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Background: Mood disorders (anxiety, depression), sleep disorders, and catastrophizing lead to increased post-operative pain perception, increase in postoperative opioid consumption, decreased engagement with physical activity, and increased resource utilization in surgical patients. Psychosocial disorders significantly affect postoperative outcome. Unfortunately, studies focused on perioperative psychological assessment and treatment are scarce. We propose to test whether digital cognitive behavioral intervention (dCBI) can help surgical patients. dCBI such as RxWell™ is a proven treatment for mood disorders in medical patients such as reducing depression in patients with inflammatory bowel disease. We hypothesize that RxWell™ will also be effective in surgical patients. This study aims to test whether RxWell™ can improve preoperative mood disorders and subsequently reduce postoperative pain and opioid requirement in patients scheduled for primary total hip and knee arthroplasty (THA, TKA). We named the trial as the SuRxgWell trial., Methods: This is a randomized, controlled trial that will enroll primary and unilateral THA or TKA patients with anxiety and/or depression symptoms before surgery to receive the SuRxgWell dCBI program and investigate its impact on postoperative outcomes including postoperative pain, anxiety, depression, sleep disorder, and catastrophizing. After signing an informed consent, subjects will be screened using the PROMIS questionnaires, and subjects with a T-score of ≥ 60 on the short Patient-Reported Outcomes Measurement Information System (PROMIS) 4a Anxiety and/or short PROMIS 4a Depression questionnaires will be randomized to either usual care (control group) or the cognitive behavioral intervention, RxWell™, plus usual care (intervention group). The control group will receive information on how to locate tools to address anxiety and depression, whereas the intervention group will have access to SuRxgWell 1 month prior to surgery and up to 3 months after surgery. The allocation will be 3:1 (intervention to control). Investigators will be blinded, but research coordinators approaching patients and research subjects will not. The primary outcome will be day of surgery anxiety or depression symptoms measured with the PROMIS Short Form v1.0 -Anxiety 4a/Depression and Generalized Anxiety Disorder Measure (GAD-7) and Patient Health Questionnaire (PHQ-8). Secondary end points include measuring other health-related quality of life outcomes including sleep disturbance, fatigue, ability to participate in social roles, pain interference, cognitive function, pain catastrophizing, and physical function. Other secondary outcomes include collecting data about preoperative and postoperative pain scores, and pain medication usage, and orthopedic functional recovery at baseline, day of surgery, and 1, 2, and 3 months after the surgery with the Pain Catastrophizing Scale, the Knee injury and Osteoarthritis Outcome Score (KOOS), and Hip injury and Osteoarthritis Outcome Score (HOOS). In addition, subjects will be asked to complete a GAD-7 and PHQ-8 questionnaires bi-weekly (via the RxWell™ app for the interventional group or REDCAP for the control group). Data about postsurgical complications, and resource utilization will also be recorded. We will also receive monthly reports measuring the usage and engagement of RxWell use for each participant randomized to that arm. The primary hypotheses will be assessed with intention-to-treat estimates, and differences in primary outcome will be tested using independent two sample t-tests. This trial is registered to the ClinicalTrials.gov database (NCT05658796) and supported by the DAPM, UPMC Health Plan, and the NIH., Discussion: Our trial will evaluate the feasibility of digital cognitive behavioral intervention as a perioperative tool to improve anxiety and depression before and after major orthopedic surgery in comparison to education. If digital cognitive behavioral intervention proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcomes., (© 2023. The Author(s).)

Background: The establishment of test-retest reliability and reproducibility (TRR) is an important part of validating any research tool, including functional magnetic resonance imaging (fMRI). The primary objective of this study is to investigate the reliability of pseudo-Continuous Arterial Spin Labeling (pCASL) and Blood Oxygen Level Dependent (BOLD) fMRI data acquired across two different scanners in a sample of healthy adults. While single site/single scanner studies have shown acceptable repeatability, TRR of both in a practical multisite study occurring in two facilities spread out across the country with weeks to months between scans is critically needed., Methods: Ten subjects were imaged with similar 3 T MRI scanners at the University of Pittsburgh and Massachusetts General Hospital. Finger-tapping and Resting-state data were acquired for both techniques. Analysis of the resting state data for functional connectivity was performed with the Functional Connectivity Toolbox, while analysis of the finger tapping data was accomplished with FSL. pCASL Blood flow data was generated using AST Toolbox. Activated areas and networks were identified via pre-defined atlases and dual-regression techniques. Analysis for TRR was conducted by comparing pCASL and BOLD images in terms of Intraclass correlation coefficients, Dice Similarity Coefficients, and repeated measures ANOVA., Results: Both BOLD and pCASL scans showed strong activation and correlation between the two locations for the finger tapping tasks. Functional connectivity analyses identified elements of the default mode network in all resting scans at both locations. Multivariate repeated measures ANOVA showed significant variability between subjects, but no significant variability for location. Global CBF was very similar between the two scanning locations, and repeated measures ANOVA showed no significant differences between the two scanning locations., Conclusions: The results of this study show that when similar scanner hardware and software is coupled with identical data analysis protocols, consistent and reproducible functional brain images can be acquired across sites. The variability seen in the activation maps is greater for pCASL versus BOLD images, as expected, however groups maps are remarkably similar despite the low number of subjects. This demonstrates that multi-site fMRI studies of task-based and resting state brain activity is feasible., (© 2022. The Author(s).)

Background: Data linking labor pain and postpartum depression are emerging. Robust, prospective evaluations of this relationship while factoring other important variables are lacking. We assessed perinatal pain and other factors predicting postpartum depression (PPD) symptoms., Methods: Third trimester women, stratified by a priori plan to receive or avoid labor epidural analgesia, were longitudinally followed from the prenatal period through labor and delivery, until 6 weeks and 3 months postpartum. Electronic pain data was collected hourly during labor in real time, capturing pain unpleasantness, intensity, pain management satisfaction, and expectations. Prenatal and postpartum data included anxiety, depression, the Brief Pain Inventory (BPI), pain catastrophizing, resiliency, and perceived social support and stress. The primary outcome was Edinburgh Postnatal Depression Score (EPDS) as a marker of PPD symptoms. The primary pain variable of interest was labor pain emotional valence (unpleasantness burden, area under the curve for entire labor duration). Single and multivariable linear regressions examined perinatal pain variables in relation to EPDS., Results: Of 72 subjects included, 55 planned/received labor epidural analgesia and 17 planned avoidance/avoided it. In the planned epidural group, the emotional valence of labor pain independently predicted six-week EPDS (labor pain unpleasantness burden, R 2  = 0.42, P = 0.002). In addition to labor pain, prenatal and postpartum pain variables from the BPI independently predicted six-week EPDS. Three-month depression scores were linked to labor and acute pain (6 weeks postpartum), but not to chronic (3 months postpartum) pain variables. Intrapartum pain management satisfaction and expectations were largely met or exceeded and did not differ between analgesia groups., Conclusion: For susceptible women, pain at all perinatal time points-prenatal, labor, and postpartum-appear to be independently linked to depression scores at 6 weeks postpartum. The relationships are true, even though satisfaction and expectations regarding labor pain management were met or exceeded. These data support the concept that labor and acute postpartum pain influences both acute and long-term PPD symptoms, although additional data are needed to assess how analgesia preference interacts with these relationships.

Background: Patients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses., Method: Patients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily., Results: OA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05)., Conclusions: These results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes., Trial Registration: ClinicalTrials.Gov Identifier: NCT01383954 . Registered June 22, 2011.

Background: Comorbid psychopathology is an important predictor of poor outcome for many types of treatments for back or neck pain. But it is unknown if this applies to the results of medial branch blocks (MBBs) for chronic low back or neck pain, which involves injecting the medial branch of the dorsal ramus nerves that innervate the facet joints. The objective of this study was to determine whether high levels of psychopathology are predictive of pain relief after MBB injections in the lumbar or cervical spine., Methods: This was a prospective cohort study. Consecutive patients in a pain medicine practice undergoing MBBs of the lumbar or cervical facets with corticosteroids were recruited to participate. Subjects were selected for a MBB based on operationalized selection criteria and the procedure was performed in a standardized manner. Subjects completed the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) just prior to the procedure and at one-month follow up. Scores on the HADS classified the subjects into three groups based on psychiatric symptoms, which formed the primary predictor variable: Low, Moderate, or High levels of psychopathology. The primary outcome measure was the percent improvement in average daily pain rating one-month following an injection. Analysis of variance and chi-square were used to analyze the analgesia and functional rating differences between groups, and to perform a responder analysis., Results: Eighty six (86) subjects completed the study. The Low psychopathology group (n = 37) reported a mean of 23% improvement in pain at one-month while the High psychopathology group (n = 29) reported a mean worsening of -5.8% in pain (p < .001). Forty five percent (45%) of the Low group had at least 30% improvement in pain versus 10% in the High group (p < .001). Using an analysis of covariance, no baseline demographic, social, or medical variables were significant predictors of pain improvement, nor did they mitigate the effect of psychopathology on the outcome., Conclusion: Psychiatric comorbidity is associated with diminished pain relief after a MBB injection performed with steroid at one-month follow-up. These findings illustrate the importance of assessing comorbid psychopathology as part of a spine care evaluation.

Introduction: Despite recent advances in anti-inflammatory therapy, rheumatoid arthritis (RA) patients continue to rate pain as a priority. The etiology of RA pain is likely multifactorial, including both inflammatory and non-inflammatory components. In this study, we examine the association between disease activity, sleep, psychiatric distress and pain sensitivity in RA., Methods: Fifty-nine female RA patients completed questionnaires and underwent pressure pain threshold testing to assess hyperalgesia/allodynia at joint and non-joint sites. Blood samples were taken to measure C-reactive protein (CRP). The association between disease activity, sleep problems, psychiatric distress and pain threshold was assessed using Pearson/Spearman correlations and multivariable linear regression. Disease activity levels, sleep problems and psychiatric distress were compared between RA patients with fibromyalgia and RA patients without fibromyalgia., Results: In unadjusted analyses, CRP was not correlated with pain threshold, but tender joint count was inversely correlated with pain threshold at all sites (P < or = 0.004). Sleep problems were associated with low pain threshold at all sites (P < or = 0.0008). Psychiatric distress was associated with low pain threshold at the wrist and thumbnail (P < or = 0.006). In multivariable linear regression models, CRP was inversely associated with wrist pain threshold (P = 0.003). Sleep problems were inversely associated with pain threshold at all sites (P < or = 0.01), but psychiatric distress was not. Despite differences in pain threshold, CRP levels and sleep problems between RA patients with fibromyalgia and those without fibromyalgia, associations between these variables did not change when patients with fibromyalgia were excluded., Conclusions: Multivariable models are essential in analyses of pain. Among RA patients, inflammation is associated with heightened pain sensitivity at joints. In contrast, poor sleep is associated with diffuse pain sensitivity, as noted in central pain conditions such as fibromyalgia. Future studies examining pain sensitivity at joint and non-joint sites may identify patients with different underlying pain mechanisms and suggest alternative approaches to treating RA pain.

Introduction: Maladaptive physiological responses to stress appear to play a role in chronic inflammatory diseases such as rheumatoid arthritis (RA). However, relatively little stress research in RA patients has involved the study of pain, the most commonly reported and most impairing stressor in RA. In the present study, we compared psychophysical and physiological responses to standardized noxious stimulation in 19 RA patients and 21 healthy controls., Methods: Participants underwent a single psychophysical testing session in which responses to a variety of painful stimuli were recorded, and blood samples were taken at multiple time points to evaluate the reactivity of cortisol, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) to the experience of acute pain., Results: The findings suggest that RA patients display a fairly general hyperalgesia to mechanical and thermal stimuli across several body sites. In addition, while serum cortisol levels did not differ at baseline or following pain testing in patients relative to controls, the RA patients tended to show elevations in serum IL-6 and demonstrated enhanced pain-reactivity of serum levels of TNF-alpha compared with the healthy controls (P < 0.05)., Conclusions: These findings highlight the importance of pain as a stressor in RA patients and add to a small body of literature documenting amplified responses to pain in RA. Future studies of the pathophysiology of RA would benefit from the consideration of acute pain levels when comparing RA patients with other groups, and future trials of analgesic interventions in RA patients may benefit from evaluating the effects of such interventions on inflammatory activity.