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Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms., Methods: A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software., Results: This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31-.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06-1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18-.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02-.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03-.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [-.47 to -.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = -.79 [-1.27 to -.30]; Z = -3.14; p < .01)., Conclusion: This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Pain is prevalent among children and adolescents. The development and implementation of Pain Neuroscience Education (PNE) strategies tailored to this population remains overlooked in contrast to the adult population., Objective: This study sought to identify the content, delivery methods, and dosage of PNE for children and adolescents available in the literature., Method: We systematically searched PubMed, EMBASE, Physiotherapy Evidence Database, Scopus, Web of Science, Cochrane Library, PsycINFO, and clinical trial registration databases. Inclusion criteria consisted of studies that involved children submitted to a PNE program in community, school, clinics, hospitals or child development centers. We considered studies that included children with and without pain who received PNE strategies associated or not with self-motivational interventions. Studies focusing on psychological interventions were excluded. We extracted data on authors, publication year, country, sample characteristics, health condition, PNE content, study design, context, outcomes, duration, follow-up, main results, dropout, and adverse effects. Data extracted were qualitatively organized., Results: A total of 805 studies were initially reviewed. The final sample comprised 17 studies. Common PNE topics included pain neurophysiology, biopsychosocial influences, pain concepts, self-management, and coping strategies. Delivery methods ranged from slideshows and videos to booklets, with sessions lasting 8-60 min. Schools were the most common setting for these interventions., Conclusion: Our review demonstrates the diversity in PNE content, delivery methods, and intervention dosages among the included studies. Most studies occurred in school settings, potentially limiting its generalizability for clinical contexts., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pain Neuroscience Education (PNE) is a commonly used technique applied by physical therapists in the rehabilitation of chronic pain., Objective: The aim of this study was to culturally adapt an existing PNE for children with chronic pain (PNE4Kids) to Turkish children with chronic pain (PNE4Kids-Turkish)., Methods: A three-round modified Delphi-study was conducted between September 2023 and February 2024. Experts completed questionnaire with 5 items to elicit demographic data and 16 closed and 7 open-ended questions to assess relevance of information, feasibility of stories, visual information, and clarity of message in the 4 main areas of 'normal pain biology', 'pain modulation', 'chronic pain, adaptations, central sensitization', and 'the application and implications of PNE4Kids. MAXQDA software was used for qualitative analysis of open-ended questions. A total of 38 experts (mean age: 36.6 ± 9.05 years, 6 male, 32 female) were recruited for this study., Results: The results of the first round indicated that 84-100 % of Delphi experts strongly agreed or agreed on the relevance of information, feasibility of stories, visual information, and clarity of message in respect of the 4 main areas. During second and third round, an acceptable degree of agreement with clinical usefulness of PNE4Kids-Turkish materials was obtained., Conclusions: PNE4Kids was culturally adapted for Turkish children suffering from chronic pain. The findings of this study mainly highlight the viewpoints of the experts., Implication to Practice: This is the first study to have developed and culturally adapted the PNE4Kids for Turkish children with chronic pain. The PNE4Kids-Turkish is crucial, valuable, helpful, and understandable for Turkish children with chronic pain. In addition, the PNE4Kids-Turkish has the potential to close the gap in research and clinical areas for Turkish children with chronic pain., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Though perioperative pain neuroscience education (PPNE) positively influences patients' surgical outcomes, little is known about the mechanisms behind this treatment's success. Therefore, this study aims to evaluate the potential mediating role of pain cognitions and pain sensitivity in the treatment effect of PPNE on postoperative quality of life in people undergoing surgery for lumbar radiculopathy. This secondary analysis uses data from 120 participants of a randomized controlled trial who were randomized to receive either PPNE or perioperative biomedical education before undergoing surgery for lumbar radiculopathy. Quality of life was assessed 1-year postsurgery using the short form 36-item health survey (SF36) physical and mental component scores. Potential mediators included pain cognitions (ie, kinesiophobia, pain catastrophizing, and hypervigilance) and pain sensitivity (ie, endogenous nociceptive modulation), assessed 6 weeks postsurgery. Mediation models were constructed using structural equation modeling, and 95% confidence intervals (CIs) were calculated using 10,000 bootstrap samples. Analyses show a significant total effect for PPNE (estimate = .464, 95% CI [.105, .825]) and a significant indirect effect via pain catastrophizing on the SF36 physical component (estimate = .124, 95% CI [.001, .293]). No mediating effect was found through the remaining pain cognitions or pain sensitivity measures. Also, no potential mediators were identified for the treatment effect of PPNE on the SF36 mental component. Our findings suggest that pain catastrophizing mediates the treatment effect of PPNE on physical health-related quality of life in people undergoing surgery for lumbar radiculopathy. PERSPECTIVE: This secondary analysis identified pain catastrophizing as a mediator for PPNE in people undergoing surgery for lumbar radiculopathy. More so, its findings indicate that this educational intervention can enhance the postoperative physical health-related quality of life of these patients by addressing their catastrophizing thoughts. TRIAL REGISTRATION: Clinicaltrials.gov (NCT02630732)., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Insomnia is highly prevalent in patients with nonspecific chronic spinal pain (nCSP). Given the close interaction between insomnia and pain, targeting sleep problems during therapy could improve treatment outcomes., Objective: To evaluate the effectiveness of cognitive behavioral therapy for insomnia (CBTi) integrated in best-evidence pain management (BEPM) vs BEPM only in patients with nCSP and insomnia., Design, Setting, and Participants: A multicenter randomized clinical trial with 1-year follow-up was conducted between April 10, 2018, and April 30, 2022. Data and statistical analysis were performed between May 1, 2022, and April 24, 2023. Patients with nCSP and insomnia were evaluated using self-report and at-home polysomnography, to exclude underlying sleep pathologic factors. Participants were treated at the University Hospital Brussels or University Hospital Ghent, Belgium. Intention-to-treat analysis was performed., Interventions: Participants were randomized to either CBTi-BEPM or BEPM only. Both groups received 18 treatment sessions over 14 weeks. The CBTi-BEPM treatment included 6 CBTi sessions and 12 BEPM sessions. The BEPM treatment included pain neuroscience education (3 sessions) and exercise therapy (9 sessions in the CBTi-BEPM group, 15 sessions in the BEPM-only group)., Main Outcomes and Measures: The primary outcome was change in mean pain intensity (assessed with Brief Pain Inventory [BPI]) at 12 months after the intervention. Exploratory secondary outcomes included several pain- and sleep-related outcomes. Blinded outcome assessment took place at baseline, posttreatment, and at 3-, 6-, and 12-month follow-up., Results: A total of 123 patients (mean [SD] age, 40.2 [11.18] years; 84 women [68.3%]) were included in the trial. In 99 participants (80.5%) with 12-month BPI data, the mean pain intensity at 12 months decreased by 1.976 points (reduction of 40%) in the CBTi-BEPM group and 1.006 points (reduction of 24%) points in the BEPM-only group. At 12 months, there was no significant difference in pain intensity change between groups (mean group difference, 0.970 points; 95% CI, -0.051 to 1.992; Cohen d, 2.665). Treatment with CBTi-BEPM resulted in a response for BPI average pain with a number needed to treat (NNT) of 4 observed during 12 months. On a preliminary basis, CBTi-BEPM was, consistently over time and analyses, more effective than BEPM only for improving insomnia severity (Cohen d, 4.319-8.961; NNT for response ranging from 2 to 4, and NNT for remission ranging from 5 to 12), sleep quality (Cohen d, 3.654-6.066), beliefs about sleep (Cohen d, 5.324-6.657), depressive symptoms (Cohen d, 2.935-3.361), and physical fatigue (Cohen d, 2.818-3.770). No serious adverse effects were reported., Conclusions and Relevance: In this randomized clinical trial, adding CBTi to BEPM did not further improve pain intensity reduction for patients with nCSP and comorbid insomnia more than BEPM alone. Yet, as CBTi-BEPM led to significant and clinically important changes in insomnia severity and sleep quality, CBTi integrated in BEPM should be considered in the treatment of patients with nCSP and comorbid insomnia. Further research can investigate the patient characteristics that moderate the response to CBTi-BEPM in terms of pain-related outcomes, as understanding of these moderators may be of utmost clinical importance., Trial Registration: Clinical Trials.gov Identifier: NCT03482856.

OBJECTIVE: To explore whether preoperative pain intensity, pain cognitions, and quantitative sensory measures influence the established effectiveness of perioperative pain neuroscience education (PPNE) on health-related quality of life at 1 year after surgery for lumbar radiculopathy. DESIGN: Secondary analysis of a triple-blinded randomized controlled trial. METHODS: Participants (n = 90) were Dutch-speaking adults (18-65 years) who were scheduled for surgery for lumbar radiculopathy in 3 Belgian hospitals. They were randomized (1:1) to receive PPNE (n = 41) or perioperative biomedical education (n = 49). Linear mixed models were built for health-related quality of life (ie, SF-6D utility values, Physical and Mental Component of the 36-item Short Form Health Survey) using the following independent variables: therapy, time, and preoperative scores for back and leg pain intensity, pain catastrophizing, kinesiophobia, hypervigilance, and quantitative sensory measures. RESULTS: The impact of PPNE on SF-6D utility values over time was influenced by kinesiophobia (F = 3.30, P = .02) and leg pain intensity (F = 3.48, P = .02). Regardless of the intervention, back pain intensity negatively influenced SF-6D values over time (F = 3.99, P = .009). The Physical Component scores were negatively impacted by back pain intensity (F = 9.08, P = .003) and were influenced over time by leg pain intensity (F = 2.87, P = .04). The Mental Component scores were negatively impacted by back pain intensity (F = 6.64, P = .01) and pain catastrophizing (F = 5.42, P = .02), as well as hypervigilance (F = 3.16, P = .03) and leg pain intensity (F = 3.12, P = .03) over time. CONCLUSION: PPNE may be more effective than perioperative biomedical education in improving postoperative health utility values in patients who reported higher kinesiophobia and leg pain intensity before surgery for lumbar radiculopathy. J Orthop Sports Phys Ther 2024;54(4):1-10. Epub 8 January 2024. doi:10.2519/jospt.2024.12051 .

(1) Background : This exploratory study aims to explore the relationship between nonspecific chronic spinal pain (nCSP) and insomnia symptoms, by examining the interconnections, strengths, and directional dependence of the symptoms. In addition, we aim to identify the key symptoms of the nCSP-insomnia relationship and shed light on the bidirectional nature of this relationship. (2) Methods : This study is a secondary analysis of the baseline data (cross-sectional) from a randomized controlled trial, which examined the added value of Cognitive Behavioral Therapy for Insomnia (CBT-I) combined with cognition-targeted exercise therapy, conducted in collaboration with the Universiteit Gent and Vrije Universiteit Brussel (Belgium). One hundred and twenty-three nCSP patients with comorbid insomnia were recruited through the participating hospitals, advertisements, announcements in local newspapers, pharmacies, publications from support groups, and primary care. To explore the interconnections and directionality between symptoms and the strengths of the relationships, we estimated a regularized Gaussian graphical model and a directed acyclic graph. (3) Results : We found only one direct, but weak, link between sleep and pain, namely, between average pain and difficulties maintaining sleep. (4) Conclusions : Despite the lack of strong direct links between sleep and pain, pain and sleep seem to be indirectly linked via anxiety and depression symptoms, acting as presumable mediators in the network of nCSP and comorbid insomnia. Furthermore, feeling slowed down and fatigue emerged as terminal nodes, implying their role as consequences of the network.

Background: Physical exercise is an important element in the rehabilitation of chronic whiplash-associated disorders, with the physiological process underlying pain reduction called exercise-induced hypoalgesia. In chronic whiplash-associated disorders, exercise-induced hypoalgesia appears impaired, and the research suggests a relationship with symptoms of dysfunctional nociceptive processing, such as central sensitization. This study improves our understanding of exercise-induced hypoalgesia in chronic whiplash-associated disorders by examining the differences between the extent of exercise-induced hypoalgesia in subgroups based on scores on the central sensitization inventory (CSI)., Methods: Data were collected from 135 participants with chronic whiplash-associated disorders who completed a set of questionnaires. Pain pressure thresholds and temporal summations were assessed before and after a submaximal aerobic bicycle exercise test., Results: We observed no interaction effect between exercise-induced hypoalgesia and the CSI scores for both pain pressure threshold and temporal summation. No overall statistical effect was measured in the analysis of the effect of time. The pain pressure threshold significantly related to the CSI. The temporal summation showed no correlation., Conclusions: During this study, we did not find evidence for a difference in the presence of exercise-induced hypoalgesia when the subgroups were created based on the central sensitization cluster calculator. Limited evidence was found for the influence of CSI scores on the delta pain pressure threshold.

Background: Chronic spinal pain (CSP) is a major public health problem worldwide, frequently related to sleep problems. Central sensitization (CS) may worsen the clinical picture of CSP patients with insomnia. The aim of this study was to compare self-reported and objectively measured clinical outcomes between insomniac CSP patients with comorbid insomnia with and without symptoms of CS., Methods: A case-control study on baseline self-reported sleep, functioning, and psychological distress through online questionnaires. Objective sleep and physical activity parameters and pressure pain thresholds (PPTs) were assessed through polysomnography, actigraphy, and digital algometry, respectively. Independent sample t-test and Mann-Whitney U tests were used to examine possible differences in the outcome measures between the groups., Results: Data from 123 participants were included and revealed no statistically significant group for objective sleep and physical activity parameters. The CS group, however, presented with worse self-reported sleep (quality sleep, insomnia severity, and dysfunctional beliefs about sleep), increased mental and physical fatigue, and higher psychological distress (anxiety and depressive symptoms), and reported lower PPTs., Conclusions: symptoms of CS may influence perceived sleep and affect functional health and well-being perception but do not seem to affect objective sleep and physical activity.

Background: Perioperative education should be improved to decrease unfavourable outcomes after lumbar surgery. This trial aimed to compare effectiveness in terms of pain, quality of life, pain cognition, surgical experience, healthcare use, work resumption, and cost-effectiveness of perioperative pain neuroscience education (PPNE) vs traditional biomedical education (perioperative biomedical education [PBE]) in people undergoing surgery for lumbar radiculopathy., Methods: In this multicentre RCT (ClinicalTrials.gov: NCT02630732), patients undergoing surgery for lumbar radiculopathy in three Belgian hospitals were randomised to receive PPNE or PBE. Both groups received one preoperative and one postoperative one-to-one education session and a booklet (balanced interventions), with an essentially different content (PPNE: biopsychosocial; PBE: biomedical). Pain was the primary outcome (Visual Analogue Scales+quantitative sensory testing). Assessments were at 3 days, 6 weeks, and 6 and 12 months after surgery., Results: Between March 2016 and April 2020, participants were randomly assigned to PPNE (n=58) or PBE (n=62). At 12 months, PPNE did not lead to significantly better pain outcomes, but it did result in more favourable 36-item Short Form Health Survey physical component (additional increase: 46.94; 95% confidence interval [CI]: 14.16-79.73; medium effect), Tampa Scale of Kinesiophobia (additional decrease: 3.15; 95% CI: 0.25-6.04; small effect), and Pain Catastrophising Scale (additional decrease: 6.18; 95% CI: 1.97-10.39; medium effect) scores. Females of the PPNE group showed higher probability for work resumption (95% vs 60% in the PBE group). PPNE was cost-effective compared with PBE (incremental costs: €-2732; incremental quality-adjusted life years: 0.012)., Conclusions: Perioperative pain neuroscience education showed superior clinical and cost-effectiveness than perioperative biomedical education in people undergoing surgery for lumbar radiculopathy., Clinical Trial Registration: NCT02630732., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Abstract: Sleep disturbances are one of the most frequent reported problems in people with nonspecific chronic spinal pain (nCSP) and presents an additional treatment challenge. Interventions targeting sleep problems are mainly based on subjective sleep complaints and do not take objective sleep into consideration. The aim of this cross-sectional study was to evaluate the relationship and conformity between self-reported and objectively measured sleep parameters (ie, questionnaire vs polysomnography and actigraphy). The baseline data of 123 people with nCSP and comorbid insomnia who are participating in a randomized controlled trial were analyzed. Pearson correlations were used to investigate the relationship between objective and subjective sleep parameters. Differences between objective and subjective sleep parameters were analyzed using t tests. Bland-Altman analyses were performed to quantify and visualize agreement between the different measurement methods. Except for the significant moderate correlation between perceived time in bed (TIB) and actigraphic TIB ( r = 0.667, P < 0.001), all other associations between subjective and objective measures were rather weak ( r < 0.400). Participants underestimated their total sleep time (TST) (mean difference [MD] = -52.37 [-67.94, -36.81], P < 0.001) and overestimated sleep onset latency (SOL) (MD = 13.76 [8.33, 19.20], P < 0.001) in general. The results of this study suggest a discrepancy (differences and lack of agreement) between subjective and objective sleep parameters in people with nCSP and comorbid insomnia. No or weak associations were found between self-reported sleep and objectively measured sleep. Findings suggest that people with nCSP and comorbid insomnia tend to underestimate TST and overestimate SOL. Future studies are necessary to confirm our results., (Copyright © 2023 International Association for the Study of Pain.)

(1) Background: Noradrenaline and serotonin have modulatory roles in pain signaling and in exercise-induced hypoalgesia. Patients with chronic whiplash-associated disorders often show impaired exercise-induced hypoalgesia. Therefore, this study aimed to examine the isolated effect of activating serotonergic or noradrenergic descending pathways on hypoalgesia at rest and in response to exercise in patients with chronic WAD by using respectively a single dose of a selective serotonin reuptake inhibitor (SSRI) and a selective norepinephrine reuptake inhibitor (NRI). (2) Methods: Twenty-five people with chronic WAD participated in this double-blind randomized controlled crossover experiment. Serotonin and noradrenaline concentrations were modulated by the oral ingestion of a single dose of citalopram (i.e., SSRI) or atomoxetine (i.e., SNRI). Quantitative sensory testing (including pressure pain thresholds and conditioned pain modulation) was measured before and after exercise in combination with no medication (1), atomoxetine (2), or citalopram (3) at three different test days. (3) Results: Random-intercept linear mixed models analysis was used to analyze pain outcomes (i.e., pain at rest and exercise-induced hypoalgesia) before and after exercise over the three conditions in patients with chronic WAD. No differences in pain at rest were found between the three conditions before exercise. The effect of exercise on pain outcome measures was not influenced by medication intake. The occupational status of the participants had a significant influence on the effect of exercise and medication on pain outcomes ( p < 0.05). Patients working full-time had some positive effect of atomoxetine on pain facilitation ( p < 0.05). Unemployed patients had some negative effect of citalopram on pain tolerance and experienced exercise-induced hypoalgesia ( p < 0.05). (4) Conclusions: A single dose of citalopram or atomoxetine did not result in changes in hypoalgesia at rest and in response to exercise. These results do not support the use of SSRI or selective NRI to overcome impaired hypoalgesia at rest or in response to exercise in people with chronic WAD. Effect of exercise and medication on pain in patients with chronic WAD is influenced by the occupational status.

Background: Pain is a major symptom in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the underlying mechanism causing generalized pain in children with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome is unclear, central sensitization has been suggested as a possible explanation. The aim of this study was to explore the feasibility of a study protocol for a future case-control study, investigating features of central sensitization in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome., Methods: Central sensitization features were measured in ten patients and nine healthy controls aged 13-17 years via experimental pain measurement quantifying primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia. Descriptive statistics were used. Frequency, median, and range values were calculated., Results: Eleven out of 57 patients chose to participate. No control could be recruited through public schools. Therefore, a convenience sampling strategy was used for the recruitment of the control group. The process of assessing primary and secondary hyperalgesia, endogenous pain modulation, and exercise-induced hyperalgesia was well tolerated by all participants (patients and controls). When assessing endogenous pain modulation via conditioned pain modulation, two participants in the patient group and three in the control group did not achieve a pain experience ≥ 3 on the numerical rating scale when immersing their hands in cold water., Conclusion: This study investigated the feasibility, safety, and toleration of experimental pain measurements in adolescents with hypermobility spectrum disorder or hypermobile Ehlers-Danlos syndrome. Although the test protocol proved to be sufficiently feasible for use with the participant group, it will need to be adapted in the main study in order to obtain more reliable data. Recruitment, especially of participants for the control group, can be a major obstacle for future studies and requires careful planning., Trial Registration: Researchweb.org, 270,501. Registered on 9 May 2019., (© 2023. The Author(s).)

(1) Background: Dysregulation in serotonergic and noradrenergic systems may be implicated in the neurobiophysiological mechanisms underlying pain-related cognitive impairment in chronic whiplash-associated disorders (CWAD). This study aimed to unravel the role of serotonergic and noradrenergic descending pathways in cognitive functioning at rest and in response to exercise in people with CWAD. (2) Methods: 25 people with CWAD were included in this double-blind, randomized, controlled crossover study. Endogenous descending serotonergic and noradrenergic inhibitory mechanisms were modulated by using a single dose of a selective serotonin reuptake inhibitor (Citalopram) or a selective norepinephrine reuptake inhibitor (Atomoxetine). Cognitive performance was studied at rest and in response to exercise (1) without medication intake; (2) after intake of Citalopram; and (3) after intake of Atomoxetine. (3) Results: After Atomoxetine intake, selective attention improved compared with the no medication day ( p < 0.05). In contrast, a single dose of Citalopram had no significant effect on cognitive functioning at rest. When performing pairwise comparisons, improvements in selective attention were found after exercise for the no medication condition ( p < 0.05). In contrast, after intake of Citalopram or Atomoxetine, selective and sustained attention worsened after exercise. (4) Conclusions: A single dose of Atomoxetine improved selective attention only in one Stroop condition, and a single dose of Citalopram had no effect on cognitive functioning at rest in people with CWAD. Only without medication intake did selective attention improve in response to exercise, whereas both centrally acting medications worsened cognitive performance in response to a submaximal aerobic exercise bout in people with CWAD.

Objective: The present cross-sectional study aims to unravel associations of pain intensity and cognitions with quantitative sensory testing in people scheduled for surgery for lumbar radiculopathy. Additionally, insight will be provided into the presence of dysfunctional nociceptive processing and maladaptive pain cognitions in this population., Design: Cross-sectional study., Setting: Data from three hospitals in Belgium., Subjects: The final sample comprised 120 participants with lumbar radiculopathy scheduled for surgery, included between March 2016 and April 2019., Methods: Self-reported pain intensity was assessed on a visual analog scale, and pain cognitions were assessed with self-reported questionnaires (Pain Catastrophizing Scale, Tampa Scale for Kinesiophobia, and Pain Vigilance and Awareness Questionnaire). Quantitative sensory testing (detection thresholds, pain thresholds, temporal summation, and conditioned pain modulation) was evaluated, as well., Results: Evidence was found for the presence of an impaired inhibitory response to nociceptive stimuli and maladaptive pain cognitions in this population. Kinesiophobia was found to be present to a maladaptive degree in the majority of the patients (n = 106 [88%]). Significant, but weak, associations between electrical pain thresholds at the sural nerves and leg pain intensity (sural nerve symptomatic side: r = -0.23; P = 0.01; non-symptomatic side: r = -0.22; P = 0.02) and kinesiophobia levels (sural nerve non-symptomatic side: r = -0.26; P = 0.006) were identified., Conclusions: Electrical detection thresholds and correlates for endogenous nociceptive facilitation and inhibition were not found to be related to any of the pain cognitions or to pain intensity in people scheduled to undergo surgery for lumbar radiculopathy., (© The Author(s) 2022. 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.)

This cross-sectional study explored associations between demographics, pain intensity and cognitions on the one hand and healthcare use (HCU) on the other hand in people undergoing surgery for lumbar radiculopathy. HCU during the 2 months preceding surgery was evaluated using a retrospective questionnaire. Demographics included sex, age and level of education and equivalent income. Back and leg pain intensity were evaluated using a visual analogue scale. Pain cognitions were assessed with the Tampa scale of kinesiophobia, the pain catastrophizing scale and the pain vigilance and awareness questionnaire. The sample comprised 120 participants (52% males; 49 years (Quartile (Q)1-Q3: 37.3-57.43)). The number of visits to the general practitioner was associated with sex (incidence rate ratio (IRR) for males = 0.811; p = 0.050), pain catastrophizing (IRR = 1.010; p = 0.041), pain magnification (IRR = 1.058; p = 0.004) and leg pain intensity (IRR = 1.004; p = 0.038). The number of neurosurgeon visits was associated with level of education (IRR moderate education = 1.518; p = 0.016 (reference: low education)). Receiving zero physiotherapy visits was associated with higher back pain intensity (Beta = 0.018; p = 0.028). Highest level of analgesics used was associated with sex (IRR for males = 0.502; p = 0.047) and leg pain (IRR = 1.014; p = 0.034). Only the association between general practitioner visits and pain magnification remained significant in multivariable analyses (IRR = 1.061; p = 0.033). The results suggest a rather indirect relationship between HCU and demographics, pain intensity and cognitions, involving a potential interplay between several patient- and healthcare system-related factors.

The current study evaluated the feasibility and preliminary clinical impact of robot-led distraction during needle procedures in children with chronic diseases on pain-related memories. Participants were 22 children (8−12 years old) diagnosed with a chronic disease (e.g., chronic immune deficiency) and undergoing a needle procedure as part of their routine treatment. Children were randomized to the experimental group (i.e., robot-led distraction) or control group (i.e., usual care). For feasibility, we evaluated study- and needle-procedure-related characteristics, intervention fidelity and acceptability, and nurse perceptions of the intervention. Primary clinical outcomes included children’s memory bias for pain intensity and pain-related fear (1 week later). Results indicated that intervention components were >90% successful. Overall, the robot-led distraction intervention was perceived highly acceptable by the children, while nurse perceptions were mixed, indicating several challenges regarding the intervention. Preliminary between-group analyses indicated a medium effect size on memory bias for pain intensity (Hedges’ g = 0.70), but only a very small effect size on memory bias for pain-related fear (Hedges’ g = 0.09), in favor of the robot-led distraction intervention. To summarize, while feasible, certain challenges remain to clinically implement robot-led distraction during needle procedures. Further development of the intervention while accounting for individual child preferences is recommended.

Pain affects everyone hence one can argue that it is in each individual's interest to understand pain in order to hold correct and adaptive beliefs and attitudes about pain. In addition, chronic pain is reaching pandemic proportions and it is now well known that people living with chronic pain have a reduced life expectancy. To address and to prevent the growth of this public health disaster, we must start looking beyond adulthood. How children view pain has an impact on their behavioral coping responses which in turn predict persistent pain early in the lifespan. In addition, children who suffer from chronic pain and who are not (properly) treated for it before adolescence have an increased risk of having chronic pain during their adult life. Explaining pain to children and youth may have a tremendous impact not only on the individual child suffering from chronic pain but also on society, since the key to stop the pain pandemic may well lie in the first two decades of life. In order to facilitate the acquisition of adaptive behavioral coping responses, pain education aims to shift people's view on pain from being an apparent threat towards being a compelling perceptual experience generated by the brain that will only arise whenever the conceivable proof of danger to the body is greater than the conceivable proof of safety to the body. Nowadays a lot of pain education material is available for adults, but it is not adapted to children's developmental stage and therefore little or not suitable for them. An overview of the state-of-the-art pain education material for children and youth is provided here, along with its current and future areas of application as well as challenges to its development and delivery. Research on pediatric pain education is still in its infancy and many questions remain to be answered within this emerging field of investigation., (© 2022. The Author(s).)

Background: In healthy people and people with nonspecific chronic spinal pain (nCSP) and/or insomnia, participation in physical activity on a regular basis has several physical and psychological health benefits. However, people with chronic conditions often tend to reduce physical activity participation which can lead to deconditioning over time. Currently, there are no known predictors for an (in)active lifestyle (before and after physical therapy treatment) in people with chronic spinal pain and comorbid insomnia., Objective: To examine predictors of pre-treatment moderate-to-vigorous physical activity (MVPA) and to examine determinants for a change in MVPA in response to 14-weeks of active physical therapy treatment in people with nonspecific chronic spinal pain (nCSP) and comorbid insomnia., Methods: Baseline data and post-treatment data were analyzed for 66 participants. A linear multiple regression analysis was conducted to examine which factors predict MVPA at baseline. Linear mixed-effects modeling was used to identify determinants for change in MVPA in response to an active physical therapy treatment., Results: Physical fatigue (b = -0.9; 95%CI: -1.59, -0.15), less limitations in functioning as a result of emotional problems (b = 0.1; 95%CI: 0.03, 0.10), mental fatigue (b = -1.0; 95%CI: -1.67, -0.43), lower general sleep quality (b= 0.7; 95%CI: 0.22, 1.17), and body mass index (b = -0.5; 95%CI: -0.93, -0.16) were significant predictors of baseline MVPA. The regression model explained 33.3% of the total variance in baseline MVPA. The change of MVPA in response to the treatment ranged from a decrease of 17.5 to an increase of 16.6 hours per week. No determinants for change in MVPA after treatment could be identified., Conclusion: People with nCSP and comorbid insomnia are more likely to engage in MVPA if they report, at baseline, lower sleep quality, fewer limitations in functioning resulting from emotional problems, lower body mass index, as well as less physical and mental fatigue., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM). We aimed to determine the interactions between genetic and epigenetic mechanisms regulating COMT and its influence on inflammatory markers and symptoms in patients with CFS/FM., Methods: A case-control study with repeated-measures design was used to reduce the chance of false positive and increase the power of our findings. Fifty-four participants (28 patients with CFS/FM and 26 controls) were assessed twice within 4 days. The assessment included clinical questionnaires, neurophysiological assessment (pain thresholds, temporal summation, and conditioned pain modulation), and blood withdrawal in order to assess rs4818, rs4633, and rs4680 COMT polymorphisms and perform haplotype estimation, DNA methylation in the COMT gene (both MB-COMT and S-COMT promoters), and cytokine expression (TNF-α, IFN-γ, IL-6, and TGF-β)., Results: COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-β expression, and symptoms. However, this was not specific for one condition. Significant between-group differences were found for increased DNA methylation in the MB-COMT promoter and decreased IFN-γ expression in patients., Discussion: Our results are consistent with basic and clinical research, providing interesting insights into genetic-epigenetic regulatory mechanisms. MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted. We recommend future research to employ a repeated-measure design to control for biomarkers variability and within-subject changes., (© 2022. The Author(s).)

Objectives: Early memories of pain contribute to fear and may underlie the maintenance and development of chronic pain into adulthood. Accordingly, understanding determinants that may impact children's pain memory development is key. This study examined (a) the effect of a brief engaging pain educational video in healthy children before undergoing an experimental pain task upon children's recalled pain intensity and pain-related fear and (b) the moderating role of parental pain- and non-pain-attending verbalizations before and after the pain task., Methods: Seventy-seven children (8-15 years old) participated in an experimental heat pain task, including actual heat pain stimuli delivered through a thermode on their forearm. Children were randomized to the experimental group (i.e., watching a pain educational video) or the control group (i.e., no video). Children's recalled pain intensity and pain-related fear were elicited 2 weeks later., Results: Findings showed that recalled pain intensity (but not recalled pain-related fear) of children who watched the pain educational video was significantly lower compared to the control group (p = .028). Further, parental pain-attending verbalizations before the pain task moderated the impact of the video upon children's recalled pain intensity (p = .038). Specifically, children in the control group, but not the experimental group, whose parents used less pain-attending verbalizations recalled higher pain intensity, whereas children whose parents used more pain-attending verbalizations recalled lower pain intensity., Conclusions: As children's pain memories have important implications for pain assessment, treatment, and health across the lifespan, these findings might have important implications for the prevention of development or maintenance of maladaptive pain-related outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Most people who have nonspecific chronic spinal pain (nCSP) report comorbid insomnia. However, in current treatment strategies for nCSP, insomnia is usually not addressed. Considering the bidirectional interaction between pain and sleep and its underlying psychophysiological mechanisms, insomnia may increase the risk of developing adverse physical and psychological health outcomes and should thus no longer be left untreated. As suggested by previous pilot studies, adding cognitive behavioral therapy for insomnia to the contemporary evidence-based biopsychosocial physical therapy approach may also improve pain outcomes in nCSP. This manuscript aims to provide practical guidelines on hybrid physical therapy, including the combination of the following components: (1) pain neuroscience education (eg, to reconceptualize pain) and cognition-targeted exercise therapy (eg, graded exposure to functional daily life movements), and (2) cognitive behavioral therapy for insomnia (sleep psychoeducation, behavioral and cognitive therapy, correction of sleep hygiene, and relaxation therapy) can be deployed for the management of patients who have chronic spinal pain. Impact. Due to the major impact sleep disturbances have on pain and disability, insomnia as a comorbidity should no longer be ignored when treating patients with chronic spinal pain., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Quantitative Sensory Testing (QST) is used to test somatosensory functioning in on people with chronic LBP in secondary/tertiary health care facilities. Studies using QST-testing on LBP populations in primary care are scarce. Central Sensitization Inventory (CSI) measures central sensitization (CS)-related symptoms and studies investigating the differences between QST-testing and participants with LBP with a positive and negative score on the CSI questionnaire are also rare. This case-control study investigates differences of an extensive QST-measurement between patients with acute, chronic LBP, and pain-free controls (PFCs) in primary care. Secondary aim is to investigate differences of an extensive QST-measurement between "CS" and "no-CS" group., Materials and Methods: Participants with LBP were recruited from November 2016 to October 2019. Demographic and clinical information was collected and a standardized QST protocol was taken. Data analysis involved determining differences between groups., Results: Data of 100 participants with LBP and 50 PFCs were analyzed. Heat pain thresholds, pressure pain threshold, and conditioned pain modulation local and remote were significantly moderately to relatively strongly affected by acute, chronic LBP and PFCs (P<0.001 to 0.001). Lumbar temporal summation was significantly moderately affected by acute, chronic LBP, and PFCs (P=0.001). Only pressure pain threshold showed significant difference between "CS" and "no-CS" group (P=0.001 to 0.002)., Discussion: Signs of enhanced nociceptive processing and disturbed top-down nociceptive modulation are apparent in people with acute and chronic LBP in primary care. Results indicate existence of central mechanisms in LBP in primary care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Whether parental presence during their children's painful medical procedures is advantageous with regard to children's pain-related outcomes is questionable. Research on this topic is equivocal, and additional questions, such as whether levels of parental involvement may play a role as well, remain to be addressed. The purpose of this systematic review is to summarize and critically appraise the literature on the impact of parental presence vs absence during their children's painful medical procedures on the child's pain-related outcomes., Methods: The review protocol was registered on Prospero (ID CRD42018116614). A systematic search in PubMed, Web of Science, and PsycArticles resulted in 22 eligible studies incorporating 2,157 participants. Studies were considered eligible if they included children (≤18 years old) undergoing a painful medical procedure and compared parental presence and/or involvement with parental absence during the procedure., Results: The children's pain-related outcomes included self-reported pain intensity, self-reported fear, anxiety and distress, observed pain-related behavior, and physiological parameters. Overall, evidence points in the direction of beneficial effects of parental presence vs absence with regard to children's self-reported pain intensity and physiological parameters, whereas mixed findings were recorded for children's self-reported fears, anxiety and distress, and observed pain-related behaviors., Conclusions: To provide clear recommendations on how to involve the parent during the procedure, as well as for which type of children and parents parental presence has the best effects, further research is needed, as indicated in this review., (© The Author(s) 2021. 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.)

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

Sleep is interrelated with the experience of chronic pain and represents a modifiable lifestyle factor that may play an important role in the treatment of children and adolescents with chronic pain. This is a topical review of assessment and treatment approaches to promote sleep health in children and adolescents with chronic pain, which summarizes: relevant and recent systematic reviews, meta-analyses, and methodologically sound prospective studies and clinical trials. Recommendations are provided for best practices in the clinical assessment and treatment of sleep health in youth with chronic pain. This overview can also provide researchers with foundational knowledge to build upon the best evidence for future prospective studies, assessment and intervention development, and novel clinical trials.

Purpose: The primary goal of this study was to compare the health-related quality of life (HRQoL) of people with lumbar radiculopathy to age- and sex-adjusted population norms. Additionally, it aimed to explore the associations between the HRQoL difference scores and measures related to pain cognitions, pain intensity, and endogenous nociceptive modulation., Methods: Using answers from the Short Form 36-item Health Survey and UK population norms, SF-6D difference scores were calculated. A one-sample t test was used to assess the SF-6D difference scores. Univariate and multivariate regression analyses were used to assess the associations between SF-6D difference scores and pain intensity [Visual Analogue Scale (VAS) for back and leg pain], pain cognitions [Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia (TSK), Pain Vigilance and Awareness Questionnaire (PVAQ)], and correlates for endogenous nociceptive modulation using quantitative sensory testing., Results: One hundred and twenty people with lumbar radiculopathy scheduled for surgery were included in this study. The mean SF-6D difference score of - 0.26 [SD = 0.09] was found to be significantly less than 0 [95%CI: - 0.27 to - 0.24]. Univariate analyses showed a significant influence from PCS, TSK, and PVAQ on the SF-6D difference scores. The final multivariate regression model included PCS and PVAQ, with only PCS maintaining a statistically significant regression coefficient [b = - 0.002; 95% CI: - 0.004 to - 0.001]., Conclusion: People diagnosed with lumbar radiculopathy report significantly lower HRQoL scores when compared with age- and sex-adjusted UK norm values. Even though all examined pain cognitions were found to have a significant association, pain catastrophizing showed the most significant relation to the SF-6D difference scores., Clinical Trial Registration: ClinicalTrials.gov Identifier No. NCT02630732. Date of registration: November 25, 2015., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Pain education resources for children using appropriate language and illustrations remain scarce., Objectives: We aimed to summarize the development process and testing for face and content validity of a structured comic book about pain education for children., Methods: A first draft of a comic book was developed (Portuguese and English) based on pain education concepts. Experts in pediatric pain from different countries analyzed content, objectives, language, illustrations, layout, motivation, and cultural adjustment. A third draft developed in Portuguese considering experts' suggestions was presented to children and parents in Brazil. The total adequacy score was calculated from the sum of the scores obtained in each domain, divided by the maximum total score. Descriptive analysis is presented., Results: The expert panel was composed of 11 (64.7%) physical therapists, and 6 (35.3%) psychologists. The total adequacy score (0-100%) was 87.74%. The third draft version of the comic book was presented to 28 children and the final version was presented to 16 children with a mean age of 9.6 years. Children were totally satisfied (n=4; 26.7%) or satisfied (n=9; 56.2%) with the story of the comic book. The readability of the comic book was considered suitable for grades 4 to 6 educational level., Conclusion: The comic book "A Journey to Learn about Pain" was validated for face and content validity by the expert panel and the Brazilian target population. This comic book is available in Portuguese and English and can be a potentially useful resource for children., (Copyright © 2021 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Chronic whiplash associated disorders (CWAD) are characterized by long-lasting symptoms of neck pain occurring after an acceleration-deceleration injury. Central sensitization (CS) has been suggested as the possible underlying mechanism for these symptoms, and is characterized by changes in the central nervous system. Besides CS, psychological factors are believed to play an important role in the experience of (chronic) pain., Objective: Investigating the relationships between self-reported pain, disability, quality of life, psychological factors, and symptoms of CS; and electrical-based quantitative sensory testing (QST) outcomes in CWAD patients. Secondly, to investigate the differences in QST between CWAD patients and pain-free controls., Methods: Seventy-two individuals with CWAD and 55 pain-free controls underwent electrical stimuli-based QST. Detection and pain thresholds (EPT), temporal summation (TS), and conditioned pain modulation were examined. Spearman correlation and linear mixed models analyses were performed to assess, respectively, the hypothesized associations and group differences in QST., Results: The Pain Catastrophizing magnification subscale correlated with the left wrist EPT (r=-0.332; P=0.004), and the Pain Anxiety Symptom Scale-20 with the left wrist (r=-0.325; P=0.005) and ankle (r=-0.330; P=0.005) EPT. TS at the ankle correlated with the CS inventory (r=0.303; P=0.010), Short Form 36 pain subscale (r=-0.325; P=0.005), and Illness Perception Questionnaire revised consequences subscale (r=0.325; P=0.005). EPTs left (P=0.011) and right wrist (P=0.023) were lower in the CWAD group, but conditioned pain modulation and TS did not differ between groups., Conclusion: QST outcomes relate to psychological constructs, rather than to self-reported pain intensity and distribution. Local hyperalgesia was found in individuals with CWAD, but no differences in endogenous pain facilitation nor inhibition., Competing Interests: D.L. was funded by the Bijzonder Onderzoeksfonds (BOF) Gent, Belgium. I.C., W.W., and A.M.: were funded by the Flemish Research Institution (FWO), Brussels, Belgium. The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pain neuroscience education (PNE) has received increasing research attention demonstrating beneficial effects on pain-related outcomes in adults. Conversely, studies on the effectiveness of PNE in children are scarce., Methods: This study investigated the effect of a pain educational video intervention on child pain-related outcomes (i.e. experienced pain intensity, pain-related fear and catastrophic worry about pain, pain threshold and pain knowledge) in healthy children undergoing an experimental pain task. Furthermore, the moderating role of children's demographic (i.e. sex and age) and psychological (i.e. baseline pain knowledge and anticipated pain intensity, pain-related fear and catastrophic worry) characteristics was examined. Participants were 89 children (M age  = 11.85, SD = 1.78), randomly assigned to either a condition whereby they were instructed to watch a brief pain educational video (i.e. experimental group) or to a control condition whereby they did not watch any video., Results: Study findings revealed that accurate pain knowledge and pain threshold were higher amongst children in the experimental group compared to the control group. In contrast with expectations, no main effects of the video intervention were observed for experienced pain intensity, pain-related fear and catastrophic worry. Moderation analyses indicated that the video intervention contributed, in comparison with the control condition, to higher levels of pain knowledge amongst younger children only and to higher pain thresholds amongst boys only., Conclusions: Further investigation is needed to optimize pain educational video interventions and to determine whether more beneficial outcomes can be found in clinical (i.e. non-experimental) situations and in children with persistent or recurring pain problems., Significance: Examining the impact of pain educational interventions within a non-clinical setting is deemed particularly important given that adaptive pain coping strategies likely play an important role in preventing the development and maintenance of future maladaptive pain-related behaviour. Further, study findings provide preliminary evidence of baseline and demographic (i.e. age and sex) characteristics explaining differences in the effect of a pain educational video intervention in pain knowledge and pain-related experiences during experimental pain., (© 2021 European Pain Federation - EFIC®.)

Chronic spinal pain, including both neck and low back pain, is a common disabling disorder in which sleep problems are frequently reported as a comorbidity. The complex processes of both sleep and chronic pain seem to have overlapping mechanisms, which may explain their often established bidirectional relationship. This systematic review aims to investigate the assumed association between sleep and chronic spinal pain by providing an overview of the literature from the last decade. Eligible studies were obtained by searching four databases (PubMed, Embase, Web of Science, and PsycARTICLES). Articles were found relevant if they included a human adult population and investigated the possible association between sleep parameters and chronic spinal pain. Only studies published after January 2009 were included, as this review aimed to provide an update of a previous literature overview on this topic. The quality of the studies was assessed by risk of bias and level of evidence. A total of twenty-seven studies (6 cohort, 5 case-control, and 16 cross-sectional studies) were included in this systematic review. The methodological quality of these studies was low to moderate. The majority of studies reported weak to moderate evidence for an association between sleep parameters and chronic spinal pain, with more severe pain accompanied by more disturbed sleep. Addressing frequently reported sleep problems in chronic spinal pain patients therefore appears to be a necessary complement to pain management to achieve optimal treatment outcomes.

Insomnia is a major problem in the chronic spinal pain (CSP) population and has a negative impact on health and well-being. While insomnia is commonly reported, underlying mechanisms explaining the relation between sleep and pain are still not fully understood. Additionally, no reviews regarding the prevention of insomnia and/or associated factors in people with CSP are currently available. To gain a better understanding of the occurrence of insomnia and associated factors in this population, we conducted a systematic review of the literature exploring associates for insomnia in people with CSP in PubMed, Web of Science and Embase. Three independent reviewers extracted the data and performed the quality assessment. A meta-analysis was conducted for every potential associate presented in at least two studies. A total of 13 studies were found eligible, which together identified 25 different potential associates of insomnia in 24,817 people with CSP. Twelve studies had a cross-sectional design. Moderate-quality evidence showed a significantly higher rate for insomnia when one of the following factors was present: high pain intensity, anxiety and depression. Low-quality evidence showed increased odds for insomnia when one of the following factors was present: female sex, performing no professional activities and physical/musculoskeletal comorbidities. Higher healthcare use was also significantly related to the presence of insomnia. One study showed a strong association between high levels of pain catastrophizing and insomnia in people with chronic neck pain. Last, reduced odds for insomnia were found in physically active people with chronic low back pain compared to inactive people with chronic low back pain. This review provides an overview of the available literature regarding potential associates of insomnia in people with CSP. Several significant associates of insomnia were identified. These findings can be helpful to gain a better understanding of the characteristics and potential origin of insomnia in people witch CSP, to identify people with CSP who are (less) likely to have insomnia and to determine directions of future research in this area.

Pediatric chronic pain is a challenging problem for children and their families, although it is still under-recognized and under-treated. The aim of this study was to investigate whether a pain neuroscience education program for children (PNE4Kids) delivered to healthy children aged 8 to 12 years old and attended by their parents would result in improved parental knowledge about pain neurophysiology, decreased parental pain catastrophizing about their own pain and their children's, decreased parental pain vigilance and awareness, and decreased fear of pain in children. Twenty-seven healthy child-parent dyads received a 45 min PNE4Kids session. Demographic data were collected, and the Neurophysiology of Pain Questionnaire (NPQ), Fear of Pain Questionnaire-Parent Proxy Report (FOPQ-P), Pain Catastrophizing Scale (PCS), Pain Catastrophizing Scale for Parents (PCS-P), and the Pain Vigilance and Awareness Questionnaire (PVAQ) were completed by the parents before and after the PNE4Kids session. Twenty-six dyads completed study participation. In response to the PNE4Kids session, significant short-term (1 week) improvements were shown in the NPQ ( p < 0.001) and the FOPQ-P ( p = 0.002). Parents' level of pain knowledge and children's fear of pain, reported by their parents, improved after a 45 min PNE4Kids session. Thus, PNE4Kids should likewise be further investigated in healthy child-parent dyads as it might be useful to target parental and children's pain cognitions at a young age.

Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain phenotypes., Competing Interests: Declaration of interests EK reports personal fees from Eli Lilly and personal fees from Lundbeck, outside the submitted work. DC reports grants and personal fees from Aptinyx, Eli Lilly, Samumed, Tonix, Nix Patterson on behalf of State of OK, and Lundbeck Pharmaceuticals, and Pfizer, outside the submitted work. JN and the Vrije Universiteit Brussel received lecturing and teaching fees from various professional associations and educational organisations. SG reports grants from NIH, and personal fees from Rehab Essentials and Med Risk, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.)

Objectives: Literature has demonstrated inconsistent findings regarding the impact of parental responses on child pain-related outcomes. Yet, research into factors that may underlie inconsistent findings regarding the variable impact of parental responses is lacking. The current study investigated the moderating role of parental distress in understanding the impact of parental pain-attending (eg, reassuring the child) and non-pain-attending (eg, distracting the child with humor) responses on child pain behavior (eg, crying)., Methods: Children (18 y and younger) with leukemia, undergoing a lumbar puncture (LP) and/or bone marrow aspiration procedure, and one of their parents, were recruited from the Pediatric Ghent University Hospital. Parent-child interactions were videotaped after the procedure allowing coding of parental responses and child pain behavior. Parents self-reported on experienced personal distress., Results: Participants consisted of 42 children (24 boys, 18 girls) with leukemia and one of their parents. Children were 0.6 to 15 (7.08±4.39) years old. Findings indicated a positive association between parental pain-attending and child pain behavior, but only when parents reported high levels of distress (β=0.56, P=0.001). No association was observed for parents reporting low levels of distress (β=-0.09, ns). Parental non-pain-attending responses contributed to lower child pain behavior (β=-0.24, P=0.045), independently of parental distress (β=-0.07, ns)., Discussion: The current findings point to the moderating role of parental distress in understanding the impact of parental responses on child pain behavior and highlight the importance of interventions targeting parental emotion regulation to promote optimal child pain outcomes., Competing Interests: Grant support for E.R. was provided by a Chair funded by the Berekuyl Academy/European College for Decongestive Lymphatic Therapy, the Netherlands and awarded to the Vrije Universiteit Brussel, Belgium. K.I. is a postdoctoral research fellow, partly funded by the Research Foundation—Flanders (FWO), Brussels, Belgium. L.C. was funded by the Research Foundation—Flanders (FWO), Brussels, Belgium. None of these sponsors played a role in the (1) study design, (2) collection, analysis and interpretation of data, (3) writing of the report, or (4) in the decision to submit the paper for publication. The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Central sensitization is present in different pain conditions, including chronic whiplash-associated disorders. In the absence of a gold standard method of assessment to determine the presence of central sensitization, quantitative sensory testing is currently understood as an optimal proxy. Laboratory sensory testing is, however, not feasible in clinical practice, and the Central Sensitization Inventory was developed as an alternative. The aim of the current study was to evaluate the convergent validity of the Central Sensitization Inventory in chronic whiplash-associated patients by determining the association between the Central Sensitization Inventory and quantitative sensory testing, pain intensity, fatigue, and psychosocial factors., Methods: A total of 125 chronic whiplash-associated patients completed multiple questionnaires and were subjected to pressure pain thresholds and temporal summation., Results: . The Central Sensitization Inventory showed a strong association with constructs of general psychopathology, anxiety, distress, depression, and somatization in chronic whiplash-associated disorders. Moderate correlations were found with fatigue and intrusive and avoidant phenomena after a variety of traumatic events. No significant association was found between the Central Sensitization Inventory and pressure pain thresholds and temporal summation, nor between the Central Sensitization Inventory and other pain measurements., Conclusions: Overall, we found that the Central Sensitization Inventory is better in identifying the psychosocial factors related to central sensitization in chronic whiplash-associated disorders than the central nervous system adaptations. Thus, the convergent validity of the Central Sensitization Inventory appears to be only partially present in chronic whiplash-associated disorders., (© 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.)

Background: With its high temporal resolution, electroencephalography (EEG), a technique that records electrical activity of cortical neuronal cells, is a potentially suitable technique to investigate human somatosensory processing. By using EEG, the processing of (nociceptive) stimuli can be investigated, along with the functionality of the nociceptive pathway. Therefore, it can be applied in chronic pain patients to objectify whether changes have occurred in nociceptive processing. Typically, so-called event-related potential (ERP) recordings are used, where EEG signals are recorded in response to specific stimuli and characterized by latency and amplitude., Objective: To summarize whether differences in somatosensory processing occur between chronic pain patients and healthy controls, measured with ERPs, and determine whether this response is related to the subjective pain intensity., Design: Systematic review., Setting and Methods: PubMed, Web of Science, and Embase were consulted, and 18 case-control studies were finally included., Subjects: The chronic pain patients suffered from tension-type headache, back pain, migraine, fibromyalgia, carpal tunnel syndrome, prostatitis, or complex regional pain syndrome., Results: Chronic neuropathic pain patients showed increased latencies of the N2 and P2 components, along with a decreased amplitude of the N2-P2 complex, which was also obtained in FM patients with small fiber dysfunction. The latter also showed a decreased amplitude of the N2-P3 and N1-P1 complex. For the other chronic pain patients, the latencies and the amplitudes of the ERP components did not seem to differ from healthy controls. One paper indicated that the N2-P3 peak-to-peak amplitude correlates with the subjective experience of the stimulus., Conclusions: Differences in ERPs with healthy controls can mostly be found in chronic pain populations that suffer from neuropathic pain or where fiber dysfunction is present. In chronic pain populations with other etiological mechanisms, limited differences were found or agreed upon across studies., (© 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.)

Oxidative stress can be induced by various stimuli and altered in certain conditions, including exercise and pain. Although many studies have investigated oxidative stress in relation to either exercise or pain, the literature presents conflicting results. Therefore, this review critically discusses existing literature about this topic, aiming to provide a clear overview of known interactions between oxidative stress, exercise, and pain in healthy people as well as in people with chronic pain, and to highlight possible confounding factors to keep in mind when reflecting on these interactions. In addition, autonomic regulation and epigenetic mechanisms are proposed as potential mechanisms of action underlying the interplay between oxidative stress, exercise, and pain. This review highlights that the relation between oxidative stress, exercise, and pain is poorly understood and not straightforward, as it is dependent on the characteristics of exercise, but also on which population is investigated. To be able to compare studies on this topic, strict guidelines should be developed to limit the effect of several confounding factors. This way, the true interplay between oxidative stress, exercise, and pain, and the underlying mechanisms of action can be revealed and validated via independent studies.

Objective: The epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study was undertaken to explore the role of brain-derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM)., Methods: A repeated-measures study was conducted in 54 participants (28 patients with CFS/FM and 26 matched healthy controls). Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. Serum BDNF (sBDNF) protein levels were measured using enzyme-linked immunosorbent assay, while polymorphism and DNA methylation were measured in blood using pyrosequencing technology. To assess the temporal stability of the measures, participants underwent the same assessment twice within 4 days., Results: Repeated-measures mixed linear models were used for between-group analysis, with mean differences and 95% confidence intervals (95% CIs) shown. Compared to controls, serum BNDF was higher in patients with CFS/FM (F = 15.703; mean difference 3.31 ng/ml [95% CI 1.65, 4.96]; P = 0.001), whereas BDNF DNA methylation in exon 9 was lower (F = 7.543; mean difference -2.16% [95% CI -3.93, -0.83]; P = 0.007). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF levels (F = 7.137, β = -0.408 [95% CI -0.711, -0.105]; P = 0.009), which in turn predicted participants' symptoms (F = 14.410, β = 3.747 [95% CI 1.79, 5.71]; P = 0.001) and widespread hyperalgesia (F = 4.147, β = 0.04 [95% CI 0.01, 0.08]; P = 0.044)., Conclusion: Our findings indicate that sBDNF levels are elevated in patients with CFS/FM and that BDNF methylation in exon 9 accounts for the regulation of protein expression. Altered BDNF levels might represent a key mechanism explaining CFS/FM pathophysiology., (© 2020, American College of Rheumatology.)

Pain conditions are among the leading causes of global disability, impacting on global healthcare utilization (HCU). Health seeking behavior might be influenced by cognitive and emotional factors (CEF), which can be tackled by specific therapies. The purpose of this study was to systematically review the evidence concerning associations between CEF and HCU in people experiencing pain. Three databases were consulted: PubMed, Web of Science and EconLit. Risk of bias was assessed using the Downs and Black Checklist (modified). A total of 90 publications (total sample n = 59,719) was included after double-blind screening. In people experiencing pain, positive associations between general anxiety symptoms, depressive symptoms and catastrophizing and pain medication use were found. Additionally, there appears to be a relationship between general anxiety and depressive symptoms and opioid use. Symptom-related anxiety and psychological distress were found to be positively related with consulting behavior. Last, a positive association between use of complementary and alternative medicine and level of perceived symptom control was confirmed in people with pain. For other relationships no evidence or inconsistent findings were found, or they were insufficiently studied to draw firm conclusions, indicating that more research on this topic is needed.

Background: Exercise, a cornerstone in current treatments for people with musculoskeletal pain, elicits a phenomenon called exercise-induced hypoalgesia (EIH), which may result in reduced pain intensity and/or increased pain thresholds. However, EIH can be impaired in patients with musculoskeletal pain, and psychosocial factors may play a mediating role in EIH., Objective: The aim of this study was to systematically review the scientific literature regarding the association between psychosocial factors and EIH in healthy people and people with musculoskeletal pain., Methods: An extensive search in databases including Medline Ovid, Embase, Web of Science, PsycINFO Ovid, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost was carried out. Two reviewers independently carried out study selection, data extraction, and critical appraisal. Included studies analyzed the association or effect of psychosocial factors on EIH in adults with or without musculoskeletal pain., Results: Nine cross-sectional studies were included, 6 involving healthy people and 4 involving people with musculoskeletal pain; 1 study included both. Overall risk of bias was high. Different types of exercise bouts, psychosocial factors, and/or outcome measures were used across studies. In healthy people and people with musculoskeletal pain, most studies did not find an association between psychosocial factors and EIH. However, 1 study involving musculoskeletal pain and 2 studies with healthy people did find a significant association., Conclusion: Due to poor quality and heterogeneity between studies, no conclusions can be drawn regarding whether psychosocial factors are associated with EIH or not. This review includes recommendations and directions for further research to investigate the role of psychosocial factors on EIH., (© 2020 World Institute of Pain.)

Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic mechanisms in people with pain. Four databases have been interrogated: MEDLINE, The Cochrane Central Register of Controlled Trial, Scopus, and Web of Science, following PRISMA guidelines in conducting study selection and assessment. Thirty-seven studies were included. Studies explored epigenetics in conditions such as fibromyalgia, CRPS, neuropathies, or osteoarthritis. Research focussed on genome-wide and gene-specific DNA methylation, and miRNA expression. Bioinformatics analyses exploring miRNA-associated molecular pathways were also performed. Several genes already known for their role in pain (BDNF, HDAC4, PRKG1, IL-17, TNFRSF13B, etc.), and several miRNAs linked to inflammatory regulation, nociceptive signalling and protein kinases functions have been found to differ significantly between people with chronic pain and healthy controls. Although the studies included were cross-sectional in nature, and no conclusion on causal links between epigenetic changes and pain could be drawn, we summarised the large amount of data available in literature on the topic, highlighting results that have been replicated by independent investigations. The field of pain epigenetics appears very exciting and has all the potential to lead to remarkable scientific advances. However, high-quality, well-powered, longitudinal studies are warranted. PERSPECTIVE: Though more high-quality research is needed, available research exploring epigenetic mechanisms or miRNAs in people with pain shows that genes regulating synaptic plasticity and excitability, protein kinases, and elements of the immune system might hold great potential in understanding the pathophysiology of different conditions., (Copyright © 2019 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

This article explores the effectiveness of a newly developed Pain Neuroscience Education program for children (PNE4Kids) with functional abdominal pain disorder (FAPD). Children (6-12 years) with FAPD were randomly assigned to 1) the experimental group ( n = 14), participating in one hypnotherapy session (i.e., usual care) and one additional PNE4Kids session, or 2) the control group ( n = 14), participating in two hypnotherapy sessions. Parental pain catastrophizing, the child's functional disability (parental-proxy), pain-related fear (parent-proxy) and pain intensity, were assessed at baseline and one and three weeks after each therapy session. Pressure algometry and a conditioned pain modulation paradigm were performed at baseline and three weeks after completion of the last therapy session. Parents from both the experimental as well as the control group showed significantly less parental pain catastrophizing ( p < 0.01). Children showed significantly less functional disability ( p < 0.05), pain-related fear ( p < 0.01) and local pressure pain sensitivity ( p < 0.05) at short-term follow-up (three weeks after last intervention) in both groups. No significant ( p > 0.05) between-group differences were found. Hypnotherapy combined with PNE4Kids did not result in better clinical outcomes compared to hypnotherapy alone. Study limitations include the application of one single PNE4Kids session and the short follow-up time.

Introduction: Despite the worldwide increase in prevalence of chronic pain and the subsequent scientific interest, researchers studying the brain and brain mechanisms in pain patients have not yet clearly identified the exact underlying mechanisms. Quantifying the neuronal interactions in electrophysiological data could help us gain insight into the complexity of chronic pain. Therefore, the aim of this study is to examine how different underlying pain states affect the processing of nociceptive information., Methods: Twenty healthy participants, 20 patients with non-neuropathic low back-related leg pain and 20 patients with neuropathic failed back surgery syndrome received nociceptive electrical stimulation at the right sural nerve with simultaneous electroencephalographic recordings. Dynamic Causal Modeling (DCM) was used to infer hidden neuronal states within a Bayesian framework., Results: Pain intensity ratings and stimulus intensity of the nociceptive stimuli did not differ between groups. Compared to healthy participants, both patient groups had the same winning DCM model, with an additional forward and backward connection between the somatosensory cortex and right dorsolateral prefrontal cortex., Discussion: The additional neuronal connection with the prefrontal cortex as seen in both pain patient groups could be a reflection of the higher attention towards pain in pain patients and might be explained by the higher levels of pain catastrophizing in these patients., Conclusion: In contrast to the similar pain intensity ratings of an acute nociceptive electrical stimulus between pain patients and healthy participants, the brain is processing these stimuli in a different way., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chronic pain has a tremendous personal and socioeconomic impact and remains difficult to treat. Therefore, it is important to provide an update on the current understanding regarding lifestyle factors in people with chronic pain across the lifespan. Lifestyle factors such as physical (in)activity, sedentary behavior, stress, poor sleep, unhealthy diet, and smoking are associated with chronic pain severity and sustainment. This applies to all age categories, that is, chronic pain across the lifespan. Yet current treatment options often do not or only partly address the many lifestyle factors associated with chronic pain or attempt to address them in a standard format rather than providing an individually tailored multimodal lifestyle intervention. The evidence regarding lifestyle factors is available in adults, but limited in children and older adults having chronic pain, providing important avenues for future research. In conclusion, it is proposed that treatment approaches for people with chronic pain should address all relevant lifestyle factors concomitantly in an individually-tailored multimodal intervention. Ultimately, this should lead to improved outcomes and decrease the psychological and socioeconomic burden of chronic pain. Level of Evidence: IV., (© 2019 American Academy of Physical Medicine and Rehabilitation.)

Objective: When evaluating sensory dysfunctions and pain mechanisms in patients with low back pain (LBP), a specific subgroup of patients with radicular symptoms is often excluded. Comparative studies that evaluate sensory sensitivity in patients with a dominant nociceptive and neuropathic pain component are rarely performed. Therefore, the goal of this study was to examine differences in electrical thresholds and conditioned pain modulation (CPM) between patients with low back-related leg pain (LBRLP) and patients with failed back surgery syndrome (FBSS)., Design: Cross-sectional study., Setting: University Hospital Brussels., Subjects: Twenty-one patients with LBRLP and 21 patients with FBSS were included., Methods: Electrical detection thresholds (EDTs), electrical pain thresholds (EPTs), and CPM were evaluated on the symptomatic and nonsymptomatic sides. Within- and between-group differences were evaluated for all parameters., Results: No between-group differences were found for EDT and EPT at both sides. On the nonsymptomatic side, a significantly lower CPM effect was found in the FBSS group (P = 0.04). The only significant within-group difference was an increased EDT at the symptomatic side in patients with FBSS (P = 0.01)., Conclusions: LBP patients with a primary neuropathic pain component revealed altered detection sensitivity at the symptomatic side, without severe indications for altered nociceptive processing, compared with LBP patients without a dominant neuropathic pain component. Endogenous modulation is functioning in LBP patients, although it is possible that it might only be functioning partially in patients with a dominant neuropathic pain component., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)