Phenotyping of chronic pain in breast cancer survivors: an original study using the cancer pain phenotyping (CANPPHE) Network multidisciplinary international guidelines.

PURPOSE: The primary aim of this cross-sectional study is to examine the prevalence of pain phenotypes in breast cancer survivors (BCS). A secondary aim entails examining whether health related quality of life differs between the main pain phenotypes in BCS. METHODS: BCS who experienced chronic pain were asked to complete the numeric pain rating scale for pain, Margolis pain diagram, and short form 36 (SF-36). Following administration of questionnaires and quantitative sensory examinations were applied. To determine the prevalence of the predominant type of pain, a recently proposed classification system by the Cancer Pain Phenotyping (CANPPHE) Network was used. RESULTS: Of the 86 female participants, 19 (22.09%) had dominant neuropathic pain, 18 (20.93%) had dominant nociceptive pain and 14 (16.28%) had dominant nociplastic pain. 35 participants (40.70%) were classified as having mixed pain. One-way ANOVA revealed a significant difference between the four pain groups for the SF-36 general health (F = 3.205, p = 0.027), social functioning (F = 4.093, p = 0.009), and pain (F = 3.603, p = 0.017) subscale scores. CONCLUSION: This study found that pain in BCS was mostly of mixed phenotype, followed by predominantly neuropathic and nociplastic pain. Furthermore, it was found that, compared to BCS with predominant neuropathic and nociceptive pain, BCS with predominant nociplastic pain have lower health related quality of life in the areas of bodily pain and social functioning.

Development of an interdisciplinary training program about chronic pain management with a cognitive behavioural approach for healthcare professionals: part of a hybrid effectiveness-implementation study.

BACKGROUND: Many applied postgraduate pain training programs are monodisciplinary, whereas interdisciplinary training programs potentially improve interdisciplinary collaboration, which is favourable for managing patients with chronic pain. However, limited research exists on the development and impact of interdisciplinary training programs, particularly in the context of chronic pain. METHODS: This study aimed to describe the development and implementation of an interdisciplinary training program regarding the management of patients with chronic pain, which is part of a type 1 hybrid effectiveness-implementation study. The targeted groups included medical doctors, nurses, psychologists, physiotherapists, occupational therapists, dentists and pharmacists. An interdisciplinary expert panel was organised to provide its perception of the importance of formulated competencies for integrating biopsychosocial pain management with a cognitive behavioural approach into clinical practice. They were also asked to provide their perception of the extent to which healthcare professionals already possess the competencies in their clinical practice. Additionally, the expert panel was asked to formulate the barriers and needs relating to training content and the implementation of biopsychosocial chronic pain management with a cognitive behavioural approach in clinical practice, which was complemented with a literature search. This was used to develop and adapt the training program to the barriers and needs of stakeholders. RESULTS: The interdisciplinary expert panel considered the competencies as very important. Additionally, they perceived a relatively low level of healthcare professionals' possession of the competencies in their clinical practice. A wide variety of barriers and needs for stakeholders were formulated and organized within the Theoretical Domain Framework linked to the COM-B domains; 'capability', 'opportunity', and 'motivation'. The developed interdisciplinary training program, including two workshops of seven hours each and two e-learning modules, aimed to improve HCP's competencies for integrating biopsychosocial chronic pain management with a cognitive behavioural approach into clinical practice. CONCLUSION: We designed an interdisciplinary training program, based on formulated barriers regarding the management of patients with chronic pain that can be used as a foundation for developing and enhancing the quality of future training programs.

Exercise-induced effects on inflammatory markers and brain-derived neurotrophic factor in patients with knee osteoarthritis. A systematic review with meta-analysis.

Background: In the pathogenesis of knee osteoarthritis (KOA), inflammatory mediators play an important role. However, the precise underlying mechanism by which regular exercise therapy (ET) exert effects on the immune system in KOA patients is unknown. Objectives: The aim of this systematic review was to investigate the basal and acute effects of ET on inflammatory biomarkers and brain derived neurotrophic factor (BDNF) in KOA patients. Methods: PubMed, Web Of Science and PEDro were systematically searched for appropriate studies. If possible, a meta-analysis was performed or an approximation of the effect size (ES) was calculated. Risk of bias was scored using the Cochrane ROB 2.0 or ROBINS-tools. Results: Twenty-one studies involving 1374 participants were included. Fifteen articles focused on basal exercise effects, four on acute effects, and two on both. Biomarker analysis (n=18) was performed in synovial fluid (n=4) or serum/plasma (n=17). A meta-analysis demonstrated that basal CRP was reduced in KOA patients 6-18 weeks weeks after ET (MD: -0.17;95%CI[-0.31;-0.03]), while IL-6 (MD: 0.21;95%CI[-0.44;0.85]), and TNF-α (MD: -0.57;95%CI[-1.47;0.32]), levels did not significantly change. Also, sTNFR1/2 did not change significantly after ET. For other biomarkers, insufficient data were available to perform a meta-analysis. Nevertheless, a low degree of evidence was found for a decrease in IL-6 (ES:-0.596 & -0.259 & -0.513), an increase in sTNFR1 (ES:2.325), a decrease in sTNFR2 (ES:-0.997) and an increase in BDNF (ES:1.412). Locally, intra-articular IL-10 (ES:9.163) increased, and IL1ß (ES:-6.199) and TNF-α decreased (ES:-2.322) after ET. An acute exercise session elicited a myokine response (ES IL-6:0.314), and an increase in BDNF (no ES-data). No inflammatory effect (ES CRP:0.052; ES TNF-α:-0.019 & 0.081) following an acute bout of training was found. However, a single bout of exercise elicited a decrease in intra-articular IL-10 (no ES-data). Conclusion: ET can induce circulatory and intra-articular anti-inflammatory effects in patients with KOA. The antiinflammatory properties have important implications for informing these patients and clinicians about the underlying effects of ET.

Effect of perioperative pain neuroscience education in people undergoing surgery for lumbar radiculopathy: a multicentre randomised controlled trial.

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.

Towards precision pain medicine for pain after cancer: the Cancer Pain Phenotyping Network multidisciplinary international guidelines for pain phenotyping using nociplastic pain criteria.

Pain after cancer remains underestimated and undertreated. Precision medicine is a recent concept that refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics. Applying this to pain after cancer, the ability to classify post-cancer pain into the three major pain phenotypes (i.e. nociceptive, neuropathic, and nociplastic pain) and tailor pain treatment accordingly, is an emerging issue. This is especially relevant because available evidence suggests that nociplastic pain is present in an important subgroup of those patients experiencing post-cancer pain. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system for nociplastic pain account for the need to identify and correctly classify patients according to the pain phenotype early in their treatment. These criteria are an important step towards precision pain medicine with great potential for the field of clinical oncology. Within this framework, the Cancer Pain Phenotyping (CANPPHE) Network, an international and interdisciplinary group of oncology clinicians and researchers from seven countries, applied the 2021 IASP clinical criteria for nociplastic pain to the growing population of those experiencing post-cancer pain. A manual is provided to allow clinicians to differentiate between predominant nociceptive, neuropathic, or nociplastic pain after cancer. A seven-step diagnostic approach is presented and illustrated using cases to enhance understanding and encourage effective implementation of this approach in clinical practice.

Experimental Pain Measurements Do Not Relate to Pain Intensity and Pain Cognitions in People Scheduled for Surgery for Lumbar Radiculopathy.

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.

Sensitization symptoms are associated with psychological and cognitive variables in COVID-19 survivors exhibiting post-COVID pain.

OBJECTIVE: To investigate the association between demographic, clinical, psychological, cognitive, and health-related variables and the Central Sensitization Inventory (CSI) in previously hospitalized COVID-19 survivors exhibiting "de novo" post-COVID pain. METHODS: Seventy-seven (n = 77) COVID-19 survivors with "de novo" post-COVID pain completed demographic (age, height, and weight), clinical (duration and intensity of the pain), psychological (depressive/anxiety levels and sleep quality), cognitive (catastrophizing and kinesiophobia levels), and health-related quality of life variables as well as the CSI. A multivariable correlation analysis was conducted to determine the association between variables, and a stepwise multiple linear regression model was performed to identify CSI predictors. RESULTS: Patients were assessed a mean of 6.0 (SD 0.8) months after hospital discharge. Twenty-six (33.7%) individuals showed indications of sensitization-associated symptoms (CSI score ≥40 points). The CSI score was positively associated with pain intensity (r: 0.371), anxiety (r: 0.784), depressive (r: 0.709), catastrophizing (r: 0.620), and kinesiophobia (r: 0.359) levels (all, p < 0.001). The stepwise regression analysis revealed that 60.2% of CSI was explained by anxiety levels and pain intensity. CONCLUSION: This study found that psychological and cognitive variables were associated with the CSI score in previously hospitalized COVID-19 survivors with "de novo" post-COVID pain. Anxiety levels and the intensity of pain symptoms were independently associated with CSI score suggesting a significant overlap with psychological construct. The "de novo" post-COVID pain association with CSI may indicate changes in the pain processing important for managing the pain.

Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and Fibromyalgia.

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-ß). RESULTS: COMT haplotypes were associated with DNA methylation in the S-COMT promoter, TGF-ß 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.

Diet can exert both analgesic and pronociceptive effects in acute and chronic pain models: a systematic review of preclinical studies.

BACKGROUND: Although diet is an essential aspect of human health, the link between diet and pain is still not well understood. Preclinical animal research provides information to understand underlying mechanisms that allow identifying the needs for human research. OBJECTIVES: This study aims to give a systematic overview of the current evidence from preclinical studies regarding the analgesic and pronociceptive effects of various diets in non-neuropathic, non-cancer, or non-visceral acute and chronic pain models. STUDY DESIGN: A systematic Review. SETTING: This study examined studies that investigate the analgesic and pronociceptive effects of various diets in non-neuropathic, non-cancer, or non-visceral acute and chronic pain models. METHODS: This review was conducted following the PRISMA guidelines and was registered in PROSPERO with the registration number CRD42019133473. The certainty of evidence was examined by a modified GRADE approach. RESULTS: After the screening process twenty-four eligible papers were included in this review. Nineteen studies examined acute pain, nine studies chronic inflammatory pain, and four studies assessed both acute and chronic pain models. LIMITATIONS: Due to the heterogeneity of the included studies, a meta-analysis was not included in this study. CONCLUSIONS: In animal models, excessive saturated, monounsaturated or omega-6 polyunsaturated fat ingestion and diets rich in fats and carbohydrates can decrease pain sensitivity in acute nociceptive pain, whereas it can induce mechanical allodynia and heat hyperalgesia in chronic inflammatory pain. Additionally, diets rich in anti-inflammatory ingredients, as well as a calorie-restricted diet can promote recovery from primary mechanical allodynia and heat hyperalgesia in chronic inflammatory pain.

Health-related quality of life deviations from population norms in patients with lumbar radiculopathy: associations with pain, pain cognitions, and endogenous nociceptive modulation.

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.

The mediating effect of pain catastrophizing and perceived injustice in the relationship of pain on health-related quality of life in breast cancer survivors.

BACKGROUND: The importance of cognitive appraisals in the effectiveness of pain coping is well established. Two key variables in these appraisal processes are pain catastrophizing (PC) and perceived injustice (PI), which are known to increase the risk of long-term disability and aggravate the pain-related distress through maladaptive behavioral responses. However, to date, the mediating effects of these appraisals have not been examined concurrently in the breast cancer survivor (BCS) population, nor have they been related to health-related quality of life (HRQoL). METHODS: Using cross-sectional data from 110 BCS, structural path analyses were used to examine the mediating effects of PC and PI in the relationship of pain on the HRQoL in BCS. RESULTS: Results demonstrated a significant direct effect of pain and PI on HRQoL combined with a significant indirect effect through PI, but not through PC. An increase in pain is suggested to result in a decrease in quality of life. On the other hand, an increase in pain also is suggested to increase the PI. A similar relation with PC was not retained as significant. CONCLUSION: The relative salience of PI as a mediator of HRQoL underscores the fact that PI is not only understudied but also underappreciated and undertreated in the BCS population. The results of our study warrant replication across longitudinal studies but continue to expand upon the evidence of the multifactorial nature of pain coping in BCS.

Electrical (Pain) Thresholds and Conditioned Pain Modulation in Patients with Low Back-Related Leg Pain and Patients with Failed Back Surgery Syndrome: A Cross-Sectional Pilot Study.

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.

Electroencephalography During Nociceptive Stimulation in Chronic Pain Patients: A Systematic Review.

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.

Processing of Laser-Evoked Potentials in Patients with Chronic Whiplash-Associated Disorders, Chronic Fatigue Syndrome, and Healthy Controls: A Case-Control Study.

OBJECTIVE: Laser-evoked potentials (LEPs) are among the reliable neurophysiological tools to investigate patients with neuropathic pain, as they can provide an objective account of the functional status of thermo-nociceptive pathways. The goal of this study was to explore the functioning of the nociceptive afferent pathways by examining LEPs in patients with chronic whiplash-associated disorders (cWAD), patients with chronic fatigue syndrome (CFS), and healthy controls (HCs). DESIGN: Case-control study. SETTING: A single medical center in Belgium. SUBJECTS: The LEPs of 21 patients with cWAD, 19 patients with CFS, and 18 HCs were analyzed in this study. METHODS: All participants received brief nociceptive CO2 laser stimuli applied to the dorsum of the left hand and left foot while brain activity was recorded with a 32-channel electroencephalogram (EEG). LEP signals and transient power modulations were compared between patient groups and HCs. RESULTS: No between-group differences were found for stimulus intensity, which was supraliminal for Aδ fibers. The amplitudes and latencies of LEP wave components N1, N2, and P2 in patients with cWAD and CFS were statistically similar to those of HCs. There were no significant differences between the time-frequency maps of EEG oscillation amplitude between HCs and both patient populations. CONCLUSIONS: EEG responses of heat-sensitive Aδ fibers in patients with cWAD and CFS revealed no significant differences from the responses of HCs. These findings thus do not support a state of generalized central nervous system hyperexcitability in those patients.

How Much Is Needed? Comparison of the Effectiveness of Different Pain Education Dosages in Patients with Fibromyalgia.

OBJECTIVE: To assess the effect of different dosages of pain neuroscience education (PNE) programs on central nociceptive processing in patients with fibromyalgia. Second, to compare the effects of different dosages of PNE programs on numerical pain rating scale (NPRS), disability, and psychological variables. DESIGN: Single-blind randomized controlled trial. SETTING: Three fibromyalgia centers in Spain (Valencia, Alcorcón, Alcalá de Henares). SUBJECTS: Seventy-seven patients with fibromyalgia. METHODS: Participants were randomized to four groups of PNE: 1) high-dose PNE (N = 20), 2) low-concentrated dose PNE (N = 20), 3) diluted low-dose PNE (N = 20), and (4) control treatment (N = 17), conducted in two 30-50-minute sessions in groups of four to six participants. Conditioned pain modulation (CPM), temporal summation (TS), and pressure pain thresholds (PPTs) were assessed at baseline and at three-month follow-up. Secondary outcome measures were the Fibromyalgia Impact Questionnaire, Pain Catastrophizing Scale, and Pain Anxiety Symptoms Scale. RESULTS: There were significant between-group differences for NPRS in favor of the groups receiving high-dose PNE, with a large effect size at three-month follow-up (P < 0.01, η2p = 0.170), but there were no significant differences between groups for the remaining variables (P > 0.05). All groups improved for central nociceptive processing, psychological variables, disability, and pain intensity (NPRS). CONCLUSIONS: In patients with fibromyalgia, higher dosages of PNE produced a larger improvement in pain severity at three-month follow-up than other dosages of PNE and biomedical education. However, PNE was not superior to biomedical education in the central nociceptive processing, disability, or psychological variables in patients with fibromyalgia.

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

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

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

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

Prevalence and risk factors of sleep disturbances in breast cancersurvivors: systematic review and meta-analyses.

BACKGROUND: Breast cancer remains the most frequently diagnosed malignancy among women worldwide, with rising incidence numbers. In Belgium, one out of eight women will be diagnosed with breast cancer. Fortunately, 80% of those breast cancer patients will still be alive 10 years after diagnosis due to improvements in screening and treatment strategies. However, an important portion of the breast cancer survivors (BCS) will face side effects, such as sleep disturbances, long after treatment ends. It has been demonstrated that untreated insomnia in BCS negatively impacts mood, physical symptoms, pain sensitivity, fatigue, and quality of life. Furthermore, insomnia is increasingly considered an independent risk factor for future depression in BCS. The importance of understanding sleep disturbances in cancer populations has been highlighted and recognized as warranting further research. Therefore, the purpose of this systematic review was to determine the prevalence and the risk factors for the development of sleep disturbances in BCS. METHODS: PubMed, Web of Science, and PEDro were systematically screened for studies encompassing data regarding the prevalence or risk factors of sleep disturbances in BCS. If possible, meta-analyses were performed. Subgroup analyses were undertaken based on the methodological quality, study design, type of sleep disturbance, and the use of a measurement tool with strong psychometric properties to investigate significant heterogeneity (I2 > 50%) across studies. RESULTS: A total of 27 studies were found eligible. The pooled estimate for sleep disturbances prevalence is 0.40 (95% confidence interval (CI) = [0.29-0.52], I2 = 100%, p < 0.00001) and ranged from 0.14 (95% CI = [0.04-0.24]) to 0.93 (95% CI = [0.91-0.95]). Subgroup analyses did not reduce the heterogeneity among studies. Meta-analyses were performed for seven risk factors. Significant differences for the odds of developing sleep disturbances were found for hot flashes (pooled OR (ORp) 2.25, 95% CI = [1.64-3.08], I2 = 0%, p = 0.90), race (ORp 2.31, 95% CI = [1.56-3.42], I2 = 0%, p = 0.47), and menopause (ORp 1.84, 95% CI = [1.11-3.06], I2 = 0%, p = 0.70). After withdrawing the studies that did not rely on the use of a measurement tool with strong psychometric properties, pain (ORp 2.31, 95% CI = [1.36-3.92], I2 = 27%, p = 0.25), depressive symptoms (ORp 3.20, 95% CI [2.32-4.42], I2 = 0%, p = 0.63), and fatigue (ORp 2.82, 95% CI = [1.98-4.02], I2 = 0%, p = 0.60) became significant as well, with a substantial decrease of heterogeneity. CONCLUSION: Prevalence for sleep disturbances ranged from 0.14 to 0.93 with the vast majority of the studies investigating insomnia and sleep-wake disturbances. High heterogeneity makes it difficult to draw firm conclusions. Pain, depressive symptoms, hot flashes, fatigue, non-Caucasian race, and menopausal status were significantly associated with increased odds for developing sleep disturbances.

Assessing Endogenous Pain Inhibition: Test-Retest Reliability of Exercise-Induced Hypoalgesia in Local and Remote Body Parts After Aerobic Cycling.

OBJECTIVE: Acute exercise can trigger a hypoalgesic response (exercise-induced hypoalgesia [EIH]) in healthy subjects. Despite promising application possibilities of EIH in the clinical context, its reliability has not been sufficiently examined. This study therefore investigated the between-session and within-subject test-retest reliability of EIH at local and remote body parts after aerobic cycling at a heart rate-controlled intensity. METHODS: Thirty healthy adults (15 women) performed 15 minutes of aerobic cycling in two sessions. Pressure pain thresholds (PPTs) were assessed at the leg (local), the back (semilocal), and the hand (remote) before, immediately after, and 15 minutes after exercise. Intraclass correlation coefficients (ICCs) were calculated for absolute and percent changes in PPT from baseline to immediately postexercise, and between-session agreement of EIH responders was examined. RESULTS: PPTs significantly increased at the leg during both sessions (all P < 0.001) and at the back during session 2 (P < 0.001), indicating EIH. Fair between-session reliability was shown for absolute changes at the leg (ICC = 0.54) and the back (ICC = 0.40), whereas the reliability of percent changes was poor (ICC < 0.33). Reliability at the hand was poor for both absolute and percent changes (ICC < 0.33). Agreement in EIH responders was not significant for EIH at the leg or the back (all P > 0.05). CONCLUSIONS: Our results suggest fair test-retest reliability of EIH after aerobic cycling for local and semilocal body parts, but only in men, demonstrating the need for more standardized methodological approaches to improve EIH as a clinical parameter.

When Environment Meets Genetics: A Clinical Review of the Epigenetics of Pain, Psychological Factors, and Physical Activity.

Epigenetic mechanisms represent a link between the environment and gene function. Recent research shows how early life stress, inflammation, and physical activity can influence gene expression through epigenetic mechanisms. Epigenetic changes-such as DNA methylation and microRNA interference-can be measured in humans and might soon become important biological markers. Epigenetic marks can accompany clinical assessment to measure the effectiveness of various interventions, such as exercise therapy. In addition, epigenetics is improving the understanding of important underlying mechanisms related to the central nervous system, the opioidergic system, and stress responses. Epigenetics is closing a gap in our explanatory abilities and should be implemented to broaden the field of rehabilitation sciences, promote a mechanism-based clinical reasoning, and develop new treatments. In the present review, we focused on epigenetic mechanisms related to pain, psychological factors (such as fear and anxiety), and physical activity, translating relevant findings from these 3 different, yet related, areas of cardinal importance for clinicians.