Assessing the potential anti-neuroinflammatory effect of minocycline in chronic low back pain: Protocol for a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain. METHODS AND ANALYSIS: This study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-75, with a confirmed diagnosis of chronic (≥ six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) using [11C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuroinflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models will be used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03106740).

Loneliness and Pain Catastrophizing Among Individuals with Chronic Pain: The Mediating Role of Depression.

Purpose: Loneliness increased during the COVID-19 pandemic and social distancing guidelines, potentially exacerbating negative cognitions about pain. The present study investigated the longitudinal relationship between loneliness, assessed during the early weeks of the pandemic, and pain catastrophizing, assessed after living in the pandemic for approximately 1 year, among chronic pain patients. We also examined whether severity of depressive symptoms mediated this association. Methods: This prospective longitudinal study recruited individuals with chronic pain (N=93) from Massachusetts using an online convenience sampling method via the platform Rally. Participants completed an initial survey early after the onset of social distancing (4/28/20-6/17/20; Time 1) and a follow-up survey 1 year later (5/21/21-6/7/21; Time 2). Participants completed validated assessments of loneliness (T1), pain catastrophizing (T2), and depression (T2). Spearman correlations and Mann-Whitney U-tests were used to explore associations among psychosocial, pain, and participant characteristics. A mediation analysis was conducted to test whether the association between loneliness and pain catastrophizing was mediated by depression. Results: Participants had a mean age of 40.6 years and were majority female (80%) and White (82%). Greater loneliness was associated with subsequent higher pain catastrophizing (b=1.23, 95% CI [0.03, 2.44]). Mediation analysis showed a significant indirect effect (b=0.57, 95% CI [0.10, 1.18) of loneliness (T1) on catastrophizing (T2) through depression (T2) while accounting for several important covariates. The direct effect of loneliness on catastrophizing was no longer significant when depression was included in the model (b=0.66, 95% CI [-0.54, 1.87]). Conclusion: Findings suggest that greater loneliness during the pandemic was associated with higher pain catastrophizing 1 year later, and severity of depression after living in the pandemic mediated this association. As loneliness, depression, and catastrophizing can all be modified with behavioral interventions, understanding the temporal associations among these variables is important for the employment of future empirically supported treatments.

Introversion, Extraversion, and Worsening of Chronic Pain Impact during Social Isolation: A Mediation Analysis.

COVID-19 social distancing mandates increased social isolation, resulting in changes in pain severity and interference among individuals with chronic pain. Differences in personality (e.g., introversion/extraversion) may modulate responses to social isolation. We examined the influence of introversion on reported social distancing-related increases in pain interference and assessed for mediators of this relationship. Individuals with chronic pain (n = 150) completed validated questionnaires 4-8 weeks after implementation of social distancing mandates. Introversion/extraversion was measured using a subscale of the Myers-Briggs Type Indicator and changes in pain and psychosocial variables were calculated by comparing participants' recalled and current scores. Association between introversion/extraversion and other variables were assessed using linear regression. A parallel mediation was used to examine mediators of the association between introversion and change in pain interference. Higher introversion was associated with a decrease in pain interference after social distancing (Rho = - .194, p = .017). Parallel mediation analysis revealed that the relationship between introversion/extraversion and change in pain interference was mediated by changes in sleep disturbance and depression, such that higher introversion was associated with less isolation-induced sleep disruption and depression, and thereby less worsening of pain interference. These findings suggest that personality factors such as introversion/extraversion should be considered when personalizing treatment of chronic pain.

Profiles of Risk and Resilience in Chronic Pain: Loneliness, Social Support, Mindfulness, and Optimism Coming out of the First Pandemic Year.

OBJECTIVE: Individuals experience chronic pain differently, not only because of different clinical diagnoses, but also because of differing degrees of influence from biopsychosocial pain modulators. We aimed to cluster patients with chronic pain into distinct subgroups based on psychosocial characteristics and pain intensity, and we subsequently examined group differences in pain-related interference approximately 1 year later. METHODS: In this observational, longitudinal study, patients with chronic pain (n = 94) completed validated assessments of psychosocial characteristics and pain intensity at the beginning of COVID-19-related social distancing (April to June 2020). One year later (May to June 2021), patients completed a follow-up survey with assessments of pain interference, loneliness, social support, mindfulness, and optimism. RESULTS: A cluster analysis, using psychosocial factors and pain intensity, empirically produced three patient groups: 1) psychosocial predominant (PSP), characterized by high psychosocial distress and average pain intensity; 2) pain intensity predominant (PIP), characterized by average psychosocial distress and high pain intensity; and 3) less elevated symptoms (LES), characterized by low psychosocial distress and low pain intensity. At the 1-year follow-up, patients in the PSP and PIP clusters suffered greater pain interference than patients in the LES cluster, while patients in the PSP cluster also reported greater loneliness and lower mindfulness and optimism. CONCLUSIONS: An empirical psychosocial-based clustering of patients identified three distinct groups that differed in pain interference. Patients with high psychosocial modulation of pain at the onset of social distancing (the PSP cluster) suffered not only greater pain interference but also greater loneliness and lower levels of mindfulness and optimism, which suggests some potential behavioral targets for this group in the future.

Assessing the impact of the COVID-19 pandemic on pragmatic clinical trial participants.

Characterizing the impacts of disruption attributable to the COVID-19 pandemic on clinical research is important, especially in pain research where psychological, social, and economic stressors attributable to the COVID-19 pandemic may greatly impact treatment effects. The National Institutes of Health - Department of Defense - Department of Veterans Affairs Pain Management Collaboratory (PMC) is a collective effort supporting 11 pragmatic clinical trials studying nonpharmacological approaches and innovative integrated care models for pain management in veteran and military health systems. The PMC rapidly developed a brief pandemic impacts measure for use across its pragmatic trials studying pain while remaining broadly applicable to other areas of clinical research. Through open discussion and consensus building by the PMC's Phenotypes and Outcomes Work Group, the PMC Coronavirus Pandemic (COVID-19) Measure was iteratively developed. The measure assesses the following domains (one item/domain): access to healthcare, social support, finances, ability to meet basic needs, and mental or emotional health. Two additional items assess infection status (personal and household) and hospitalization. The measure uses structured responses with a three-point scale for COVID-19 infection status and four-point ordinal rank response for all other domains. We recommend individualized adaptation as appropriate by clinical research teams using this measure to survey the effects of the COVID-19 pandemic on study participants. This can also help maintain utility of the measure beyond the COVID-19 pandemic to characterize impacts during future public health emergencies that may require mitigation strategies such as periods of quarantine and isolation.

Cross-sectional study of psychosocial and pain-related variables among patients with chronic pain during a time of social distancing imposed by the coronavirus disease 2019 pandemic.

ABSTRACT: The COVID-19 pandemic has had a tremendous impact, including on individuals with chronic pain. The social distancing policies necessary to slow the spread of SARS-CoV-2 have involved increased levels of social isolation. This cross-sectional survey study examined pain severity and interference among individuals with chronic pain during an early phase of social distancing mandates and identified characteristics of individuals who were most impacted. Approximately 4 to 8 weeks after social distancing mandates commenced in the state of Massachusetts, 150 patients with fibromyalgia, chronic spine, and postsurgical pain completed demographic, pain, social distancing, and validated psychosocial questionnaires. Patients self-reported an overall significant increase in pain severity and pain interference, compared with before social distancing, although both pain severity and interference were quite variable among individuals under conditions of social distancing. Several demographic, socioeconomic, and psychosocial factors were associated with greater pain severity and interference during social distancing. Multivariable linear regression demonstrated that female sex, nonwhite race, lower education, disability, fibromyalgia, and higher pain catastrophizing were independently associated with greater pain severity, while female sex and pain catastrophizing were independently associated greater pain interference. The findings suggest that individual differences among patients with chronic pain should be considered in the planning, development, and prioritization of interventions to improve pain care and to prevent worsening of symptoms during the continuing COVID-19 pandemic.