Personalized Multimodal Lifestyle Intervention as the Best-Evidenced Treatment for Chronic Pain: State-of-the-Art Clinical Perspective.

Chronic pain is the most prevalent disease worldwide, leading to substantial disability and socioeconomic burden. Therefore, it can be regarded as a public health disease and major challenge to scientists, clinicians and affected individuals. Behavioral lifestyle factors, such as, physical (in)activity, stress, poor sleep and an unhealthy diet are increasingly recognized as perpetuating factors for chronic pain. Yet, current management options for patients with chronic pain often do not address lifestyle factors in a personalized multimodal fashion. This state-of-the-art clinical perspective aims to address this gap by discussing how clinicians can simultaneously incorporate various lifestyle factors into a personalized multimodal lifestyle intervention for individuals with chronic pain. To do so the available evidence on (multimodal) lifestyle interventions targeting physical (in)activity, stress, sleep and nutritional factors, specifically, was reviewed and synthetized from a clinical point of view. First, advise is provided on how to design a personalized multimodal lifestyle approach for a specific patient. Subsequently, best-evidence recommendations on how to integrate physical (in)activity, stress, sleep and nutritional factors as treatment targets into a personalized multimodal lifestyle approach are outlined. Evidence supporting such a personalized multimodal lifestyle approach is growing, but further studies are needed.

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.

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.

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.

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 Perceived Injustice and Pain Catastrophizing in the Relationship of Pain on Fatigue and Sleep in Breast Cancer Survivors: A Cross-Sectional Study.

OBJECTIVE: Multidimensional aspects of pain have raised awareness about cognitive appraisals, such as perceived injustice (PI) and pain catastrophizing (PC). It has been demonstrated that they play an important role in patients' pain experience. However, the mediating effect of these appraisals has not been investigated in breast cancer survivors (BCS), nor have they been related to fatigue and sleep. METHODS: Cross-sectional data from 128 BCS were analysed by structural path analysis with the aim to examine the mediating effect of PI and PC in the relationship of pain on fatigue and sleep. RESULTS: The indirect mediating effects of PI on fatigue (CSI*PI = 0.21; P < .01 and VAS*PI = 1.19; P < .01) and sleep (CSI*PI = 0.31; P < .01 and VAS*PI = 1.74; P < .01) were found significant for both pain measures (Central Sensitization Inventory [CSI] and Visual Analogue Scale [VAS]). PC, on the other hand, only mediated the relationship between pain measured by VAS and fatigue (VAS*PC = 0.80; P = .03). Positive associations were found, indicating that higher pain levels are positively correlated with PI and PC, which go hand in hand with higher levels of fatigue and sleep problems. CONCLUSIONS: PI is an important mediator in the relationship of pain on fatigue and sleep, while PC is a mediator on fatigue after cancer treatment. These findings highlight that both appraisals are understudied and open new perspectives regarding treatment strategies in BCS.

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.

Do Sex and Pain Characteristics Influence the Effectiveness of Pain Neuroscience Education in People Scheduled for Total Knee Arthroplasty? Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: This explorative study investigates the moderating effect of sex and baseline pain characteristics on the effectiveness of preoperative pain neuroscience education (PNE) plus knee joint mobilization versus biomedical education plus knee joint mobilization in patients who have knee osteoarthritis and are scheduled to undergo total knee arthroplasty (TKA). METHODS: After baseline assessment of self-reported questionnaires (pain intensity, disability, symptoms of central sensitization and pain cognitions) and quantitative sensory testing, 44 participants with knee osteoarthritis were randomized into the PNE plus knee joint mobilization or biomedical education plus knee joint mobilization group. The questionnaires were retaken directly after and 1 month after 4 sessions of treatment and at 3 months after surgery. Based on baseline quantitative sensory testing results, the sample was subdivided into a high (showing high experimental pain levels and low pressure pain thresholds) and low pain cluster using principal components analysis and cluster analysis. Therapy effects over time were evaluated using 3-way analysis of variance, with time as the within factor and treatment, sex, and baseline pain cluster as between factors. RESULTS: Women benefited significantly more from the PNE intervention compared with the control intervention in terms of self-reported symptoms of central sensitization. For both pain clusters, differences in therapeutic effects concerning pain intensity and pain cognitions were found, with higher superiority of the PNE intervention in the high-pain cluster subgroup compared with the low-pain cluster. CONCLUSION: Based on these explorative analyses, it can be concluded that sex and preoperative pain measures may influence the effectiveness of preoperative PNE for some specific outcome measures in people scheduled to undergo TKA. IMPACT: Although further research on this topic is needed, the potential influence of sex and preoperative pain measures on the effectiveness of preoperative PNE should be considered when implementing this intervention in people undergoing TKA.

Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future.

Recently, the International Association for the Study of Pain (IASP) released clinical criteria and a grading system for nociplastic pain affecting the musculoskeletal system. These criteria replaced the 2014 clinical criteria for predominant central sensitization (CS) pain and accounted for clinicians' need to identify (early) and correctly classify patients having chronic pain according to the pain phenotype. Still, clinicians and researchers can become confused by the multitude of terms and the variety of clinical criteria available. Therefore, this paper aims at (1) providing an overview of what preceded the IASP criteria for nociplastic pain ('the past'); (2) explaining the new IASP criteria for nociplastic pain in comparison with the 2014 clinical criteria for predominant CS pain ('the present'); and (3) highlighting key areas for future implementation and research work in this area ('the future'). It is explained that the 2021 IASP clinical criteria for nociplastic pain are in line with the 2014 clinical criteria for predominant CS pain but are more robust, comprehensive, better developed and hold more potential. Therefore, the 2021 IASP clinical criteria for nociplastic pain are important steps towards precision pain medicine, yet studies examining the clinimetric and psychometric properties of the criteria are urgently needed.

Pain and Opioid Use in Cancer Survivors: A Practical Guide to Account for Perceived Injustice.

BACKGROUND: The presence of pain decreases survival rates in cancer. Pain management in clinical settings is often suboptimal and secondary to other cancer-related treatments, leaving many people undertreated. Opioid use is associated with side effects and decreased survival rate in cancer patients. Hence, there is an urgent need for considering factors such as perceived injustice that sustain post-cancer pain and trigger a behavioral pattern associated with opioid use. Injustice beliefs represent a maladaptive pattern of cognitive appraisal that may be a salient target for improving pain-related coping in these patients. Perceived injustice is associated with increased opioid prescription and prospectively predicted opioid use at 1-year follow-up, urging the need for targeted interventions to diminish perceived injustice. OBJECTIVES: Explain the importance of screening for perceived injustice in patients with pain following cancer treatment, its potential relevance for opioid abuse, and its potential impact on the management of pain following cancer. Also, prove clinicians with a clinical guide for an approach comprising of modified pain neuroscience education, motivational interviewing, and acceptance-based interventions to account for perceived injustice in patients having pain following cancer. STUDY DESIGN: A narrative review, perspective and treatment manual. SETTING: Several universities, a university of applied science department, a university hospital, and a private clinic (i.e., transdisciplinary pain treatment center). METHODS: Patients were cancer survivors with pain. Intervention included modified pain neuroscience education, motivational interviewing, and acceptance-based interventions. Measurements were taken through the Injustice Experience Questionnaire (IEQ). RESULTS: The IEQ can be used to assess perceived injustice in a valid way. Education about pain, including discussing perceived injustice, should be the first part of the management of pain in cancer survivors. In order to obtain the often-required behavioral change towards a more adaptive lifestyle, motivational interviewing can be used. To thoroughly tackle perceived injustice in patients having pain following cancer, special emphasis should be given to the individual reasons patients identify for experiencing (continued) pain and related symptoms. Pain acceptance should also be thoroughly addressed. LIMITATIONS: Clinical trials exploring the benefits, including cost-effectiveness, of such a multimodal approach in patients with pain following cancer treatment are needed. CONCLUSIONS: In light of its potential relevance for opioid abuse and potential impact on conservative management strategies, clinicians are advised to screen for perceived injustice in patients with pain following cancer treatment. Therapeutic targeting of perceived injustice can be done through an approach comprising of modified pain neuroscience education, motivational interviewing, and acceptance-based interventions.

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.

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.