Jeroen Kregel

Structural and functional brain abnormalities in chronic low back pain: A systematic review ☆

OBJECTIVES The purpose of this systematic review is to analyze the available literature on structural and functional brain abnormalities in chronic low back pain (CLBP) using several brain magnetic resonance imaging (MRI) techniques. METHODS PubMed and Web of Science were systematically screened for relevant literature using different combinations of keywords regarding structural and functional brain imaging techniques in patients with CLBP. Reference lists of included articles were hand-searched for additional literature. Eligible articles were assessed on risk of bias and reviewed by two independent researchers. RESULTS The search query returned 27 articles meeting the inclusion criteria. Methodological quality varied from poor to good. A total of 10 studies evaluated structural gray matter changes. There is conflicting evidence in global gray matter changes, with both increases and decreases shown in different studies. Gray matter changes were demonstrated in specific brain regions. Structural white matter changes were reported in five studies. There is conflicting evidence in total white matter volume due to both increases and unchanged white matter. Several regional differences were identified in which white matter changes were shown. Functional organization during rest was evaluated in 10 studies. CLBP patients showed increased activation in specific regions, together with a disrupted default mode network. A total of six studies evaluated brain activity in response to a nociceptive stimulus. Findings suggest that patients demonstrated increased activity in pain-related regions, and decreased activity in analgesic regions. CONCLUSIONS Overall, there is moderate evidence for regional changes in gray and white matter, together with an altered functional connectivity during rest and increased activity in pain-related areas following painful stimulation, evidencing an upregulated pain matrix. More longitudinal research is needed to clarify the temporal relationship regarding pain and neuroplastic changes, and integration of different brain imaging techniques is warranted.

The Dutch Central Sensitization Inventory (CSI) : factor analysis, discriminative power, and test-retest reliability

Objectives:A standardized assessment of central sensitization can be performed with the Central Sensitization Inventory (CSI), an English questionnaire consisting of 25 items relating to current health symptoms. The aim of this study was to translate the CSI into Dutch, to perform a factor analysis to reveal the underlying structure, examine its discriminative power, and test-retest reliability. Methods:The CSI was first translated into Dutch. A factor analysis was conducted on CSI data of a large group of chronic pain patients (n=368). The ability to discriminate between chronic pain patients (n=188) and pain-free controls (n=49) was determined and the test-retest reliability for chronic pain patients (n=36) and controls (n=45) with a time interval of 3 weeks was evaluated. Results:The exploratory factor analysis resulted in a 4-factor model based on 20 items, representing the domains “General disability and physical symptoms” (Cronbach &agr;=0.80), “Higher central sensitivity”(Cronbach &agr;=0.78), “Urological and dermatological symptoms”(Cronbach &agr;=0.60), and “Emotional distress”(Cronbach &agr;=0.80). Furthermore, a parsimonious second-order factor model was found, where the factor “General central sensitization” was underlying the 4 first-order factors. Chronic pain patients scored significantly worse on all 4 factors. The test-retest reliability was excellent values in both chronic pain patients (ICC=0.88) and controls (ICC=0.91). Discussion:The original CSI was translated into Dutch and did not reveal any problems during data acquisition. The domains represented by the 4 factors may be useful in setting up specific patient profiles and treatment targets. To conclude, the Dutch CSI revealed 4 distinguishable domains, showed good internal consistency for the total score and 3 out of 4 domains, good discriminative power, and excellent test-retest reliability.

Does muscle morphology change in chronic neck pain patients? – A systematic review

BACKGROUND Neck pain is a common disabling worldwide health problem with a high socio-economic burden. Changes underlying the transition to, or the maintenance of a chronic state are still barely understood. Increasing evidence suggests that morphological muscle changes, including changes in cross-sectional area (CSA) or fatty infiltration, play a role in chronic neck pain. However, a structured overview of the current evidence of morphological changes is lacking. OBJECTIVE To systematically review the morphological muscle changes in patients with chronic neck pain, including those with whiplash-associated disorders (WAD) and chronic idiopathic neck pain. STUDY DESIGN & METHODS A systematic review using the PRISMA-guidelines. RESULTS Fourteen of 395 papers were included after extensive screening. Most studies were of moderate methodological quality. A higher CSA was found in all flexor muscles in both patients with WAD and patients with chronic idiopathic neck pain, except for the deeper flexor muscles in patients with chronic idiopathic neck pain. The cervical extensor muscles show an increased CSA at the highest cervical segments in patients with WAD, while most studies in patients with chronic idiopathic neck pain report a decreased CSA in all extensor muscles. Fatty infiltration, which could be accountable for an increased CSA, of both cervical extensors and flexors seems to occur only in patients with WAD. CONCLUSION Some evidence is available for changes in muscle morphology, however more high quality prospective and cross-sectional research is needed to confirm these changes and to identify potential underlying causes that need yet to be discovered.

Brain changes associated with cognitive and emotional factors in chronic pain: A systematic review

An emerging technique in chronic pain research is MRI, which has led to the understanding that chronic pain patients display brain structure and function alterations. Many of these altered brain regions and networks are not just involved in pain processing, but also in other sensory and particularly cognitive tasks. Therefore, the next step is to investigate the relation between brain alterations and pain related cognitive and emotional factors. This review aims at providing an overview of the existing literature on this subject. Pubmed, Web of Science and Embase were searched for original research reports. Twenty eight eligible papers were included, with information on the association of brain alterations with pain catastrophizing, fear‐avoidance, anxiety and depressive symptoms. Methodological quality of eligible papers was checked by two independent researchers. Evidence on the direction of these associations is inconclusive. Pain catastrophizing is related to brain areas involved in pain processing, attention to pain, emotion and motor activity, and to reduced top‐down pain inhibition. In contrast to pain catastrophizing, evidence on anxiety and depressive symptoms shows no clear association with brain characteristics. However, all included cognitive or emotional factors showed significant associations with resting state fMRI data, providing that even at rest the brain reserves a certain activity for these pain‐related factors. Brain changes associated with illness perceptions, pain attention, attitudes and beliefs seem to receive less attention in literature.

Relations Between Brain Alterations and Clinical Pain Measures in Chronic Musculoskeletal Pain: A Systematic Review

UNLABELLED Compelling evidence has shown chronic widespread and exaggerated pain experience in chronic musculoskeletal pain (MSKP) conditions. In addition, neuroimaging research has revealed morphological and functional brain alterations in these patients. It is hypothesized that brain alterations play a role in the persistent pain complaints of patients with chronic MSKP. Nevertheless, lack of overview exists regarding the relations between brain alterations and clinical measures of pain. The present systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, to investigate the relations between structural or functional brain alterations, using magnetic resonance imaging scans, and clinical pain measures in patients with chronic MSKP. PubMed, Web of Science, Cinahl, and Cochrane databases were searched. First, the obtained articles were screened according to title and abstract. Second, the screening was on the basis of full-text. Risk of bias in included studies was investigated according to the modified Newcastle-Ottawa Scale. Twenty studies met the inclusion criteria. Moderate evidence shows that higher pain intensity and pressure pain sensitivity are related to decreased regional gray matter (GM) volume in brain regions encompassing the cingulate cortex, the insula, and the superior frontal and temporal gyrus. Further, some evidence exists that longer disease duration in fibromyalgia is correlated with decreased total GM volume. Yet, inconclusive evidence exists regarding the association of longer disease duration with decreased or increased regional GM volume in other chronic MSKP conditions. Inconclusive evidence was found regarding the direction of the relation of pain intensity and pressure pain sensitivity with microstructural white matter and functional connectivity alterations. In conclusion, preliminary to moderate evidence demonstrates relations between clinical pain measures, and structural and functional connectivity alterations within brain regions involved in somatosensory, affective, and cognitive processing of pain in chronic MSKP. Nevertheless, inconclusive results exist regarding the direction of these relations. Further research is warranted to unravel whether these brain alterations are positively or negatively correlated to clinical pain measures. PERSPECTIVE Structural and functional brain alterations within regions involved in somatosensory, affective, and cognitive pain processing play a crucial role in the persistent pain of chronic MSKP patients. Accordingly, these brain alterations have to be taken into account when assessing and treating patients with chronic MSKP.

Psychological distress and widespread pain contribute to the variance of the central sensitization inventory: A cross-sectional study in patients with chronic pain

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.

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.

Identifying prognostic factors predicting outcome in patients with chronic neck pain after multimodal treatment: A retrospective study

OBJECTIVES This study was conducted to identify possible prognostic factors to predict drop-out and favorable outcome in patients following a multimodal treatment program at an outpatient rehabilitation clinic. METHODS A retrospective cohort study was conducted on 437 patients with chronic neck pain involved in an exercise-based rehabilitation program of an outpatient rehabilitation center between January 2008 and November 2011. Prognostic factors were analyzed through a univariate and a multivariate logistic regression analysis. RESULTS Multivariate logistic regression revealed that a higher age (OR=0.960), presence of headache (OR=0.436) or low back pain (OR=0.525), and having low levels of depression (OR=1.044) increase the odds to complete the multimodal treatment program. A high NDI-score (OR=0.945), a high NRS-score for pain in the upper extremities (OR=0.862), a low NRS score for pain in the neck (OR=1.372), and a trauma in the patients history (OR=0.411) decrease the odds of having a favorable outcome after the given treatment program. CONCLUSION It is important to assess these prognostic factors as they may help therapists to identify patients with a good prognosis or patients at risk. For those at risk, this would allow the treatment approach to be redirected to address their specific needs.

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.

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.