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.

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.

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.

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.

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.

Chronic Pain in Breast Cancer Survivors: Nociceptive, Neuropathic, or Central Sensitization Pain?

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

Hyperexcitability of the Central Nervous System in Children with Chronic Pain: A Systematic Review.

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

Prevalence of aromatase inhibitor-induced arthralgia in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Although aromatase inhibitors have proven to be an effective treatment of hormone receptor-positive breast cancer in postmenopausal women, aromatase inhibitor-induced arthralgia (AIA) is an adverse event associated with low compliance with treatment. The aim of this literature study is to assess the prevalence of AIA and to provide an overview of significant predictors for the development of AIA. METHODS: A systematic review was conducted using PubMed, Cochrane Library and Web of Science. A meta-analysis was performed and heterogeneity has been investigated by moderator analyses. The meta-analysis was repeated with studies that were considered as best evidence, i.e. studies with an above-average score on the STROBE checklist. RESULTS: Twenty-one studies (13,177 participants) were included. Prevalence rates ranged from 0.200 to 0.737. Meta-analysis resulted in a pooled estimate of 0.459 (95% CI = [0.397-0.520) with a high heterogeneity (I 2 = 98%). Moderator analysis showed no differences regarding heterogeneity. Predictors for the development of AIA included a body mass index of 25-30 kg/m2 (OR = 0.33), taxane-based chemotherapy (OR = 4.08), stage III cancer (OR = 0.32) and a duration of menopause of 5-10 years (OR = 1.10) or >10 years (OR = 0.44-3.29) (An OR <1 indicates a predictor of lower risk of AIA). DISCUSSION: Despite the established benefits of AI, an important portion of the patients experiences AIA. More research is needed to investigate the efficacy of treatments such as exercise therapy for AIA.

Risk factors of pain in breast cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Breast cancer remains the number 1 lethal malignancy in women. With rising incidence and decreased mortality, the number of breast cancer survivors has increased. Consequently, sequelae, such as pain, are becoming more important. PURPOSE: The purpose of this study was to identify risk factors for the development of pain in breast cancer survivors. METHODS: PubMed and Web of Science were systematically screened for studies encompassing risk factors for the development of pain in breast cancer survivors. Meta-analyses were carried out for risk factors described in more than one article. Moderator analysis was performed in case of high heterogeneity (I 2 > 50%) across studies. RESULTS: Seventeen studies were found eligible. Meta-analyses were performed for 17 factors. Significant differences for the odds of developing chronic pain were found for BMI (overall OR: 1.34, 95%CI 1.08-1.67, p = 0.008), education (overall OR: 1.23, 95%CI 1.07-1.42, p = 0.005), lymphedema (overall OR: 2.58, 95%CI 1.93-3.46, p < 0.00001), smoking status (overall OR: 0.75, 95%CI 0.62-0.92, p = 0.005), axillary lymph node dissection (overall OR: 1.25, 95%CI 1.04-1.52, p = 0.02), chemotherapy (overall OR: 1.44, 95%CI 1.24-1.68, p < 0.00001), and radiotherapy (overall OR: 1.32, 95%CI 1.17-1.48, p < 0.00001). After performing moderator analyses for age, comorbidities, hormone therapy, and breast surgery, hormone therapy became a significant risk factor as well (overall OR: 1.33, 95%CI 1.15-1.54, p = 0.0001). CONCLUSION: BMI > 30, education < 12-13 years, lymphedema, not smoking, axillary lymph node dissection, chemotherapy, hormone therapy, and radiotherapy were significantly associated with higher odds for the development of chronic pain, with lymphedema being the biggest risk factor. Lack of uniformity across the studies in defining pain, follow-up, measurement tools, and cut-off values for the diagnosis of pain was noted, resulting in greater inter-study variability.

Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain.

BACKGROUND: In addition to fatigue, pain is the most frequent persistent symptom in cancer survivors. Clear guidelines for both the diagnosis and treatment of pain in cancer survivors are lacking. Classification of pain is important as it may facilitate more specific targeting of treatment. In this paper we present an overview of nociceptive, neuropathic and central sensitization pain following cancer treatment, as well as the rationale, criteria and process for stratifying pain classification. MATERIAL AND METHODS: Recently, a clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain was developed, based on a large body of research evidence and international expert opinion. We, a team of 15 authors from 13 different centers, four countries and two continents have applied this classification algorithm to the cancer survivor population. RESULTS: The classification of pain following cancer treatment entails two steps: (1) examining the presence of neuropathic pain; and (2) using an algorithm for differentiating predominant nociceptive and central sensitization pain. Step 1 builds on the established criteria for neuropathic pain diagnosis, while Step 2 applies a recently developed clinical method for classifying any pain as either predominant central sensitization pain, neuropathic or nociceptive pain to the cancer survivor population. CONCLUSION: The classification criteria allow identifying central sensitization pain following cancer treatment. The recognition of central sensitization pain in practice is an important development in the integration of pain neuroscience into the clinic, and one that is relevant for people undergoing and following cancer treatment.

Effect of perceived injustice-targeted pain neuroscience education compared with biomedically focused education in breast cancer survivors: a study protocol for a multicentre randomised controlled trial (BCS-PI trial).

INTRODUCTION: Current treatments for pain in breast cancer survivors (BCSs) are mostly biomedically focused rather than biopsychosocially driven. However, 22% of BCSs with pain are experiencing perceived injustice, which is a known predictor for adverse pain outcomes and opioid prescription due to increased maladaptive pain behaviour. Educational interventions such as pain neuroscience education (PNE) are suggested to target perceived injustice. In addition, motivational interviewing can be an effective behavioural change technique. This trial aims to examine whether perceived injustice-targeted PNE with the integration of motivational interviewing is superior to biomedically focused pain education in reducing pain after 12 months in BCS with perceived injustice and pain. In addition, improvements in quality of life, perceived injustice and opioid use are evaluated, and a cost-effectiveness analysis will finally result in a recommendation concerning the use of perceived injustice-targeted PNE in BCSs with perceived injustice and pain. METHODS AND ANALYSIS: This two-arm multicentre randomised controlled trial will recruit female BCS (n=156) with pain and perceived injustice. Participants will be randomly assigned to perceived injustice-targeted PNE or biomedically focused pain education in each centre. Both interventions include an online session, an information leaflet and three one-to-one sessions. The primary outcome (pain), secondary outcomes (quality of life, perceived injustice and outcomes for cost-effectiveness analysis) and explanatory outcomes (pain phenotyping, sleep, fatigue and cognitive-emotional factors) will be assessed at baseline and at 0, 6, 12 and 24 months postintervention using self-reported questionnaires online. Treatment effects over time will be evaluated using linear mixed model analyses. Additionally, a cost-utility analysis will be done from a healthcare payer and societal perspective. ETHICS AND DISSEMINATION: The ethical agreement was obtained from the Main Ethics Committee (B.U.N.1432020000068) at the University Hospital Brussels and all other participating hospitals. Study results will be disseminated through presentations, conferences, social media, press and journals. TRIAL REGISTRATION NUMBER: NCT04730154.

Exercise therapy for knee osteoarthritis pain: how does it work? A study protocol for a randomised controlled trial.

INTRODUCTION: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA. METHODS AND ANALYSIS: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study. ETHICS AND DISSEMINATION: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians. TRIAL REGISTRATION NUMBER: NCT04362618.

The effect of psychologically informed practice with behavioural graded activity in cancer survivors: systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to determine the effectiveness of psychologically informed practice (PIP) with behavioural graded activity (BGA) compared to (1) waitlist controls (WLC), (2) other interventions (OI), (3) PIP alone or (4) BGA alone in cancer patients and survivors (CPaS). METHODS: PubMed, Web of Science and Embase were screened for randomised controlled trials encompassing BGA + PIP in CPaS. Effect sizes were inventoried for outcomes regarding physical activity (PA), quality of life (QoL) and debilitating symptoms (DS), which were assessed at four time points: post-intervention (PI), follow-up F1 (1 to 3 months), F2 (4 to 6 months) and F3 (> 6 months). The quality of the evidence was classified by the GRADE approach. RESULTS: Thirty-three studies were found eligible, comprising 4330 participants. Significant effects with low heterogeneity of PIP + BGA comparing to WLC were found for anxiety (SMD - 1.29 [-1.71; - 0.86]), depression (SMD - 0.79 [- 1.10; - 0.48]), functional impairment (SMD - 0.72 [- 0.95; - 0.50]), PA (self-reported: (SMD - 0.58 [- 0.84; - 0.32]) and objectively measured: (SMD - 0.51 [- 0.90; - 0.13])) and social impairment (SMD - 0.33 [- 0.58; - 0.08]). When comparing PIP + BGA to OI, fatigue (SMD - 0.35 [- 0.51; - 0.20]) and PA (SMD - 0.26 [- 0.41; - 0.11]) at PI, and fatigue (SMD - 0.34 [- 0.58; - 0.10]) at F1 were found significant with low heterogeneity. No significant effects were observed in the meta-analyses of studies comparing PIP + BGA to BGA or PIP alone. CONCLUSIONS: PIP with BGA has a favourable effect on DS, PA and QoL in CPaS when compared to non-behavioural interventions such as WLC, usual care and education. However, further research is needed on 'how' and 'when' PIP + BGA should be provided in cancer rehabilitation. IMPLICATIONS FOR CANCER SURVIVORS: PIP + BGA has the potential to facilitate CPaS to reach the recommended amount of PA and reduce DS.

Perceived Injustice in Cancer Survivors: Population-Specific Cut-Off Score and Relations with Personal Factors, Symptoms and Quality of Life-A Cross-Sectional Study.

Fatigue and pain are the most common side effects impacting quality of life (QoL) in cancer survivors. Recent insights have shown that perceived injustice (PI) can play a substantial role in these side effects, but research on cancer survivors is scarce. Furthermore, guidelines for recognizing clinically relevant levels of PI in cancer survivors are missing. The aims of this study are to provide a clinically relevant cut-off for PI and to explore relationships between personal characteristics, symptoms, and QoL with PI. This multicenter, cross-sectional study uses the Injustice Experience Questionnaire (IEQ), Numeric Pain Rating Scale (NPRS), Patient-Specific Complaints (PSC), Multidimensional Fatigue Index (MFI), and European Organization for Research and Treatment of Cancer QoL Questionnaire-C30 (EORTC-QLQ-C30). A clinical cut-off for PI was identified based on the 75th percentile of IEQ scores. Univariate and multivariate regressions explored the relationship between PI and personal characteristics (sex, age, cancer type, treatment type), symptoms (pain intensity, fatigue), and QoL (daily activity complaints, cancer-related QoL). Cancer survivors (n = 121) were included, and a cut-off of 20 was identified. Significant indirect associations were found between chemotherapy, NPRS, PSC, MFI, and EORTC-QLQ-C30 with PI. In the multivariate model, only MFI (B = 0.205; 95% CI: 0.125-0.018) and age (B = 0.086; 95% CI: -0.191-0.285) maintained a significant association with PI.

The Prevalence of Perceived Injustice and Factors Associated With Perceived Injustice in People With Pain: A Systematic Review With Meta-analysis.

BACKGROUND: Perceived injustice (PI) is a multidimensional appraisal cognition comprising the severity of loss consequent to injury, blame, a sense of unfairness, and/or irreparability of loss. PI gained increasing interest in pain research since it potentially contributes to the experience and burden of (chronic) pain. OBJECTIVES: This systematic review aimed to determine the prevalence of PI and factors associated with PI in people with pain. STUDY DESIGN: Systematic review with meta-analysis. METHODS: Web of Science, PubMed, and Embase were screened for cross-sectional or cohort studies encompassing human patients who were diagnosed with a condition causing pain and reported prevalence rates for PI and/or associations between a factor and PI. Meta-analyses were carried out, and subgroup analyses were undertaken based on the methodological quality of the studies, the type of pain population, and whether the outcome measure was valid or not in case of heterogeneity (P < 0.05). RESULTS: Fifty-four studies were found eligible. The prevalence of PI ranged from 23% to 77% (I2 = 99%, P < 0.001). Association with PI, assessed using the Injustice Experienced Questionnaire, were found with pain catastrophizing (pooled Pearson's r [rp] = 0.66 [0.64, 0.69], P < 0.00001), posttraumatic stress (rp = 0.63 [0.59, 0.67], P < 0.00001), anger (rp = 0.59 [0.49, 0.67], P < 0.00001), anxiety (rp = 0.59 [0.52, 0.64], P < 0.00001), pain acceptance (rp = -0.59 [-0.66, -0.49], P < 0.00001), depressive symptoms (rp = 0.57 [0.52, 0.60], P < 0.00001), kinesiophobia (rp = 0.57 [0.50, 0.64], P < 0.00001), academic functioning (rp = -0.54 [-0.65, -0.41], P < 0.00001), disability (rp = 0.53 [0.47, 0.59], P < 0.00001), emotional functioning (rp = -0.52 [-0.64, -0.39], P < 0.00001), pain interference (rp = 0.49 [0.35, 0.60], P < 0.00001), state anger (rp = 0.48 [0.41, 0.54], P < 0.00001), mental functioning (rp = -0.48 [-0.57, -0.38], P < 0.00001), symptoms of central sensitization (rp = 0.47 [0.39, 0.55], P < 0.00001), social functioning (rp = -0.47 [-0.60, -0.31], P < 0.00001), and physical functioning (rp = -0.43 [-0.53, -0.33], P < 0.00001), pain perceptions (rp = 0.40 [0.40, 0.64], P < 0.00001), trait anger (rp = 0.40 [0.29, 0.49], P < 0.00001), pain intensity (rp = 0.37 [0.33, 0.42], P < 0.00001), and anger inhibition (rp = 0.35 [0.26, 0.43], P < 0.00001). LIMITATIONS: Some articles had to be excluded due to the absence of a full-text version. The findings can largely be applied to developed and high-income countries, but further research is needed in developing countries. Also, no validated cutoff values were available for the National Institutes of Health to determine the methodological quality of the included studies. Lastly, high heterogeneity was observed in many of the performed analyses. However, this was addressed by performing subgroup analyses, which could decrease heterogeneity in some cases. CONCLUSIONS: The prevalence of PI was >= 33% in 75% of the studies indicating that PI is important to consider in people with pain. There is evidence for the association of PI with psychological, pain, and quality of life characteristics in people with pain. The associations of PI with personal, injury, and recovery characteristics were overall not significant or negligible.

Personalised rehabilitation to improve return to work in patients with persistent spinal pain syndrome type II after spinal cord stimulation implantation: a study protocol for a 12-month randomised controlled trial-the OPERA study.

BACKGROUND: For patients with therapy-refractory persistent spinal pain syndrome type II (PSPS-T2), spinal cord stimulation (SCS) may serve as an effective minimally invasive treatment. Despite the evidence that SCS can improve return to work (RTW), only 9.5 to 14% of patients implanted with SCS are effectively capable of returning to work. Thus, it seems that current post-operative interventions are not effective for achieving RTW after SCS implantation in clinical practice. The current objective is to examine whether a personalised biopsychosocial rehabilitation programme specifically targeting RTW alters the work ability in PSPS-T2 patients after SCS implantation compared to usual care. METHODS: A two-arm, parallel-group multicentre randomised controlled trial will be conducted including 112 patients who will be randomised (1:1) to either (a) a personalised biopsychosocial RTW rehabilitation programme of 14 weeks or (b) a usual care arm, both with a follow-up period until 12 months after the intervention. The primary outcome is work ability. The secondary outcomes are work status and participation, pain intensity, health-related quality of life, physical activity and functional disability, functional capacities, sleep quality, kinesiophobia, self-management, anxiety, depression and healthcare expenditure. DISCUSSION: Within the OPERA project, we propose a multidisciplinary personalised biopsychosocial rehabilitation programme specifically targeting RTW for patients implanted with SCS, to tackle the high socio-economic burden of patients that are not re-entering the labour market. The awareness is growing that the burden of PSPS-T2 on our society is expected to increase over time due to the annual increase of spinal surgeries. However, innovative and methodologically rigorous trials exploring the potential to decrease the socio-economic burden when patients initiate a trajectory with SCS are essentially lacking. TRIAL REGISTRATION: ClinicalTrials.gov NCT05269212. Registered on 7 March 2022.

Combining Stress Management With Pain Neuroscience Education and Exercise Therapy in People With Whiplash-Associated Disorders: A Clinical Perspective.

Individuals classified as having whiplash-associated disorder (WAD) grade II, which reflects approximately 93% of people with WAD who are commonly managed by health care professionals, exhibit both physical (eg, pain and disability) and psychological (eg, fear of movement, anxiety, posttraumatic stress) problems that, in approximately 50% of cases, persist beyond 3 months. There is still much ongoing debate regarding factors predictive of poor recovery. The strongest associations have been found for high initial pain and disability following whiplash injury. In addition, a growing body of evidence supports the clinical importance of characteristic features, such as disturbed nociceptive processing (eg, local or general hyperalgesia to cold and mechanical stimuli), inefficient cognitions and beliefs about pain/movement/recovery, and posttraumatic stress symptoms, in the development and maintenance of physical and psychological manifestations in individuals with WAD. For this reason, the field shifted away from single interventions that mainly follow a biomedical approach, such as exercise therapy and activity programs, to gold standard multimodal care (at least 2 distinct therapeutic modalities given by 1 or more health care professionals) that acknowledges the biopsychological nature of WAD. To date, there exist several multimodal care approaches to managing WAD; however, for most, the efficacy has been found to be rather limited. One may argue that the limited success of some approaches can be attributed to the fact that they focused mainly on rehabilitating the physical symptoms (eg, pain, disability) rather than also the associated cognitive (eg, catastrophizing) and psychological (eg, posttraumatic stress symptoms) symptoms of the condition, leaving much room for improvement. In this article, current and previous evidence is used to explain why and how a comprehensive and multimodal treatment for people with WAD-consisting of a combination of pain neuroscience education, cognition-targeted exercise therapy, and stress management-can be applied in clinical practice.

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

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

Lifestyle and Pain following Cancer: State-of-the-Art and Future Directions.

This review discusses chronic pain, multiple modifiable lifestyle factors, such as stress, insomnia, diet, obesity, smoking, alcohol consumption and physical activity, and the relationship between these lifestyle factors and pain after cancer. Chronic pain is known to be a common consequence of cancer treatments, which considerably impacts cancer survivors' quality of life when it remains untreated. Improvements in lifestyle behaviour are known to reduce mortality, comorbid conditions (i.e., cardiovascular diseases, other cancer, and recurrence) and cancer-related side-effects (i.e., fatigue and psychological issues). An inadequate stress response plays an important role in dysregulating the body's autonomic, endocrine, and immune responses, creating a problematic back loop with pain. Next, given the high vulnerability of cancer survivors to insomnia, addressing and treating those sleep problems should be another target in pain management due to its capacity to increase hyperalgesia. Furthermore, adherence to a healthy diet holds great anti-inflammatory potential for relieving pain after cancer. Additionally, a healthy diet might go hand in hand with weight reduction in the case of obesity. Consuming alcohol and smoking have an acute analgesic effect in the short-term, with evidence lacking in the long-term. However, this acute effect is outweighed by other harms on cancer survivors' general health. Last, informing patients about the benefits of an active lifestyle and reducing a sedentary lifestyle after cancer treatment must be emphasised when considering the proven benefits of physical activity in this population. A multimodal approach addressing all relevant lifestyle factors together seems appropriate for managing comorbid conditions, side-effects, and chronic pain after cancer. Further research is needed to evaluate whether modifiable lifestyle factors have a beneficial influence on chronic pain among cancer survivors.

Are Reports of Pain, Disability, Quality of Life, Psychological Factors, and Central Sensitization Related to Outcomes of Quantitative Sensory Testing in Patients Suffering From Chronic Whiplash Associated Disorders?

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.