Carol M. Greco

Background: Chronic low back pain (cLBP) is a prevalent and debilitating condition. Gaining insight into the daily experiences of those with cLBP is crucial for developing effective management. Pain and activity are typically assessed at a single time point and often rely on retrospective self‐reports, which can be prone to recall bias and may not reflect the day‐to‐day variability of these experiences. As a part of the University of Pittsburgh LB ³ P Mechanistic Research Center, this study used ecological momentary assessment (EMA) and wearable devices to collect real‐time data in a large cohort of adults with cLBP. The primary aims were to collect and characterize pain and activity profiles of individuals with cLBP. Methods: This study enrolled 1007 adults with cLBP who met the National Institutes of Health defined criteria. Over 7 days, participants were assessed in their own environment. EMA was gathered in real‐time via a custom mobile app, prompting participants three times daily to provide their perceptions of current pain intensity (0–10), pain interference (0–10), and activity level (very light to vigorous). Time of falling asleep and waking was also reported. Participants wore ActiGraph GT9X devices on their wrist and waist. A custom back sensor was also adhered to the skin over the lumbar (L5) segment. Activity counts, wear time, and step counts were calculated, utilizing algorithms provided by ActiGraph. Sensor data were filtered to include at least 4 days of 10 or more hours each. Activity counts were categorized into sedentary, light, and moderate‐to‐very‐vigorous based on Freedson Adult cutpoints. Results: Out of 1007 participants, 989 submitted EMA data (58.8 ± 16.5 years old; 40% male and 60% female; mean pain intensity at enrollment of 5.4 (SD 2.1) and a median of 5 (interquartile range [IQR] 3) on a 0–10 scale; mean PROMIS Pain Interference T ‐score at enrollment of 60.5 (SD 7.5) and a median of 61.2 (IQR 9.6)). The median reported pain intensity level from the EMA was 1 (IQR = 3), while pain interference was 3 (IQR = 3). More than half of the participants reported a median pain intensity of either 0 or 1 (54.0%) and a median pain interference between 0 and 3 (57.4%). Most participants self‐reported their activity levels as moderate (36%) or light (33%). Based on pain ratings during each day, most participants had their pain intensity (30%) and pain interference (40%) peaking in the evening. ActiGraph data from 884 wrist‐worn and 785 waist‐worn devices were analyzed. Wrist data showed a median of 1 765 325 (IQR 796 995) activity counts/day and 9575 (IQR 4228) steps/day. Waist data showed 358 390 (IQR 223 758) activity counts/day and 4114 (IQR 3146) steps/day. The percentage of daily sedentary activity was 47.3% for wrist and 72.8% for waist. The back sensor data from 586 participants showed a median of 340 345 (IQR = 223 399) activity counts/day and a median of 3695 (IQR = 2743) steps/day. The percentage of time spent in daily sedentary activity was 82.6%. Both ActiGraph devices and the back sensor indicated that the majority of the time was spent in sedentary activity level, which is lower than the activity level reported in the EMA. Conclusions: Despite having cLBP with self‐reported moderate pain levels, participants generally reported periods of relatively low levels of pain intensity and interference in their EMA. In addition, their EMA‐reported activity levels differed from the sensor data. Participants self‐reported higher levels of activity compared to the activity levels calculated by the wearable sensors. This suggests that participants overestimated their activity levels on EMA, or that the activity level cut‐points may need to be re‐evaluated for the cLBP population. Additionally, sensors placed on different body locations showed varying activity and step counts. The activity counts calculated from the waist ActiGraph and the back sensor from this cohort were lower than the average activity counts in the US adult population. Further research is needed to better quantify these differences for people with cLBP to develop a more comprehensive understanding of the pain experience.

Background: Chronic low back pain (cLBP) requires precise phenotyping for tailored treatments. This study introduces a mobile health (mHealth) system for cLBP assessment, aiming to collect extensive biomechanical and behavioral data from in‐clinic and seven‐day at‐home assessments from 1000 individuals with cLBP to accommodate accurate phenotyping. Methods: Using a user‐centered design approach, an integrated mHealth system was developed, comprising two mobile applications: a clinician‐facing in‐clinic app and a participant‐facing at‐home app. The in‐clinic app aids physical therapists in conducting in‐clinic assessments, while the at‐home app allows cLBP patients to manage and submit responses to ecological momentary assessments (EMA). Usability evaluations were conducted using the mHealth App Usability Questionnaire (MAUQ) and qualitative open‐ended questions asking about ease of use, learnability, overall impression and satisfaction, and reflective questions. Scores from MAUQ were summarized using median and interquartile range (IQR). The usability results were used to iteratively refine the system's design and functionality. Results: Three physical therapists and 337 out of 522 cLBP patients participated in the usability evaluations. The evaluations demonstrated positive feedback for both apps. For the in‐clinic app, the first iteration median MAUQ score was 6 (IQR 1) and the second iteration median MAUQ score was also 6 (IQR 2). For the at‐home app, the median MAUQ scores were consistently high across five iterations (median score of 7 (IQR 1) for all iterations). These scores indicated good usability, meaning they were easy to use, efficient, and satisfying. Iterative modifications based on the feedback focused on enhancing navigation consistency, responsiveness, and user interface, resulting in overall improved usability. Conclusion: The in‐clinic app was successfully used by physical therapists for the assessments of 1000 cLBP patients, receiving positive feedback. Similarly, 989 cLBP patients used the at‐home app to complete and submit their EMA, finding it easier to comply with the assessment.

Background: Chronic low back pain (cLBP) is a multifactorial condition that can have various contributing factors, including biological, biomechanical, and behavioral. Recent evidence suggests that systemic inflammation may contribute to cLBP, impacting pain sensitivity and individuals' functional status. Circulatory pro‐ and anti‐inflammatory cytokines are widely used to determine individuals' systemic inflammatory status. The University of Pittsburgh Mechanistic Research Center, part of the National Institutes of Health's (NIH) Helping to End Addiction Long‐term Initiative, conducted a prospective, observational study to identify phenotypes in a large cohort of individuals with cLBP. The present work reports the quantification of key circulatory cytokines in this cLBP cohort. Methods: A total of 1007 individuals with cLBP were enrolled. Plasma samples were available from 936 participants, and concentrations of pro‐inflammatory (IL‐6, IFN‐γ, TNF, IL‐15, Leptin) and anti‐inflammatory (IL‐1ra, IL‐10) cytokines were measured via immunoassays. Pain and functional status were assessed using validated self‐reported numeric pain ratings scale and the Oswestry Disability Index. Descriptive statistics of analyzed cytokines were reported across the overall population, stratified by age (< 60 and ≥ 60 years old) and sex, and by pain levels as mild (0–5), moderate (6, 7), and severe (8–10), and ODI, categorized as minimal disability (0%–20%), moderate (21%–40%), and severe disability (> 40%). Results: The values of circulating cytokines assessed in this study aligned with those reported in the literature for other painful inflammatory conditions and, in most cases, exceeded those documented for healthy populations. IL‐6, IL‐1ra, and Leptin demonstrated higher concentrations with higher pain and disability severity. TNF showed higher concentration in participants with higher disability severity. Concentration levels of IFN‐γ, IL‐15, and IL‐10 exhibited no differences across pain or ODI categories. Notably, TNF levels were higher in older adults (≥ 60 years), whereas Leptin levels were higher in females than in males. Conclusion: This study provides a snapshot of key circulating cytokines in a large cLBP cohort, revealing differences in pro‐ and anti‐inflammatory cytokines across pain and disability for the overall population and in sex and age subgroups. Additional longitudinal and mechanistic studies are required to clarify how cytokines could serve as diagnostic, prognostic, or phenotyping markers, ultimately informing targeted, inflammation‐focused therapies that may reshape current treatment approaches.

Background: Chronic low back pain (cLBP) is extremely common and is one of the Chronic Overlapping Pain Conditions (COPCs), 10 conditions thought to have similar underlying pathophysiology. Little is known about the prevalence and co‐occurrence of cLBP with other commonly accepted conditions referred to as COPCs. Methods: We assessed participants enrolled in a pragmatic trial of mindfulness‐based stress reduction for cLBP to determine the prevalence of co‐occurring COPCs using a validated COPC screener. We compared psychosocial and physical functioning among participants with only cLBP and participants with cLBP and additional COPCs using Student's t ‐tests, chi‐squared tests and multivariable linear regression. Results: Among 285 enrollees (age range: 18–88 years, mean age: 52.2 years, SD = 15.3), 272 (95%) reported pain outside the upper and lower back region. One hundred and twenty‐nine people (45%) had one COPC, and 68 (24%) had two or more COPCs not including cLBP. The most common COPCs were irritable bowel syndrome ( n = 56, 20%); myalgia encephalomyelitis/chronic fatigue syndrome ( n = 54, 19%); and fibromyalgia ( n = 42, 15%). Conclusion: We found strong differences when comparing people with cLBP alone to those with cLBP and COPCs. People with COPCs reported more pain symptoms, higher levels of anxiety, depression, fatigue and scored worse across measures of physical functioning and pain symptoms. An additional COPC was associated with a 7.6‐point increase in fatigue scores (95% CI: 5.6, 9.7) on a T‐score metric (mean = 50, SD = 10). Significance Statement: Compared to people with low back pain alone, individuals with additional chronic pain experienced more severe pain symptoms, more anxiety, depression and fatigue. In this sample of people with cLBP, overlapping pain conditions were common, affecting 45% of people. Registration Number and Registry Name: Clinicaltrials.gov identifier NCT04129450.

Background: Quantitative Sensory Testing (QST), also known as psychophysical testing, includes standardized methods for assessing humans' perceptions of different types of sensory stimuli and their associated pain thresholds. QST results can be used to estimate altered or atypical sensory processing and thus can be useful for determining pain mechanisms such as nociplastic or central nervous system‐mediated pain. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB ³ P),” is part of the National Institutes of Health's Helping to End Addiction Long‐term Initiative. LB ³ P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. QST was conducted on these participants as part of comprehensive data collection. This article reports on the results of the QST procedures performed at the initial in‐person enrollment visit. Methods: Four QST procedures were administered to participants of the LB ³ P study at their enrollment visit: (1) Pressure Pain Thresholds (PPT) over the participant‐reported site of lumbar pain (paraspinals) and a control site (trapezius) using an analog algometer; (2) Temporal Summation (TS) over the lumbar pain and control sites (forearm) using a Neuropen with a 40‐g monofilament; (3) Conditioned Pain Modulation (CPM) using a cold water (5°C) immersion tank; and (4) Cold Water Tolerance time. A subset of LB ³ P participants was excluded from the CPM and cold‐water immersion procedures due to medical comorbidities such as cardiovascular disease and diabetic neuropathy. Means and standard deviations (SDs) were calculated from three trials of PPT and TS, two trials of CPM, and one trial of cold‐water immersion time. TS was calculated by subtracting the numeric pain scores (0–10 scale) of the first from the 10th pinpricks. CPM was calculated by subtracting the mean trapezius algometer readings during the PPT procedure from those of the trapezius PPT during cold‐water immersion. Results: The final cohort of QST participants was 999 adults. The mean/SD of lumbar and trapezius PPTs was 4.6 (2.4) and 4.4 (1.9) kg/cm ² , respectively. The mean/SD of lumbar and forearm TS was 1.6 (2.0) and 1.2 (1.8). Lingering pain after the 10th pinprick (after‐sensations) was reported by 19.3% and 15.6% of participants after a series of 10 pinpricks was applied to the lumbar pain site and control site, respectively. The mean/SD CPM was 0.9 (1.2) with a wide range of CPM values from −2.9 to 5.9. The cold‐water tolerance test resulted in a bimodal distribution, with 83% of participants having an average immersion time of 30 s and the remaining 17% reaching the maximum immersion time of 180 s. Conclusions: QST data were collected from a large cohort of individuals with cLBP who participated in the LB ³ P observational study. The QST results provide reference values for persons living with cLBP.

Background: Chronic low back pain (cLBP) is complex, disabling, and costly to patients and to society. Patients' social circumstances, beliefs, and behaviors interact in a dynamic way with biomedical factors and have the potential to amplify or reduce suffering. It is important to assess the experience of pain via patient‐reported outcomes (PROs). The University of Pittsburgh Mechanistic Research Center, entitled, “ Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB ³ P),” is part of the National Institutes of Health's Helping to End Addiction Long‐term Initiative. LB ³ P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. This article reports key information from the PROs and selected demographic variables obtained at the in‐person LB ³ P study enrollment visit. Methods: The LB ³ P study participants completed numerous PROs, including the minimum data set assessments of the NIH Research Task Force on back pain and the NIH HEAL Initiative's Common Data Elements. PROs were organized into five conceptual domains: (1) Pain Characteristics and Qualities, (2) Pain‐related Psychosocial Factors, (3) General Psychosocial Factors, (4) General Health and Lifestyle Factors, and (5) Social Determinants of Health (SDoH). Patient Acceptance of Symptom Status, which consists of yes/no responses to 10 questions about whether the level of each of the 10 symptoms is satisfactory, was also assessed. Results: PRO measures were collected from 1007 LB ³ P participants with cLBP. The means and standard deviations, or medians and interquartile ranges, and percentages for the PRO variables collected at the in‐person enrollment visit are presented for the overall group and stratified by sex at birth (females and males) and by age (< 60 years old and ≥ 60 years old). For the participants overall, and across sex and age groups, pain intensity and interference were moderate on average. Neuropathic pain, assessed via PainDETECT, was present in 18% of the overall sample, and in 22.5% of those younger than 60. On average, fatigue, depressive and anxiety symptoms, memory and concentration, self‐efficacy, and positive outlook were within normal limits, as indicated by PROMIS T‐scores. However, PROMIS Physical function was below normal, with T‐scores in the mild to moderate range of impairment. When participants were asked to rate the acceptability of their symptom status in 10 areas of function, the most frequently reported areas of dissatisfaction were: pain intensity and interference, physical function, sleep, and fatigue. In the area of SDoH, nearly half (44%) of participants reported having been exposed to traumatic experiences. In the overall group, 36% reported difficulty paying for basic needs such as food, medical care, and heating, while 51% of those in the < 60 group reported this level of financial strain. Conclusions: The LB ³ P cLBP observational cohort exhibited moderate levels of pain intensity, pain interference with life activities, and pain‐related disability. Participants reported mild to moderate levels of pain‐related psychosocial factors, and general mental health challenges such as depression and anxiety were relatively rare. Many participants reported a history of exposure to traumatic experiences and having current financial challenges. The LB ³ P PRO results provide reference values for a community sample of persons with cLBP.

This article has been temporarily removed for administrative purposes.

Objective: Chronic low back pain (cLBP) is a significant public health problem in the United States. A method to identify treatments that are most likely effective for an individual patient based on their unique characteristics is needed. Methods: The Biomarkers for Evaluating Spine Treatments (BEST) Trial is a sequential, multiple assignment, randomized trial designed to estimate an optimal treatment or combination of treatments to reduce pain intensity and interference at 24 weeks in individuals with cLBP. Results: We describe the patient-reported characteristics of the BEST Trial at the Baseline visit. Data collection for extensive required phenotyping is reported. We analyzed the run-in period of the BEST Trial to evaluate predictors of run-in failure. The BEST Trial enrolled 1019 participants and randomized 805 participants (61.6% female, mean age 50.4, 12.5% Black or African American) to the first stage of treatment. We collected extensive required phenotyping on all 805 randomized BEST Trial participants, and additional optional phenotyping on 510 (63.4%) participants. Conclusions: The BEST Trial successfully enrolled a racially and geographically diverse sample of chronic low back pain patients and completed rich phenotypic assessments to inform our primary goal of identifying in whom different treatments show optimal response. We demonstrated the feasibility of collecting extensive phenotypic assessments in a multi-site clinical trial of cLBP. Clinical trial registration number: The Biomarkers for Evaluating Spine Treatments (BEST) Trial is registered on ClinicalTrials.gov. Registration number: NCT05396014 (https://clinicaltrials.gov/study/NCT05396014).

Importance: Chronic low back pain (cLBP) is associated with reduced gait speed and other gait quality impairments. Fear-avoidance and pain catastrophizing impact movement in cLBP, but their specific impact on gait quality is unknown. Objective: This study aimed to determine associations between fear-avoidance or pain catastrophizing and gait quality in cLBP. Design: This was a cross-sectional study. Setting: This study occurred at a university. Participants: There were 500 individuals (56.6 [SD = 16.5] years old; 311 female) with cLBP. Interventions: Participants completed the Fear-Avoidance Beliefs Questionnaire – Physical Activity (FABQ-PA) and 6-item Pain Catastrophizing Scale. Participants were divided into high and low fear-avoidance subgroups based on an established FABQ-PA cutoff (>14). Main Outcomes and Measures: Gait speed was measured during a 4-meter walk test, while step time average, step time variability, and symmetry were derived from a lumbar inertial measurement unit worn during a 2-minute walk test. Multiple linear regression models were used to determine relationships between fear-avoidance or pain catastrophizing and gait quality. T tests were used to determine gait quality differences between high versus low fear-avoidance subgroups. Results: High fear-avoidance was associated with reduced gait speed (B = −0.0039), but pain catastrophizing was not. The high fear-avoidance subgroup had slower gait speed (mean difference = 0.05 m/s), longer step time (mean difference = 0.02 s), and higher step time variability (mean difference = 0.004 s) compared to the low fear-avoidance subgroup. Conclusions: Fear-avoidance is associated with slower gait speeds, even after adjusting for demographics, pain, and disability. The established FABQ-PA cutoff is robust in detecting gait differences between high versus low fear-avoidance subgroups. Relevance: It may be important to consider fear-avoidance in the delivery of multi-modal interventions to address gait impairments. Future studies are needed to determine the impact of addressing fear-avoidance alongside traditional gait interventions in cLBP.

Background: The chronic low back pain (cLBP) literature rarely includes comprehensive characterization of demographic and biomedical factors in a large sample of individuals. The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB ³ P),” is part of the National Institutes of Health's Helping to End Addiction Long‐term Initiative. The LB ³ P conducted a prospective, observational cohort study to identify phenotypes of people with cLBP. Here, we report demographic and biomedical characteristics of a large cohort of individuals with cLBP, stratified by sex and age, collected at the in‐person enrollment visit. Methods: The key eligibility criteria were adults with cLBP, English speakers, and identified in the electronic health record of our medical center. Recruitment strategies were through clinical partners who invited their patients to join the study and research registries. Participants completed demographic and biomedical surveys. Descriptive statistics were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60). Results: N = 1007 individuals (60% female) were enrolled, with an average age of 59 ± 17 years. Most participants were non‐Hispanic (90%), White (75%), and 53% attained college or higher education. 54% were married or had a partner, 43% were employed, 38% retired, 41% had an annual household income < $50 000, 20% had been off work for more than 30 days due to low back pain (LBP), 16% had applied for or received disability, and 6% were on worker's compensation. The majority were obese (average BMI of 31.5 kg/m ² ), 61% had back pain for > 5 years, and pain had been ongoing every or nearly every day in 76% of the sample. The participants reported a high prevalence of osteoarthritis (58%), anxiety (40%), depression (40%), vision impairment (35%), and balance problems/falls (31%). Among the chronic overlapping pain conditions, the most common were migraine or headache (29%), irritable bowel syndrome (16%), and temporomandibular joint dysfunction (12%). Previous low back surgery was reported by 25%. The most frequently reported LBP treatments during the previous month were exercise routine done on their own (58%), physical therapy, occupational therapy, or chiropractic care (33%), mindfulness, meditation, or relaxation (22%), and diet or nutrition counseling (21%). Medication intake during the last month was 43% for nonsteroidal anti‐inflammatory drugs, 18% for gabapentin, 13% for opioid, and 10% for antidepressants. Conclusions: Describing comprehensive demographic and biomedical characteristics of individuals with cLBP stratified by sex and age will serve as a reference for clinicians and research planning, particularly with respect to comorbid conditions and utilization of treatment for cLBP. These data will be useful in future efforts to comprehensively phenotype cLBP.