A Systematic Review and Meta-Analysis of Social Cognition Among People Living with HIV: Implications for Non-Social Cognition and Social Everyday Functioning.

Social cognition-the complex mental ability to perceive social stimuli and negotiate the social environment-has emerged as an important cognitive ability needed for social functioning, everyday functioning, and quality of life. Deficits in social cognition have been well documented in those with severe mental illness including schizophrenia and depression, those along the autism spectrum, and those with other brain disorders where such deficits profoundly impact everyday life. Moreover, subtle deficits in social cognition have been observed in other clinical populations, especially those that may have compromised non-social cognition (i.e., fluid intelligence such as memory). Among people living with HIV (PLHIV), 44% experience cognitive impairment; likewise, social cognitive deficits in theory of mind, prosody, empathy, and emotional face recognition/perception are gradually being recognized. This systematic review and meta-analysis aim to summarize the current knowledge of social cognitive ability among PLHIV, identified by 14 studies focused on social cognition among PLHIV, and provides an objective consensus of the findings. In general, the literature suggests that PLHIV may be at-risk of developing subtle social cognitive deficits that may impact their everyday social functioning and quality of life. The causes of such social cognitive deficits remain unclear, but perhaps develop due to (1) HIV-related sequelae that are damaging the same neurological systems in which social cognition and non-social cognition are processed; (2) stress related to coping with HIV disease itself that overwhelms one's social cognitive resources; or (3) may have been present pre-morbidly, possibly contributing to an HIV infection. From this, a theoretical framework is proposed highlighting the relationships between social cognition, non-social cognition, and social everyday functioning.

Priorities for HIV and chronic pain research: results from a survey of individuals with lived experience.

The Global Task Force on Chronic Pain in HIV published seven research priorities in the field of HIV-associated chronic pain in 2019: (1) causes; (2) management; (3) treatment individualization and integration with addiction treatment; (4) mental and social health factors; (5) prevalence; (6) treatment cost effectiveness; and (7) prevention. The current study used a web-based survey to determine whether the research topics were aligned with the priorities of adults with lived experiences of HIV and chronic pain. We also collected information about respondents' own pain and treatment experiences. We received 311 survey responses from mostly US-based respondents. Most respondents reported longstanding, moderate to severe, multisite pain, commonly accompanied by symptoms of anxiety and/or depression. The median number of pain treatments tried was 10 (IQR = 8, 13), with medications and exercise being the most common modalities, and opioids being viewed as the most helpful. Over 80% of respondents considered all research topics either "extremely important" or "very important". Research topic #2, which focused on optimizing management of pain in people with HIV, was accorded the greatest importance by respondents. These findings suggest good alignment between the priorities of researchers and US-based people with lived experience of HIV-associated chronic pain.

Improving Sleep in People with HIV and Chronic Pain: A Pilot Study of Brief Behavioral Treatment for Insomnia.

OBJECTIVES: Insomnia and chronic pain are common symptoms in people with HIV. Poor sleep has been associated with chronic pain. While cognitive behavioral therapy for insomnia improves insomnia in clinical populations, there are barriers to people with HIV accessing treatment including the lack of trained providers and lengthy sessions. Only one study has examined the efficacy of brief behavioral treatment for insomnia (BBTI) in people with HIV. This study examined BBTI effects on sleep and pain in people with HIV. METHODS: Ten adults with HIV and chronic pain completed a 4-week, telephone-delivered BBTI treatment. A control group (n = 10) completed a brief mindfulness training (BMT). The Insomnia Severity Index and Brief Pain Inventory were used to assess insomnia severity and pain outcomes, respectively. RESULTS: There was a significant interaction between intervention and time on insomnia severity, F (2,14) = 5.7, p = .02, partial η2 = 0.45). The BBTI group demonstrated significant improvements in insomnia severity from pre- to post-intervention (p < .001) and from pre-intervention to one-month post-intervention (p = .001) compared to the BMT group. There was a significant interaction between intervention and time on pain interference, F (1,18) = 4.9, p = .02, partial η2 = 0.27). The BBTI group demonstrated a significant decrease in pain interference from pre- to post-intervention (p < .001) compared to the BMT group. CONCLUSIONS: This pilot study demonstrated that BBTI improved insomnia in people with HIV for up to one-month post-treatment. Novel preliminary evidence suggests that BBTI may also improve pain outcomes in people with HIV.

Mitochondrial reactivity following acute exposure to experimental pain testing in people with HIV and chronic pain.

Background: Physical stressors can cause a physiological response that can contribute to an increase in mitochondrial dysfunction and Mitochondrial DNA damage (mtDNA damage). People living with HIV (PWH) are more likely to suffer from chronic pain and may be more susceptible to mitochondrial dysfunction following exposure to a stressor. We used Quantitative Sensory Testing (QST) as an acute painful stressor in order to investigate whether PWH with/without chronic pain show differential mitochondrial physiological responses. Methods: The current study included PWH with (n = 26), and without (n = 29), chronic pain. Participants completed a single session that lasted approximately 180 min, including QST. Blood was taken prior to and following the QST battery for assays measuring mtDNA damage, mtDNA copy number, and mtDNA damage-associated molecular pattern (DAMP) levels (i.e., ND1 and ND6). Results: We examined differences between those with and without pain on various indicators of mitochondrial reactivity following exposure to QST. However, only ND6 and mtDNA damage were shown to be statistically significant between pain groups. Conclusion: PWH with chronic pain showed greater mitochondrial reactivity to laboratory stressors. Consequently, PWH and chronic pain may be more susceptible to conditions in which mitochondrial damage/dysfunction play a central role, such as cognitive decline.

The pace of biological aging helps explain the association between insomnia and chronic low back pain.

Chronic low back pain (cLBP) is associated with insomnia and advanced age. Emerging evidence suggests that the severity of both sleep disorders (like insomnia) and chronic pain are associated with a faster pace of biological aging. We aimed to determine whether the pace of biological age mediates the relationship between insomnia and the impact of cLBP in a sample of community-dwelling adults ages 19 to 85 years. Participants (49 with no pain, 32 with low-impact pain, and 37 with high-impact pain) completed sociodemographic, pain, insomnia, and short physical performance battery assessments. We calculated the pace of biological aging using DunedinPACE from blood leukocyte DNA. On average, individuals with high-impact cLBP had significantly faster biological aging than those with low-impact and no chronic pain (p < .001). Bivariate associations of DunedinPACE scores with insomnia severity and functional performance were significant at p < .01 (rs = 0.324 and -0.502, respectively). After adjusting for race and sex, the association of insomnia severity and the impact of cLBP was partially mediated by the pace of biological aging (ß = 0.070, p < .001). Also, the association of insomnia severity with functional performance was partially mediated by the pace of biological aging (ß = -0.105, p < .001). Thus, insomnia remains strongly predictive of cLBP outcomes, and the pace of biological aging helps explain this association. Future prospective studies with repeated assessments are needed to uncover the directionality of these complex relationships and ultimately develop interventions to manage cLBP.

Pain-Related Stigma and Its Associations With Clinical and Experimental Pain Severity in Youth With Chronic Musculoskeletal Pain Conditions.

OBJECTIVE: Many children with chronic musculoskeletal pain conditions experience stigma which can have negative downstream consequences. This study compares ratings of clinical pain (current pain intensity and pain interference), experimental pain (temporal summation, cold water tolerance, and cold pain intensity), and pain-related stigma among three groups of youth with rheumatic conditions. The relations among ratings of pain-related stigma and pain variables were explored. METHODS: Eighty-eight youth aged 8-17 years with a diagnosis of juvenile idiopathic arthritis (JIA = 32), juvenile fibromyalgia (JFM = 31), or non-specific chronic pain (NSCP = 25) completed measures of clinical pain ratings (average 7-day pain intensity, day of assessment pain (DoA), and pain interference), experimental pain (cold pain tolerance, cold pain intensity, and temporal summation of mechanical pain), and pain-related stigma. Data analysis compared pain-related stigma and pain ratings across the three groups and examined the relations among pain-related stigma and pain ratings. RESULTS: Youth with JFM reported higher ratings of clinical pain and pain-related stigma than their counterparts with NSCP or JIA. However, there were no differences in experimental pain. Pain-related stigma was associated with greater ratings of pain interference, particularly for those with JIA and NSCP. Pain-related stigma was also associated with greater average daily pain intensity but not DoA. CONCLUSION: Youth with medically unexplained pain report greater stigma and worse pain than their peers; thus, robust assessment of pain in this population is necessary. Future work should longitudinally explore the impact of pain-related stigma on pain outcomes and treatment responses.

Adversity type and timing predict temporal summation of pain in African-American adults.

African Americans are disproportionately exposed to adversity across the lifespan, which includes both stressful and traumatic events. Adversity, in turn, is associated with alterations in pain responsiveness. Racial differences in pain responsiveness among healthy adults are well established. However, the extent to which adversity type and timing are associated with alterations in pain responsiveness among healthy African-American adults is not well understood. The present study included 160 healthy African-American adults (98 women), ages 18 to 45. Outcome measures included pain tolerance and temporal summation of pain to evoked thermal pain. Composite scores were created for early-life adversity (childhood trauma, family adversity) and recent adversity (perceived stress, chronic stress burden). A measure of lifetime racial discrimination was also included. Higher levels of recent adversity were associated with higher temporal summation of pain, controlling for gender, age, and education. Neither early-life adversity nor lifetime racial discrimination were associated with temporal summation of pain. The present findings suggest that heightened temporal summation of pain among healthy African-American adults is associated with exposure to recent adversity events. Improved understanding of how recent adversity contributes to heightened temporal summation of pain in African Americans could help to mitigate racial disparities in pain experiences by identifying at-risk individuals who could benefit from early interventions.

Self-reported pain and fatigue are associated with physical and cognitive function in middle to older-aged adults.

Persistent fatigue is often reported in those with chronic musculoskeletal pain. Separately, both chronic pain and chronic fatigue contribute to physical and cognitive decline in older adults. Concurrent pain and fatigue symptoms may increase disability and diminish quality of life, though little data exist to show this. The purpose of this study was to examine associations between self-reported pain and fatigue, both independently and combined, with cognitive and physical function in middle-older-aged adults with chronic knee pain. Using a cross-sectional study design participants (n = 206, age 58.0 ± 8.3) completed questionnaires on pain and fatigue, a physical performance battery to assess physical function, and the Montreal Cognitive Assessment. Hierarchical regressions and moderation analyses were used to assess the relationship between the variables of interest. Pain and fatigue both predicted physical function (ß = -0.305, p < 0.001; ß = -0.219, p = 0.003, respectively), however only pain significantly predicted cognitive function (ß = -0.295, p <0.001). A centered pain*fatigue interaction was a significant predictor of both cognitive function (ß = -0.137, p = 0.049) and physical function (ß = -0.146, p = 0.048). These findings indicate that self-reported fatigue may contribute primarily to decline in physical function among individuals with chronic pain, and less so to decline in cognitive function. Future studies should examine the impact of both cognitive and physical function decline together on overall disability and health.

Associations between pain catastrophizing and resting-state functional brain connectivity: Ethnic/race group differences in persons with chronic knee pain.

Chronic pain is a significant public health problem, and the prevalence and societal impact continues to worsen annually. Multiple cognitive and emotional factors are known to modulate pain, including pain catastrophizing, which contributes to pain facilitation and is associated with altered resting-state functional connectivity in pain-related cortical and subcortical circuitry. Pain and catastrophizing levels are reported to be higher in non-Hispanic black (NHB) compared with non-Hispanic White (NHW) individuals. The current study, a substudy of a larger ongoing observational cohort investigation, investigated the pathways by which ethnicity/race influences the relationship between pain catastrophizing, clinical pain, and resting-state functional connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), insula, and primary somatosensory cortex (S1). Participants included 136 (66 NHBs and 70 NHWs) community-dwelling adults with knee osteoarthritis. Participants completed the Coping Strategies Questionnaire-Revised Pain Catastrophizing subscale and Western Ontario and McMaster Universities Osteoarthritis Index. Magnetic resonance imaging data were obtained, and resting-state functional connectivity was analyzed. Relative to NHW, the NHB participants were younger, reported lower income, were less likely to be married, and self-reported greater clinical pain and pain catastrophizing (ps < 0.05). Ethnicity/race moderated the mediation effects of catastrophizing on the relationship between clinical pain and resting-state functional connectivity between the ACC, dlPFC, insula, and S1. These results indicate the NHB and NHW groups demonstrated different relationships between pain, catastrophizing, and functional connectivity. These results provide evidence for a potentially important role of ethnicity/race in the interrelationships among pain, catastrophizing, and resting-state functional connectivity.

Somatic Symptoms in Adolescents With an Ill Parent.

OBJECTIVE: Parent chronic illness may increase somatic symptomology risk in children. The current study examines this association in relation to a variety of chronic illnesses and also considers possible related parental and adolescent background factors. METHODS: Secondary analyses used longitudinal data from the University of North Carolina National Longitudinal Study of Adolescent to Adult Health. Interviews were used to assess demographics, adolescent somatic symptoms, living situation, and parental illness and general physical health. Somatic symptoms in adolescents with no ill parents (n = 2302 adolescents; Mage = 15.3) were compared with adolescents with ill mothers (n = 2336; Mage = 15.3), ill fathers (n = 1304; Mage = 15.3), or two ill parents (n = 3768; Mage = 15.3) using Poisson regression models. We also examined the role of living status, adolescent sex, and parent general physical health on somatic symptom outcomes. RESULTS: Elevated somatic symptoms were observed in adolescents with ill mothers (mean ratio [MR] = 1.15, p = .015) and with both parents ill (MR = 1.10, p < .001). Among adolescents with ill parents, females had more symptoms than males (ill mother: MR = 1.12, p < .001; ill father: MR = 1.23, p < .001; and both parents ill: MR = 1.23, p < .001). Poorer maternal physical health also increased somatic symptom risk (MR = 1.12, p = .02). Longitudinally, adolescents with ill mothers (MR = 1.14, p < .001), ill fathers (MR = 1.13, p < .001), or both parents ill (MR = 1.16, p < .001) had increased somatic symptom risk. Wave I somatic symptoms also increased future risk: ill mother (MR = 1.19, p < .001), ill father (MR = 1.22, p < .001), or both parents ill (MR = 1.20, p < .001). CONCLUSIONS: The results highlight that having an ill parent is a risk factor for adolescent somatic symptoms. In addition, other factors such as adolescent sex play an additional role in adolescent somatic symptoms.

Insomnia severity and depressive symptoms in people living with HIV and chronic pain: associations with opioid use.

Chronic pain commonly occurs in people living with HIV (PLWH). Many PLWH in the United States obtain opioids for chronic pain management. Whether insomnia severity and depressive symptoms are exacerbated by chronic pain and opioid use in PLWH remains to be determined. This study examined insomnia severity and depressive symptoms in 85 PLWH with chronic pain and 35 PLWH without chronic pain. Among PLWH with chronic pain, reported opioid use was examined in relation to insomnia severity and depressive symptoms. PLWH with chronic pain reported significantly greater insomnia severity (p = .033) and depressive symptoms (p = .025) than PLWH without chronic pain. Among PLWH with chronic pain who reported opioid use (n = 36), insomnia severity was greater compared to those who denied opioid use (n = 49), even after controlling for pain severity and number of comorbidities (p = .026). Greater pain severity was significantly associated with greater insomnia severity (p < .001) and depressive symptoms (p = .048) among PLWH with chronic pain who reported opioid use. These associations were not significant among those PLWH with chronic pain who denied opioid use. Findings suggest that PLWH with chronic pain are likely to experience poor sleep and depressed mood. Furthermore, poor sleep was associated with opioid use among PLWH with chronic pain.

Preserving independence among under-resourced older adults in the Southeastern United States: existing barriers and potential strategies for research.

Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as "the Deep South", is an economically and culturally unique region ravaged by pervasive health disparities - thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region.

Exemptions to state laws regulating opioid prescribing for patients with cancer-related pain: A summary.

BACKGROUND: Cancer-related pain is highly prevalent and is commonly treated with prescription opioids. The Centers for Disease Control and Prevention (CDC) now encourages conservative opioid prescribing in recognition of potential opioid-related risks. However, CDC guidelines have been misapplied to patients with cancer. Recent laws at the state level reflect the CDC's guidance by limiting opioid prescribing. It is unclear whether states exempt cancer-related pain, which may affect cancer pain management. Thus, the objective of this study was to summarize current state-level opioid prescribing laws and exemptions for patients with cancer. METHODS: Two study authors reviewed publicly available state records to identify the most recent opioid prescribing laws and cancer-related exemptions. Documents were required to have the force of law and be enacted at the time of the search (November 2020). RESULTS: Results indicated that 36 states had enacted formal legislation limiting the duration and/or dosage of opioid prescriptions, and this was largely focused on acute pain and/or initial prescriptions. Of these states, 32 (89%) explicitly exempted patients with cancer-related pain from opioid prescribing laws. Exemptions were broadly applied, with few states providing specific guidance for cancer-related pain prescribing. CONCLUSIONS: The results of this study indicate that most states recognize the importance of prescription opioids in cancer-related pain management. However, drafting nuanced and clinically relevant opioid legislation is challenging for a heterogenous population. Additionally, current attempts to regulate opioid prescribing by state law may unintentionally undermine patient-centered approaches to pain management. Additional resources are needed to facilitate clarity at the intersection of opioid-related legislation and clinical management for cancer-related pain. LAY SUMMARY: In this review of state-level legislation, current limitations on opioid prescribing are summarized and detailed information is provided on exemptions for patients with cancer. The majority of states have enacted specific dosage and/or duration limitations on opioid prescribing while including broad exemptions for cancer-related pain. Cancer-related pain exemptions are important to include, as is consistent with national and professional guidelines (eg, the Centers for Disease Control and Prevention). However, these exemptions may also unintentionally undermine patient-centered approaches to pain management. Additional resources, including specific guidance for patients with cancer, are needed to facilitate clarity at the intersection of opioid-related legislation and clinical pain management. ​.

Resilience, pain, and the brain: Relationships differ by sociodemographics.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45-85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.

Sleep and neighborhood socioeconomic status: a micro longitudinal study of chronic low-back pain and pain-free individuals.

Individuals with chronic low back pain (cLBP) frequently report sleep disturbances. Living in a neighborhood characterized by low-socioeconomic status (SES) is associated with a variety of negative health outcomes, including poor sleep. Whether low-neighborhood SES exacerbates sleep disturbances of people with cLBP, relative to pain-free individuals, has not previously been observed. This study compared associations between neighborhood-level SES, pain-status (cLBP vs. pain-free), and daily sleep metrics in 117 adults (cLBP = 82, pain-free = 35). Neighborhood-level SES was gathered from Neighborhood Atlas, which provides a composite measurement of overall neighborhood deprivation (e.g. area deprivation index). Individuals completed home sleep monitoring for 7-consecutive days/nights. Neighborhood SES and pain-status were tested as predictors of actigraphic sleep variables (e.g., sleep efficiency). Analyses revealed neighborhood-level SES and neighborhood-level SES*pain-status interaction significantly impacted objective sleep quality. These findings provide initial support for the negative impact of low neighborhood-level SES and chronic pain on sleep quality.

Knee pain trajectories over 18 months in non-Hispanic Black and non-Hispanic White adults with or at risk for knee osteoarthritis.

BACKGROUND: Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics. METHODS: The sample included a prospective cohort of 188 participants (mean age 58 years; 63% female; 52% non-Hispanic Black) with or at risk for knee OA from an ongoing multisite investigation of ethnic/race group differences. Knee pain intensity was self-reported at baseline and quarterly over an18-month period. Baseline pain assessment also included frequency, duration, and total number of pain sites. Group-based trajectory modeling was used to identify distinct pain trajectories. Multinomial logistic regression was used to examine associations between sociodemographic characteristics, risk factors, and pain trajectory groups. RESULTS: Pain trajectories were relatively stable among a sample of adults with knee pain. Four distinct pain trajectories emerged in the overall sample, with the largest proportion of participants (35.1%) classified in the moderate-high pain group. There were significant relationships between age, education, income, ethnicity/race and trajectory group; with younger, less educated, lower income, and non-Hispanic Black participants had a greater representation in the highest pain trajectory group. CONCLUSIONS: Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. Certain sociodemographic variables (e.g. ethnicity/race, education, income, age) may contribute to an increased risk of experiencing greater pain.

Temporal summation of mechanical pain prospectively predicts movement-evoked pain severity in adults with chronic low back pain.

BACKGROUND: Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire. METHODS: One hundred thirty-four individuals with chronic low back pain were enrolled in this two-session study. During the first study session, temporal summation of mechanical pain and conditioned pain modulation were assessed at the lumbar spine to determine endogenous pain facilitation and inhibition, respectively. One week later, participants returned for a second study session whereby they reported their pain severity and pain interference using the Brief Pain Inventory-Short Form. Movement-evoked pain and physical function capacity were assessed upon completion of the balance, walking, and transition from sit to stand tests of the Short Physical Performance Battery. RESULTS: Temporal summation of mechanical pain, but not conditioned pain modulation, significantly and prospectively predicted greater movement-evoked pain and poorer physical function on the Short Physical Performance Battery. Neither temporal summation nor conditioned pain modulation were significantly related to self-reported pain severity or pain interference on the Brief Pain Inventory-Short Form. CONCLUSIONS: Findings suggest that a pro-nociceptive pain modulatory balance characterized by enhanced pain facilitation may be an important driver of movement-evoked pain severity and poor physical function in individuals with chronic low back pain.

Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain.

Chronic low back pain (cLBP) that cannot be attributable to a specific pathoanatomical change is associated with high personal and societal costs. Still, the underlying mechanism that causes and sustains such a phenotype is largely unknown. Emerging evidence suggests that epigenetic changes play a role in chronic pain conditions. Using reduced representation bisulfite sequencing (RRBS), we evaluated DNA methylation profiles of adults with non-specific cLBP (n = 50) and pain-free controls (n = 48). We identified 28,325 hypermethylated and 36,936 hypomethylated CpG sites (p < 0.05). After correcting for multiple testing, we identified 159 DMRs (q < 0.01and methylation difference > 10%), the majority of which were located in CpG island (50%) and promoter regions (48%) on the associated genes. The genes associated with the differentially methylated regions were highly enriched in biological processes that have previously been implicated in immune signaling, endochondral ossification, and G-protein coupled transmissions. Our findings support inflammatory alterations and the role of bone maturation in cLBP. This study suggests that epigenetic regulation has an important role in the pathophysiology of non-specific cLBP and a basis for future studies in biomarker development and targeted interventions.

Risk models for predicting the health-related quality of life of caregivers of youth with gastrointestinal concerns.

PURPOSE: To determine the usefulness of cumulative and additive risk models in predicting the healthy-related quality of life (HRQOL) of caregivers of youth with chronic gastrointestinal conditions. METHODS: 203 caregivers (82.8% mothers; 77.3% white) of youth (M = 11.27 years; 44.3% female; 78.8% White) completed self-report questionnaires focused on potential environmental, child health, and family risk factors that could impact caregiver HRQOL. Cumulative risk models, evaluating overall combined risk level, as well as an additive risk model, exploring individual risk variables, were evaluated. RESULTS: Higher levels of cumulative risk were associated with poorer caregiver HRQOL after controlling for child and caregiver sex. A linear cumulative risk model was a better fit than a quadratic cumulative risk model for predicting caregiver HRQOL, while an additive model identified child HRQOL, child pain interference and family functioning as the most individually impactful risk variables. CONCLUSION: This study illustrates the usefulness of both additive and cumulative risk approaches in identifying caregivers at risk for poor HRQOL. Provision of appropriate referrals and interventions based on the caregiver's risk factors can help protect caregiver quality of life and, in turn, benefit the care children with chronic conditions receive at home.

Perceived Injustice Helps Explain the Association Between Chronic Pain Stigma and Movement-Evoked Pain in Adults with Nonspecific Chronic Low Back Pain.

OBJECTIVE: For most patients with chronic low back pain (cLBP), the cause is "nonspecific," meaning there is no clear association between pain and identifiable pathology of the spine or associated tissues. Laypersons and providers alike are less inclined to help, feel less sympathy, dislike patients more, suspect deception, and attribute lower pain severity to patients whose pain does not have an objective basis in tissue pathology. Because of these stigmatizing responses from others, patients with cLBP may feel that their pain is particularly unjust and unfair. These pain-related injustice perceptions may subsequently contribute to greater cLBP severity. The purpose of this study was to examine whether perceived injustice helps explain the relationship between chronic pain stigma and movement-evoked pain severity among individuals with cLBP. METHODS: Participants included 105 patients with cLBP who completed questionnaires assessing chronic pain stigma and pain-related injustice perception, as well as a short physical performance battery for the assessment of movement-evoked pain and physical function. RESULTS: Findings revealed that perceived injustice significantly mediated the association between chronic pain stigma and cLBP severity (indirect effect = 6.64, 95% confidence interval [CI] = 2.041 to 14.913) and physical function (indirect effect = -0.401, 95% CI = -1.029 to -0.052). Greater chronic pain stigma was associated with greater perceived injustice (P = 0.001), which in turn was associated with greater movement-evoked pain severity (P = 0.003). CONCLUSIONS: These results suggest that perceived injustice may be a means through which chronic pain stigma impacts nonspecific cLBP severity and physical function.