take a dietary pattern or adipose status into account., Areas Covered: An important role of neuroinflammation in chronic pain is now well established, at least in part due to increased central nervous system glial activation. Based on preclinical studies, it is postulated that the interaction between nutrition and central sensitization is mediated via bidirectional gut-brain interactions. This model of diet-induced neuroinflammation and consequent central sensitization generates a rationale for developing innovative treatments for patients with chronic pain. Methods: An umbrella approach to cover the authors' expert opinion within an evidence-based viewpoint., Expert Opinion: A low-saturated fat and low-added sugar dietary pattern potentially decreases oxidative stress, preventing Toll-like receptor activation and subsequent glial activation. A low-saturated fat and low-added sugar diet might also prevent afferent vagal nerve fibers sensing the pro-inflammatory mediators that come along with a high-(saturated) fat or energy-dense dietary pattern, thereby preventing them to signal peripheral inflammatory status to the brain. In addition, the gut microbiota produces polyamines, which hold the capacity to excite N-methyl-D-aspartate receptors, an essential component of the central nervous system sensitization. Hence, a diet reducing polyamine production by the gut microbiota requires exploration as a therapeutic target for cancer-related and non-cancer chronic pain.

Background: Sensitivity-related trait characteristics involving physical and emotional sensitivities and high trait anxiety personality types have been observed in individuals with nonspecific chronic low back pain (NSCLBP). High trait sensitivity to sensory stimulation combined with interpretation biases based on personality type may contribute to the development of central sensitization (CS) symptoms. To date, there is limited research that has considered both sensitivity levels and personality type in NSCLBP with CS. The purpose of this study was to investigate (1) relationships between trait sensory profiles, trait anxiety, and CS symptoms, and (2) the predictive capacity of sensory profiles, trait anxiety, and personality types on CS symptoms in people with NSCLBP., Methods: This was a cross-sectional observational study using 4 self-report measures on adults (N = 165, mean age = 45 ± 12 [standard deviation] years) from physiotherapy clinics in England, Ireland, and New Zealand. Inclusion: NSCLBP > 6 months, age 18 to 64 years, predominant CS pain presentation, no other pathology. Parametric and nonparametric correlation statistics and regression analyses were used., Results: Positive correlations were found between central sensitization inventory (CSI) scores and sensory hypersensitivity profiles and trait anxiety. CSI score increases could be predicted by sensory-sensitive, low-registration profiles; trait anxiety scores; and extreme defensive high anxious personality type., Conclusions: Trait sensory hyper- and/or hyposensitivity and high trait anxiety-related personality type characteristics predict the extent of CS symptoms in people with NSCLBP. Further investigation is required to establish causality between these characteristics and CS symptoms., (© 2019 World Institute of Pain.)

Background: Mechanical quantitative sensory testing (QST) assesses sensory functioning and detects functional changes in (central) nociceptive processing. It has been hypothesized that these functional changes might be apparent in people with nonspecific low back pain (LBP), although the results are mixed., Objective: The aim of this systematic review was to examine whether sensory function, measured with QST, was altered in people with nonspecific LBP., Methods: This systematic review was conducted according to PRISMA guidelines. Six databases were searched for relevant literature. Studies comparing mechanical QST measures involving people with subacute and chronic LBP and healthy controls were included if (1) pressure pain thresholds (PPTs), (2) temporal summation, or (3) conditioned pain modulation were reported. Risk of bias was assessed using the Newcastle-Ottawa scale. When possible, the results from different studies were pooled., Results: Twenty-four studies were included. Scores on the Newcastle-Ottawa scale varied between 1 and 6 points. People with nonspecific LBP, compared to healthy controls, had significantly lower PPTs at remote sites and increased temporal summation at the lower back. The PPTs measured at the scapula were significantly lower in patients with nonspecific LBP than in healthy controls (pooled mean difference, 119.2 kPa; 95% confidence interval: 91.8, 146.6 kPa; P <.001)., Conclusion: The PPT measurements at remote body parts were significantly lower in people with nonspecific LBP compared with healthy controls. Temporal summation and conditioned pain modulation measurements had mixed outcomes., Level of Evidence: Therapy, level 3a. J Orthop Sports Phys Ther 2019;49(10):698-715. Epub 23 Aug 2019. doi:10.2519/jospt.2019.8876 .

Background: Individuals with nonspecific chronic low back pain (NSCLBP) and central sensitization (CS) exhibit sensory hypersensitivity that may be related to pre-existing trait characteristics. Sensory profiles and trait anxiety-related characteristics have sensory sensitivity in common with CS., Objectives: The objectives of this study were 1) to observe the prevalence of 4 personality types and extreme scores of 4 trait sensory profiles in people with NSCLBP and predominant CS; and 2) to compare these between 2 subgroups based on high and low self-reported CS symptoms., Study Design: An international cross-sectional observational study was undertaken., Setting: Adults (n = 165; mean age = 45 ± 12 standard deviation) were recruited from physiotherapy clinics across 3 countries and 2 continents., Methods: The inclusion criteria were: NSCLBP, aged 18-64 years, with clinically identified predominant CS pain, without specific pathology. The outcome measures were: Central Sensitization Inventory (CSI), Adolescent/Adult Sensory Profile, State/Trait Anxiety Inventory, and Marlowe Crowne Social Desirability Scale. Descriptive and comparative statistics were used., Results: CSI scores ranged from 19-79 (mean = 50). There was a high prevalence of extreme 1) trait sensory hyper- and, unexpectedly, hyposensitivity profile scores (P < 0.001) and Defensive High Anxious personality type (P < 0.01) in the high-CSI (CSI>= 40; 78%) subgroup, and 2) trait sensory hyposensitivity profile scores (P < 0.01) and Repressor personality type (P < 0.01) in the low-CSI subgroup (CSI < 40; 22%)., Limitations: Self-report measures only were used; limited demographics., Conclusions: To our knowledge, these results are the first to demonstrate extreme trait sensory profiles and personality types in people with NSCLBP and predominant CS. A subgroup who reports low levels of CS symptoms may have a hyposensitive sensory profile and Repressor personality type. Further study is required to investigate the extent to which these trait characteristics may predict CS symptoms in people with NSCLBP., Key Words: Central sensitization, nonspecific chronic low back pain, prevalence of extreme trait characteristics, sensory profiles, trait anxiety-related personality types.

Competing Interests: Competing interests: None declared.

Introduction: The differentiation between acute and chronic pain can be insufficient for appropriate pain management. The aim of this study was to evaluate the prevalence of the predominant pain type (nociceptive, neuropathic, or central sensitization [CS] pain) in breast cancer survivors (BCS) with chronic pain. The secondary aims were to examine (1) differences in health-related quality of life (HRQoL) between the different pain groups; and (2) the associations between patient-, disease-, and treatment-related factors and the different pain types., Methods: To determine the prevalence of the predominant type of pain, a recently proposed classification system was used. BCS were asked to complete the VAS for pain, Douleur Neuropathique 4 Questionnaire, Margolis Pain Diagram, Central Sensitization Inventory, and Short Form 36 (SF-36)., Results: Ninety-one BCS participated, among whom 25.3% presented neuropathic pain, 18.7% nociceptive pain, and 15.4% CS pain. Mixed pain was found in 40.6%. A significant intergroup difference in HRQoL was found for SF-36 "general health" (P = 0.04). The odds for the presence of CS rather than nociceptive pain are 26 times higher in patients exposed to hormone therapy in comparison to the nonexposed (odds ratio 25.95, 95% confidence interval 1.33 to 504.37, P = 0.03)., Conclusion: Neuropathic pain is most frequent in BCS. Strong associations were found between CS pain and hormone therapy., (© 2018 World Institute of Pain.)

Objective: Hyperexcitability of the central nervous system plays an important role in the development and maintenance of chronic pain in adults. This knowledge has led to improved treatment strategies within this population. In children, however, research on the presence of central hyperexcitability is scarce. To further investigate this topic in children with chronic pain, there is a need for a clear literature overview., Design: Systematic review., Methods: The literature search was performed using the electronic databases PubMed and Web of Science. An article was considered eligible if it included children (age two to 12 years) diagnosed with chronic pain. Articles had to report original research outcomes related to central hyperexcitability, and a comparison with a healthy control group was necessary. Characteristics of the study sample, the assessment, and conclusions regarding central hyperexcitability were extracted from each included article., Results: Twelve case-control studies were included with moderate to good methodological quality (510 children with chronic pain and 670 healthy controls). After summarizing the articles' results on indices of central hyperexcitability, we concluded that secondary hyperalgesia might be present in children with recurrent abdominal pain, juvenile fibromyalgia, and juvenile idiopathic arthritis. Preliminary evidence exists for altered cortical nociceptive processing in children with migraine and recurrent abdominal pain., Conclusion: Based on the results of this review, central hyperexcitability might be present in in several pediatric chronic pain conditions. Further research on other manifestations of central hyperexcitability (e.g., bottom-up and top-down mechanisms and nociceptive brain changes) is necessary to provide firm evidence about its presence in children with chronic pain.

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., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Background: Despite growing awareness of the contribution of central pain mechanisms to knee osteoarthritis pain in a subgroup of patients, routine evaluation of central sensitization is yet to be incorporated into clinical practice., Aim: The objective of this perspective is to design a set of clinical descriptors for the recognition of central sensitization in patients with knee osteoarthritis that can be implemented in clinical practice., Methods: A narrative review of original research papers was conducted by nine clinicians and researchers from seven different countries to reach agreement on clinically relevant descriptors., Results: It is proposed that identification of a dominance of central sensitization pain is based on descriptors derived from the subjective assessment and the physical examination. In the former, clinicians are recommended to inquire about intensity and duration of pain and its association with structural joint changes, pain distribution, behavior of knee pain, presence of neuropathic-like or centrally mediated symptoms and responsiveness to previous treatment. The latter includes assessment of response to clinical test, mechanical hyperalgesia and allodynia, thermal hyperalgesia, hypoesthesia and reduced vibration sense., Conclusions: This article describes a set of clinically relevant descriptors that might indicate the presence of central sensitization in patients with knee osteoarthritis in clinical practice. Although based on research data, the descriptors proposed in this review require experimental testing in future studies. Implications for Rehabilitation Laboratory evaluation of central sensitization for people with knee osteoarthritis is yet to be incorporated into clinical practice. A set of clinical indicators for the recognition of central sensitization in patients with knee osteoarthritis is proposed. Although based on research data, the clinical indicators proposed require further experimental testing of psychometric properties.

Background and Objective: Central sensitization (CS) is a phenomenon associated with several medical diagnoses, including postcancer pain, low back pain, osteoarthritis, whiplash, and fibromyalgia. CS involves an amplification of neural signaling within the central nervous system that results in pain hypersensitivity. The purpose of this systematic review was to gather published studies of a widely used outcome measure (the Central Sensitization Inventory [CSI]), determine the quality of evidence these publications reported, and examine the measurement properties of the CSI., Databases and Data Treatment: Four databases were searched for publications from 2011 (when the CSI was developed) to July 2017. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was applied to evaluate methodological quality and risk of bias. In instances when COSMIN did not offer a scoring system for measurement properties, qualitative analyses were performed., Results: Fourteen studies met inclusion criteria. Quality of evidence examined with the COSMIN checklist was determined to be good to excellent for all studies for their respective measurement property reports. Interpretability measures were consistent when publications were analyzed qualitatively, and construct validity was strong when examined alongside other validated measures relating to CS., Conclusions: An assessment of the published measurement studies of the CSI suggest the tool generates reliable and valid data that quantify the severity of several symptoms of CS., (© 2017 World Institute of Pain.)

Background: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown., Methods: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten chronic fatigue syndrome (CFS)/fibromyalgia (FM) patients, 11 rheumatoid arthritis (RA) patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/mL Naloxone) and placebo (2 mL Aqua) group. Pressure pain thresholds (PPTs) and temporal summation at the Trapezius and Quadriceps were assessed by algometry. Conditioned pain modulation (CPM) efficacy and deep tissue pain pressure were assessed by adding ischemic occlusion at the opposite upper arm., Results: Deep tissue pain pressure was lower and temporal summation higher in CFS/FM (P = 0.002 respectively P = 0.010) and RA patients (P = 0.011 respectively P = 0.047) compared to controls at baseline. Morphine had only a positive effect on PPTs in both patient groups (P time = 0.034). Accordingly, PPTs increased after placebo (P time = 0.015), and no effects on the other pain parameters were objectified. There were no significant effects of naloxone nor nocebo on PPT, deep tissue pain, temporal summation or CPM in the control group., Conclusions: This study revealed anti-hyperalgesia effects of morphine in CFS/FM and RA patients. Nevertheless, these effects were comparable to placebo. Besides, neither morphine nor naloxone influenced deep tissue pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA., (© 2017 World Institute of Pain.)

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., (Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2017 World Institute of Pain.)

Objective: The objective of this cross-sectional study was to analyze the relationship between symptoms of central sensitization (CS) and important cognitive behavioral and psychosocial factors in a sample of patients with chronic nonspecific low back pain., Methods: Participants with chronic nonspecific low back pain for at least 3 months were included in the study. They completed several questionnaires and a functional test. Pearson's correlation was used to analyze associations between symptoms of CS and pain behavior, functioning, pain, pain catastrophizing, kinesiophobia, and illness perceptions. Additionally, a between-group analysis was performed to compare patients with and without clinically relevant symptoms of CS., Results: Data from 38 participants were analyzed. Significant associations were found between symptoms of CS and all other outcomes, especially current pain (r = 0.510, P = .001), mean pain during the past 7 days (r = 0.505, P = .001), and pain catastrophizing (r = 0.518, P = .001). Patients with clinically relevant symptoms of CS scored significantly worse on all outcomes compared with persons without relevant symptoms of CS, except on functioning (P = .128)., Conclusions: Symptoms of CS were significantly associated with psychosocial and cognitive behavioral factors. Patients exhibiting a clinically relevant degree of symptoms of CS scored significantly worse on most outcomes, compared with the subgroup of the sample with fewer symptoms of CS., (Copyright © 2017. Published by Elsevier Inc.)

Background: Altered central pain modulation is the predominant pain mechanism in a proportion of chronic musculoskeletal pain disorders and is associated with poor outcomes. Although existing studies predict poor outcomes such as persistent pain and disability, to date there is little consensus on what factors specifically predict altered central pain modulation., Objectives: To review the existing literature on the predictive factors specifically for altered central pain modulation in musculoskeletal pain populations., Study Design: This is a systematic review in accordance with supplemented PRISMA guidelines., Methods: A systematic search was performed by 2 mutually blinded reviewers. Relevant articles were screened by title and abstract from Medline, Embase, PubMed, CINAHL, and Web of Science electronic databases. Alternative sources were also sought to locate missed potential articles. Eligibility included studies published in English, adults aged 18 to 65, musculoskeletal pain, baseline measurements taken at the pre-morbid or acute stage, > 3-month follow-up time after pain onset, and primary outcome measures specific to altered central pain modulation. Studies were excluded where there were concurrent diseases or they were non-predictive studies. Risk of bias was assessed using the quality in prognostic studies (QUIPS) tool. Study design, demographics, musculoskeletal region, inclusion/exclusion criteria, measurement timelines, predictor and primary outcome measures, and results were extracted. Data were synthesized qualitatively and strength of evidence was scored using the grading of recommendations, assessment, development, and evaluations (GRADE) scoring system., Results: Nine eligible articles were located, in various musculoskeletal populations (whiplash, n = 2; widespread pain, n = 5; temporomandibular disorder, n = 2). Moderate evidence was found for 2 predictive factors of altered central pain modulation: 1) high sensory sensitivity (using genetic testing or quantitative sensory tests), and 2) psychological factors (somatization and poor self-expectation of recovery), at a pre-morbid or acute stage baseline., Limitations: At the times of the article publications, the current definitions and clinical guidelines for identifying altered central pain modulation were not yet available. Careful interpretation of the information provided using current knowledge and published guidelines was necessary to extract information specific to altered central pain modulation in some of the studies, avoiding unwarranted assumptions., Conclusions: Premorbid and acute stage high sensory sensitivity and/or somatization are the strongest predictors of altered central pain modulation in chronic musculoskeletal pain to date. This is the first systematic review specifically targeting altered central pain modulation as the primary outcome in musculoskeletal pain populations. Early identification of people at risk of developing chronic pain with altered central pain modulation may guide clinicians in appropriate management, diminishing the burden of persistent pain on patients and heath care providers alike. Systematic Review Registration no.: PROSPERO 2015:CRD42015032394.Key words: Predictive factors, pre-morbid and acute stage baselines, altered central pain modulation, chronic musculoskeletal pain, sensory processing, somatization.

Modern pain neuroscience has substantially improved our understanding of the (development of) chronic musculoskeletal pain. The time has come for orthopaedic and sports physical therapists to implement modern pain neuroscience in specialized, but definitely also in primary, care settings, including the role of central sensitization (CS) in amplifying and explaining the presence of the pain experience. Central sensitization dominates the clinical picture in a subgroup of the musculoskeletal pain population, ranging from tennis elbow over shoulder pain to osteoarthritis and whiplash. Applying modern pain neuroscience to clinical practice implies (1) recognizing those patients having predominant CS pain, and (2) accounting for CS when designing the treatment plan in those with predominant CS pain. Future work in this area should (1) examine the validity of the proposed clinical classification algorithm for identifying CS pain in patients with orthopaedic and sports injuries, and (2) explore evidence-based treatment options for patients having predominant CS pain. J Orthop Sports Phys Ther 2016;46(12):1024-1028. doi:10.2519/jospt.2016.0612.

Background: Expanded distribution of pain is considered a sign of central sensitization (CS). The relationship between recording of symptoms and CS in people with knee osteoarthritis (OA) has been poorly investigated., Objective: The aim of this study was to examine whether the area of pain assessed using pain drawings relates to CS and clinical symptoms in people with knee OA., Design: This was a cross-sectional study., Methods: Fifty-three people with knee OA scheduled to undergo primary total knee arthroplasty were studied. All participants completed pain drawings using a novel digital device, completed self-administration questionnaires, and were assessed by quantitative sensory testing. Pain frequency maps were generated separately for women and men. Spearman correlation coefficients were computed to reveal possible correlations between the area of pain and quantitative sensory testing and clinical symptoms., Results: Pain frequency maps revealed enlarged areas of pain, especially in women. Enlarged areas of pain were associated with higher knee pain severity (rs=.325, P<.05) and stiffness (rs=.341, P<.05), lower pressure pain thresholds at the knee (rs=-.306, P<.05) and epicondyle (rs=-.308, P<.05), and higher scores with the Central Sensitization Inventory (rs=.456, P<.01). No significant associations were observed between the area of pain and the remaining clinical symptoms and measures of CS., Limitations: Firm conclusions about the predictive role of pain drawings cannot be drawn. Further evaluation of the reliability and validity of pain area extracted from pain drawings in people with knee OA is needed., Conclusion: Expanded distribution of pain was correlated with some measures of CS in individuals with knee OA. Pain drawings may constitute an easy way for the early identification of CS in people with knee OA, but further research is needed., (© 2016 American Physical Therapy Association.)

The aim of this study is to systematically review whether the presence of altered central pain modulation pre-surgical influences outcome after total knee replacement (TKR) in patients with knee osteoarthritis (OA), and if so which indices of central pain modulation predict poor outcome after TKR. To identify relevant articles, PubMed and Web of Science were searched. The search strategy was a combination of key words related to "Knee Osteoarthritis and Total Knee Replacement", "Central Pain Modulation" and "Post-Surgical Outcome Measures". Articles fulfilling the inclusion criteria were screened for methodological quality and results were analyzed and summarized. Sixteen prospective cohort studies were included. Strong evidence is available that presence of catastrophic thinking and poor coping strategies predict more pain after TKR and that there is no association between fear of movement and post-surgical pain or function. Evidence on other psychosocial influences is limited or conflicting. Literature on the influence of other signs of altered central pain modulation on post-surgical outcome is scarce. It is plausible that pre-surgical signs of altered central pain modulation, such as joint pain at rest or widespread pain sensitization, predict more post-surgical pain. Surgeons should be attentive for patients with signs of altered central pain modulation before surgery as they might be at risk for unfavorable outcome. A broader therapeutic approach aiming to desensitize the central nervous system can be adapted in these patients. Further research is however needed to identify the influence of central pain modulation pre-surgical in predicting outcome after TKR., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Introduction: Hyperexcitability of the central nervous system has been suggested to play an important role in pain experienced by patients with unilateral shoulder pain. A systematic literature review following the PRISMA guidelines was performed to evaluate the existing evidence related to the presence of central sensitization in patients with unilateral shoulder pain of different etiologies including those with chronic subacromial impingement syndrome. Studies addressing neuropathic pain (e.g., post-stroke shoulder pain) were not considered., Methods: Electronic databases PubMed, EBSCO, and Web of Science were searched to identify relevant articles using predefined keywords regarding central sensitization and shoulder pain. Articles were included till September 2013. Full-text clinical reports addressing studies of central sensitization in human adults with unilateral shoulder complaints including those diagnosed with subacromial impingement syndrome were included and screened for methodological quality by two independent reviewers., Results: A total of 10 articles were retrieved for quality assessment and data extraction. All studies were cross-sectional (case-control) or longitudinal in nature. Different subjective and objective parameters, considered manifestations of central sensitization, were established in subjects with unilateral shoulder pain of different etiologies, including those receiving a diagnosis of subacromial impingement syndrome. Overall results suggest that, although peripheral mechanisms are involved, hypersensitivity of the central nervous system plays a role in a subgroup within the shoulder pain population., Conclusions: Although the majority of the literature reviewed provides emerging evidence for the presence of central sensitization in unilateral shoulder pain (including those diagnosed with subacromial impingement syndrome), our understanding of the role central sensitization plays in the shoulder pain population is still in its infancy. Future studies with high methodical quality are therefore required to investigate this further., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

Traditional understanding of osteoarthritis-related pain has recently been challenged in light of evidence supporting a key role of central sensitization in a subgroup of this population. This fact may erroneously lead musculoskeletal therapists to conclude that hands-on interventions have no place in OA management, and that hands-off interventions must be applied exclusively. The aim of this paper is to encourage clinicians in finding an equilibrium between hands-on and hands-off interventions in patients with osteoarthritis-related pain dominated by central sensitization. The theoretical rationale for simultaneous application of manual therapy and pain neuroscience education is presented. Practical problems when combining these interventions are also addressed. Future studies should explore the combined effects of these treatment strategies to examine whether they increase therapeutic outcomes against current approaches for chronic osteoarthritis-related pain., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Hyperexcitability of the central nervous system (CNS) has been suggested to play an important role in the chronic pain experienced by osteoarthritis (OA) patients. A systematic review following PRISMA guidelines was performed to evaluate the existing evidence from the literature related to the presence of central sensitization (CS) in patients with OA.Electronic databases PubMed and Web of Science were searched to identify relevant articles using pre-defined keywords regarding CS and OA. Full-text clinical reports addressing studies of CS in human adults with chronic complaints due to osteoarthritis were included and screened for methodological quality by two independent reviewers. From the 40 articles that were initially eligible for methodological quality assessment, 36 articles achieved sufficient scores and therefore were discussed. The majority of these studies were case-control studies and addressed OA of the knee joint. Different subjective and objective parameters considered manifestations of CS, which have been previously reported in other chronic pain conditions such as whiplash or rheumatoid arthritis, were established in subjects with OA pain. Overall results suggest that, although peripheral mechanisms are involved in OA pain, hypersensitivity of the CNS plays a significant role in a subgroup of subjects within this population. Although the majority of the literature provides evidence for the presence of CS in chronic OA pain, clinical identification and treatment of CS in OA is still in its infancy, and future studies with good methodological quality are necessary., (© 2014 European Pain Federation - EFIC®)

Background: The awareness is growing that central sensitization is of prime importance for the assessment and management of chronic pain, but its classification is challenging clinically since no gold standard method of assessment exists., Objectives: Designing the first set of classification criteria for the classification of central sensitization pain., Methods: A body of evidence from original research papers was used by 18 pain experts from 7 different countries to design the first classification criteria for central sensitization pain., Results: It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory)., Limitations: Although based on direct and indirect research findings, the classification algorithm requires experimental testing in future studies., Conclusion: Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain.

Introduction: Central sensitization (CS) is present in a variety of chronic pain disorders, including whiplash, temporomandibular disorders, low back pain, osteoarthritis, fibromyalgia, headache, lateral epicondylalgia among others. In spite of our increased understanding of the mechanisms involved in CS pain, its treatment remains a challenging issue., Areas Covered: An overview of the treatment options we have for desensitising the CNS in patients with CS pain is provided. These include strategies for eliminating peripheral sources of nociception, as well as pharmacotherapy and conservative interventions that primarily address top-down (i.e., brain-orchestrated) mechanisms., Expert Opinion: A combination of different strategies, each targeting a different 'desensitizing' mechanism, might prove superior over monotherapies. Such combined therapy may include both bottom-up and top-down (e.g., opioids, combined μ-opioid receptor agonist and noradrenaline reuptake inhibitor drugs) strategies. Topically applied analgesic therapies have strong potential for (temporally) decreasing peripheral nociceptive input (bottom-up approach). Targeting metabolic (e.g., ketogenic diets) and neurotrophic factors (e.g., decreasing brain-derived neurotrophic factor) are promising new avenues for diminishing hyperexcitability of the CNS in central sensitization pain patients. Addressing conservative treatments, pain neuroscience education, cognitive behavioural therapy and exercise therapy are promising treatments for CS pain.

Background and Objectives: It has been suggested that sensitization of the central nervous system plays an important role in the development and maintenance of chronic (pain) complaints experienced by whiplash patients. According to the PRISMA guidelines, a systematic review was performed to screen and evaluate the existing clinical evidence for the presence of central sensitization in chronic whiplash. DATABASES AND DATA TREATMENT: Predefined keywords regarding central sensitization and chronic whiplash were combined in electronic search engines PubMed and Web of Science. Full text clinical reports addressing studies of central sensitization in human adults with chronic complaints due to a whiplash trauma were included and reviewed on methodological quality by two independent reviewers., Results: From the 99 articles that were identified, 24 met the inclusion criteria, and 22 articles achieved sufficient scores on methodological quality and were discussed. These studies evaluated the sensitivity to different types of stimuli (mechanical, thermal, electrical). Findings suggest that although different central mechanisms seem to be involved in sustaining the pain complaints in whiplash patients, hypersensitivity of the central nervous system plays a significant role. Persistent pain complaints, local and widespread hyperalgesia, referred pain and (thoracic) allodynia, decreased spinal reflex thresholds, inefficient diffuse noxious inhibitory controls activation and enhanced temporal summation of pain were established in chronic whiplash patients., Conclusions: Although the majority of the literature provides evidence for the presence of central sensitization in chronic whiplash, underlying mechanisms are still unclear and future studies with good methodological quality are necessary. In addition, international guidelines for the definition, clinical recognition, assessment and treatment of central sensitization are warranted., (© 2012 European Federation of International Association for the Study of Pain Chapters.)

Objective: The goal of the present study is to systematically review the scientific literature addressing central sensitization and central nociceptive processing in patients with rheumatoid arthritis (RA)., Methods: To identify relevant articles, we searched PubMed and Web of Science. The search strategy was a combination of terms of the following groups: "Rheumatoid arthritis," inflammatory joint pain, or arthritis; AND (central) sensitization, (central) hypersensitivity, central hyperexcitability, pain modulation, pain processing, neural inhibition, or pain physiopathology; AND pain, nociception, hyperalgesia, pain threshold, or algometry. Articles fulfilling the inclusion criteria were screened for methodologic quality with specific checklists to evaluate different study designs (2 independent raters)., Results: Twenty-four full-text articles were included, of which the majority were case-control studies, followed by nonsystematic reviews, cross-sectional studies, and case reports. Methodologic quality was very heterogeneous. Preliminary evidence for generalized hyperalgesia in RA is available. In addition, the mechanism behind impaired central nociceptive processing remains rather obscure. The role of cytokines and neuropeptides especially remains to be elucidated. Windup appears to develop more easily in RA, but evidence in support of impaired nociceptive inhibition and cognitive emotional sensitization (sensitization due to cognitive bias) is scarce., Conclusions: The symmetrical manifestation of the disease, the poor relation between disease activity and symptoms, and the generalized hyperalgesia at both articular and nonarticular sites for different kinds of stimuli are indicative of the presence of central sensitization in RA patients. Further research is required to provide firm evidence in support of various aspects of central sensitization in humans with RA., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Central sensitization provides an evidence-based explanation for many cases of 'unexplained' chronic musculoskeletal pain. Prior to commencing rehabilitation in such cases, it is crucial to change maladaptive illness perceptions, to alter maladaptive pain cognitions and to reconceptualise pain. This can be accomplished by patient education about central sensitization and its role in chronic pain, a strategy known as pain physiology education. Pain physiology education is indicated when: 1) the clinical picture is characterized and dominated by central sensitization; and 2) maladaptive illness perceptions are present. Both are prerequisites for commencing pain physiology education. Face-to-face sessions of pain physiology education, in conjunction with written educational material, are effective for changing pain cognitions and improving health status in patients with various chronic musculoskeletal pain disorders. These include patients with chronic low back pain, chronic whiplash, fibromyalgia and chronic fatigue syndrome. After biopsychosocial assessment pain physiology education comprises of a first face-to-face session explaining basic pain physiology and contrasting acute nociception versus chronic pain (Session 1). Written information about pain physiology should be provided as homework in between session 1 and 2. The second session can be used to correct misunderstandings, and to facilitate the transition from knowledge to adaptive pain coping during daily life. Pain physiology education is a continuous process initiated during the educational sessions and continued within both the active treatment and during the longer term rehabilitation program., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Traditional understanding of osteoarthritis-related pain has recently been challenged in light of evidence supporting a key role of central sensitization in a subgroup of this population. This fact may erroneously lead musculoskeletal therapists to conclude that hands-on interventions have no place in OA management, and that hands-off interventions must be applied exclusively. The aim of this paper is to encourage clinicians in finding an equilibrium between hands-on and hands-off interventions in patients with osteoarthritis-related pain dominated by central sensitization. The theoretical rationale for simultaneous application of manual therapy and pain neuroscience education is presented. Practical problems when combining these interventions are also addressed. Future studies should explore the combined effects of these treatment strategies to examine whether they increase therapeutic outcomes against current approaches for chronic osteoarthritis-related pain. [ABSTRACT FROM AUTHOR]