Targeting Pain Science Education in Youth With Chronic Pain: What Are the Sticking Points for Youth and Their Parents?

OBJECTIVES: An important part of providing pain science education is to first assess baseline knowledge and beliefs about pain, thereby identifying misconceptions and establishing individually-tailored learning objectives. The Concept of Pain Inventory (COPI) was developed to support this need. This study aimed to characterize the concept of pain in care-seeking youth and their parents, to examine its clinical and demographic correlates, and to identify conceptual gaps. MATERIALS AND METHODS: Following an initial interdisciplinary evaluation, a cohort of 127 youth aged 8 to 18 years, and their parents, completed a series of questionnaires. RESULTS: Parents had slightly higher COPI scores than youth did, reflecting parents' greater alignment with contemporary pain science. The moderate positive association with older age among youth ( r =.32) suggests that COPI is sensitive to cognitive development and life experiences. Youth and parent COPI responses were weakly associated ( r =0.24), highlighting the importance of targeting the concept of pain in both groups. For both parents and youth, 'Learning about pain can help you feel less pain' was the least endorsed concept. This conceptual 'gap' is a key point of intervention that could potentially lead to greater engagement with multidisciplinary pain treatment. DISCUSSION: The COPI appears useful for identifying conceptual gaps or 'sticking points'; this may be an important step to pre-emptively address misconceptions about pain through pain science education. Future research should determine the utility of COPI in assessing and treating youth seeking care for pain. The COPI may be a useful tool for tailoring pain science education to youth and their parents.

Assessing the Reconceptualization of Pain in Graduate-Entry Physiotherapy Students Using the Concept of Pain Inventory for Adults: The University of Technology Sydney Physiotherapy Student Surveys Project.

INTRODUCTION: Validly and reliably assessing conceptual change is essential for evaluating the effectiveness of pain science education for physiotherapy students. We aimed to 1) evaluate concept of pain before and after a 14-week pain science education university subject, 2) assess structural validity of the Concept of Pain Inventory for Adults (COPI-Adult) in postgraduate entry-level physiotherapy students, and 3) explore possible relationships between baseline variables and baseline COPI-Adult scores. REVIEW OF LITERATURE: As the COPI-Adult is a newly developed questionnaire, there is a lack of data regarding its psychometric properties. SUBJECTS: Of 129 enrolled students at an Australian university, 124 (96%) and 114 (88%) completed the baseline and follow-up questionnaires, respectively. METHODS: In this prospective cohort study, students who commenced the degree in 2020 or 2021 completed online questionnaires, including the COPI-Adult, at the start and end of their first semester. This semester included a 14-week pain science education subject and other physiotherapy-related subjects. Higher COPI-Adult scores (range = 0-52) indicate better alignment with contemporary pain science. We 1) compared differences in concept of pain before and after the semester, 2) performed a confirmatory factor analysis on the COPI-Adult, and 3) performed exploratory regression analyses. RESULTS: Concept of Pain Inventory for Adults scores increased from baseline (median [interquartile range]: 39 [36-44]) to follow-up (48 [44-51]). The COPI-Adult retained its 1-factor structure, with acceptable internal consistency (Cronbach's alpha = 0.80). Exploratory analysis showed that previously completing a subject on pain was related to higher COPI-Adult baseline scores. Age, gender, and mental health diagnosis did not relate to baseline COPI-Adult scores. DISCUSSION AND CONCLUSION: Following a 14-week pain science education subject embedded within a physiotherapy degree, students improved their concept of pain. The COPI-Adult maintains a 1-factor structure in this population. Completing a previous subject on pain was associated with higher COPI-Adult scores.

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain.

INTRODUCTION: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches. METHODS AND ANALYSIS: Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function. ETHICS AND DISSEMINATION: The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories. TRIAL REGISTRATION NUMBER: NCT04285112.

A hormonal therapy for menopausal women with MS: A phase Ib/IIa randomized controlled trial.

INTRODUCTION: Most women develop MS before menopause. Menopausal hot flashes can worsen MS symptoms, and could be relieved with hormone therapy. Our objective was to evaluate feasibility, tolerability and symptom response of Duavee® (bazedoxifene + conjugated estrogen) in a Phase Ib/IIa double-blind randomized controlled clinical trial. METHODS: We randomized 24 peri/postmenopausal women with MS and symptomatic hot flashes 1:1 to Duavee® versus placebo. Evaluations occurred at baseline and 2 months. RESULTS: Groups were balanced for age (mean 51.2 ± 3.6 years), EDSS [median 3 (IQR:2.5, 4.5)], and MS duration. 21/24 participants completed the study. FEASIBILITY: Enrollment was protracted (34 months), partially due to concerns about hormone therapy safety. TOLERABILITY: treatment group participants reported greater satisfaction and fewer missed doses; one participant (placebo) developed new MRI lesions; liver function testing remained normal for all patients. SYMPTOMS: Hot Flash Related Daily Interference scale at 2 months was lower in treatment vs. placebo group [median (IQR) of 4 (0.5, 14) vs. 9 (0, 33)]. Between-group differences were not statistically significant. CONCLUSION: Despite perceived benefits in MS, estrogens have perceived risks that represent a hurdle to enrollment. With appropriate education and screening of participants, the favorable study retention (87%) and treatment satisfaction observed in the current study support the feasibility of a longer, powered trial to evaluate whether a proven treatment for menopausal symptoms, Duavee®, could also improve MS-related function in menopausal women with MS.

Amygdala functional connectivity mediates the association between catastrophizing and threat-safety learning in youth with chronic pain.

ABSTRACT: There is a need to identify brain connectivity alterations predictive of transdiagnostic processes that may confer vulnerability for affective symptomology. Here, we tested whether amygdala resting-state functional connectivity (rsFC) mediated the relationship between catastrophizing (negative threat appraisals and predicting poorer functioning) and altered threat-safety discrimination learning (critical to flexibly adapt to new and changing environments) in adolescents with persistent pain. We examined amygdala rsFC in 46 youth with chronic pain and 29 healthy peers (age M = 15.8, SD = 2.9; 64 females) and its relationship with catastrophizing and threat-safety learning. We used a developmentally appropriate threat-safety learning paradigm and performed amygdala seed-based rsFC and whole-brain mediation analyses. Patients exhibited enhanced connectivity between the left amygdala and right supramarginal gyrus (SMG) (cluster-level P-FDR < 0.05), whereas right amygdala rsFC showed no group differences. Only in patients, elevated catastrophizing was associated with facilitated threat-safety learning (CS+>CS-; rp = 0.49, P = 0.001). Furthermore, in patients, elevated catastrophizing was associated with reduced left amygdala connectivity with SMG / parietal operculum, and increased left amygdala connectivity with hippocampus, dorsal striatum, paracingulate, and motor regions (P < 0.001). In addition, blunted left amygdala rsFC with right SMG/parietal operculum mediated the association between catastrophizing and threat-safety learning (P < 0.001). To conclude, rsFC between the left amygdala (a core emotion hub) and inferior parietal lobe (involved in appraisal and integration of bodily signals and attentional reorienting) explains associations between daily-life relevant catastrophizing and threat-safety learning. Findings provide a putative model for understanding pathophysiology involved in core psychological processes that cut across diagnoses, including disabling pain, and are relevant for their etiology.

The Concept of Pain Inventory for Adults (COPI-Adult): Assessing Knowledge and Beliefs Regarding Pain Science Education.

OBJECTIVES: Assessing knowledge and beliefs regarding pain science can identify gaps and misconceptions. The Concept of Pain Inventory (COPI) was recently developed in children with the intent to guide targeted pain science education. We utilized the original COPI item pool to (1) develop a tool to assess an adult's concept of pain in a cohort who had not received pain science education, (2) evaluate its psychometric properties, (3) examine distribution of scores in a cohort of adults who had received pain science education, and (4) examine associations between scores and clinical variables. MATERIALS AND METHODS: A total cohort of 627 adults were recruited through social media for an online survey. Initial development was conducted on those who had not received prior pain science education (n=125), then the COPI-Adult tool was tested in those who had received prior pain science education (n=502). RESULTS: The resulting unidimensional 13-item COPI-Adult had acceptable internal consistency (α=0.78) and good test-retest reliability at 1 week (Intraclass Correlation Coefficient3,1=0.84 (95% confidence interval: 0.71-0.91). Higher COPI-Adult scores reflect greater alignment with contemporary pain science. COPI-Adult scores were correlated with revised Neurophysiology of Pain Questionnaire (rNPQ) scores and inversely correlated with average and current pain intensity, and pain interference. Adults who reported having received pain science education had significantly higher mean COPI-Adult scores than those who had not, and this difference exceeded the smallest detectable change. DISCUSSION: The COPI-Adult is a brief questionnaire with promising psychometric properties to identify conceptual gaps or misconceptions to inform individualized pain science education.

Experiences of sexual and gender minority people living with multiple sclerosis in Northern California: An exploratory study.

BACKGROUND: Sexual and gender minority (SGM) individuals may face unique challenges in accessing quality medical care due to structural disparities, social discrimination, and lack of culturally competent healthcare. Multiple sclerosis (MS) requires complex care. Little research has been carried out at the intersection between SGM identity and MS care. OBJECTIVE: To identify unmet clinical and social needs in our clinical population of SGM patients with MS. METHODS: Patients with MS who self-identified as SGM were recruited through the UCSF MS Center and a National MS Society web post to complete a 45-minute web-based (Qualtrics) survey. The mixed qualitative and quantitative survey covered experiences with different domains of MS care, drug/alcohol use, relationship status, social support, and participation in MS and SGM communities. RESULTS: Among the 26 survey respondents, mean age was 50.2 (SD 10.6) years; gender identity was women (46%) men (38%) and genderqueer, transgender, or other (15%); sexual orientation was gay/lesbian/bisexual (35%), pansexual/queer (27%), questioning (23%), or other identity (15%). Over two thirds (69%) of respondents were partnered. Overall satisfaction with MS care was high: 79.2% participants scored ≥4/5 (somewhat or extremely satisfied); participants dissatisfied with their care cited feeling dismissed. While 87.5% felt that their SGM identities did not affect their MS care, still 30% did report feeling uncomfortable discussing their SGM identities with their clinician. Participants rated low impact of having MS on participation in SGM communities (mean 2.4/5 on Likert scale); those participants reporting higher impact cited fatigue, immobility and stigmatization of disease as primary factors. Similarly, SGM status had low effect on participation in the MS community (mean 1.4/5); higher impact was related to apprehension around identity disclosure to new groups. Identified resources that might improve MS care included more representation, inclusivity and openness from clinicians, and SGM-focused MS support groups. DISCUSSION: In this exploratory survey of the needs of SGM people living with MS in Northern California, most participants reported that they were unlikely to participate in activities in the SGM community due to MS status or symptoms, however most felt that their SGM status did not affect their MS care. Given the center's location in a hub for SGM community and activism, surveying individuals in other settings would provide greater insights into the role of community, clinical support and the experience of SGM people living with MS.

Something Else Going On? Diagnostic Uncertainty in Children with Chronic Pain and Their Parents.

Diagnostic uncertainty, the perceived lack of an accurate explanation of the patient's health problem, remains relatively unstudied in children. This study examined the prevalence, familial concordance, and correlates of diagnostic uncertainty in children and their parents presenting to a multidisciplinary pain clinic in the United States. One hundred and twenty-six parents and 91 of their children (Mage = 13.93 years, range = 8-18 years) completed a brief three-item measure of diagnostic uncertainty, as well as measures of pain-related distress and functioning. Forty-eight percent of children and 37% of parents believed something else was going on with the child's pain that doctors had not found out about yet. Across the three items, 66%-77% of children and their parents agreed in their endorsement of diagnostic uncertainty. Parents who believed that something else was going on with their child's pain had children with higher avoidance of pain-related activities (F = 5.601, p = 0.020) and lower pain willingness (F = 4.782, p = 0.032). Neither parent nor child diagnostic uncertainty was significantly related to the child's pain-related functioning. Diagnostic uncertainty, particularly in parents, is relevant in the experience of pediatric chronic pain and warrants further investigation as both a risk factor and therapeutic target.

mHealth for pediatric chronic pain: state of the art and future directions.

INTRODUCTION: Chronic pain conditions are common among children and engender cascading effects across social, emotional, and behavioral domains for the child and family. Mobile health (mHealth) describes the practice of delivering healthcare via mobile devices and may be an ideal solution to increase access and reach of evidence-based behavioral health interventions. AREAS COVERED: The aim of this narrative review is to present a state-of-the-art overview of evidence-based mHealth efforts within the field of pediatric chronic pain and consider new and promising directions for study. Given the nascent nature of the field, published mHealth interventions in all stages of development are discussed. Literature was identified through a non-systematic search in PubMed and Google Scholar, and a review of reference lists of papers that were identified as particularly relevant or foundational (within and outside of the chronic pain literature). EXPERT OPINION: mHealth is a promising interventional modality with early evidence suggesting it is primed to enhance behavioral health delivery and patient outcomes. There are many exciting future directions to be explored including drawing inspiration from digital health technology to generate new ways of thinking about the optimal treatment of pediatric chronic pain.

Silent progression in disease activity-free relapsing multiple sclerosis.

OBJECTIVE: Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow-up. Notably, "no evidence of disease activity" at 2 years did not predict long-term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long-term disability accumulation. METHODS: Disability progression was defined as an increase in Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 (or greater) from baseline EDSS = 0, 1.0-5.0, and 5.5 or higher, respectively, assessed from baseline to year 5 (±1 year) and sustained to year 10 (±1 year). Longitudinal analysis of relative brain volume loss used a linear mixed model with sex, age, disease duration, and HLA-DRB1*15:01 as covariates. RESULTS: Relapses were associated with a transient increase in disability over 1-year intervals (p = 0.012) but not with confirmed disability progression (p = 0.551). Relative brain volume declined at a greater rate among individuals with disability progression compared to those who remained stable (p < 0.05). INTERPRETATION: Long-term worsening is common in relapsing MS patients, is largely independent of relapse activity, and is associated with accelerated brain atrophy. We propose the term silent progression to describe the insidious disability that accrues in many patients who satisfy traditional criteria for relapsing-remitting MS. Ann Neurol 2019;85:653-666.

A Videogame-Based Digital Therapeutic to Improve Processing Speed in People with Multiple Sclerosis: A Feasibility Study.

INTRODUCTION: Self-administered in-home digital therapeutics could expand access to cognitive rehabilitation for individuals with multiple sclerosis (MS), over half of whom experience cognitive impairment (CI). However, feasibility in an MS population must be clarified. This study was conducted to assess the feasibility of deploying a videogame-like digital treatment for CI in MS, including initial efficacy and barriers to adherence. METHODS: In this pilot study, 21 participants with MS completed an in-clinic baseline neurological evaluation. Cognitive tests included paper-and-pencil Brief International Cognitive Assessment for Multiple Sclerosis [BICAMS-which included the Symbol Digit Modalities Test (SDMT)] and other unsupervised tablet-based tests (including Match: an unsupervised test of executive functions and processing speed, developed at UCSF; and the Cogstate MS Battery). Participants then completed an in-home, tablet-based, videogame-like investigational digital treatment (Project: EVO™) for 25 min daily, 5 days weekly, for 4 weeks. This was followed by a repeat in-clinic evaluation. RESULTS: Of the 21 participants (mean [standard deviation, SD] age 53.8 [11.6] years, median Expanded Disability Status Scale (EDSS) 2.5 [SD 2.0, IQR [2-3.5]]) enrolled to use the digital therapeutic at home (mean [SD] SDMT z score: - 0.21 [1.16]), 18 completed the study, during which they completed an average of 19.7 days (median [SD]: 20.5 [8.4]). Overall, 78% of these 18 participants completed 75% of prescribed days (i.e., at least 15), and 50% completed all 20 days or more. Over the 4-week period, scores of processing speed improved significantly (based on one-sided t test), including SDMT (p = 0.003) and Match (p = 0.006). The Cogstate DET test (psychomotor function) also increased (p = 0.006). Mean increase in SDMT was 3.6 points. Male sex, not being employed, and higher baseline anxiety all were significantly associated with greater improvement in SDMT over the 4-week period. Interestingly, lower baseline cognitive scores were associated with greater number of sessions completed (e.g., SDMT: p = 0.003, R2 = 0.44). Adjusting for employment, a proxy for time available, did not significantly improve the model fit. DISCUSSION: Deploying an in-home digital tool to improve processing speed in MS is feasible, and shows preliminary efficacy. A larger, randomized controlled clinical trial is ongoing.