Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer\u27s disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. METHODS: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n = 72) and non-Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. RESULTS: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p \u3c .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). IMPLICATIONS: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes

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

Brain-predicted age difference mediates the association between PROMIS sleep impairment, and self-reported pain measure in persons with knee pain

Knee pain, the most common cause of musculoskeletal pain (MSK), constitutes a severe public health burden. Its neurobiological causes, however, remain poorly understood. Among many possible causes, it has been proposed that sleep problems could lead to an increase in chronic pain symptomatology, which may be driven by central nervous system changes. In fact, we previously found that brain cortical thickness mediated the relationship between sleep qualities and pain severity in older adults with MSK. We also demonstrated a significant difference in a machine-learning-derived brain-aging biomarker between participants with low-and high-impact knee pain. Considering this, we examined whether brain aging was associated with self-reported sleep and pain measures, and whether brain aging mediated the relationship between sleep problems and knee pain. Exploratory Spearman and Pearson partial correlations, controlling for age, sex, race and study site, showed a significant association of brain aging with sleep related impairment and self-reported pain measures. Moreover, mediation analysis showed that brain aging significantly mediated the effect of sleep related impairment on clinical pain and physical symptoms. Our findings extend our prior work demonstrating advanced brain aging among individuals with chronic pain and the mediating role of brain-aging on the association between sleep and pain severity. Future longitudinal studies are needed to further understand whether the brain can be a therapeutic target to reverse the possible effect of sleep problems on chronic pain

Implications of preoperative depression for lumbar spine surgery outcomes: A systematic review and meta-analysis

IMPORTANCE: Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive. OBJECTIVE: To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery. DATA SOURCES: A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.gov was performed from database inception to September 14, 2023. STUDY SELECTION: Included studies involved adults undergoing lumbar spine surgery and compared PROMs in patients with vs those without depression. Studies evaluating the correlation between preoperative depression and disease severity were also included. DATA EXTRACTION AND SYNTHESIS: All data were independently extracted by 2 authors and independently verified by a third author. Study quality was assessed using Newcastle-Ottawa Scale. Random-effects meta-analysis was used to synthesize data, and I2 was used to assess heterogeneity. Metaregression was performed to identify factors explaining the heterogeneity. MAIN OUTCOMES AND MEASURES: The primary outcome was the standardized mean difference (SMD) of change from preoperative baseline to postoperative follow-up in PROMs of disability, pain, and physical function for patients with vs without depression. Secondary outcomes were preoperative and postoperative differences in absolute disease severity for these 2 patient populations. RESULTS: Of the 8459 articles identified, 44 were included in the analysis. These studies involved 21 452 patients with a mean (SD) age of 57 (8) years and included 11 747 females (55%). Among these studies, the median (range) follow-up duration was 12 (6-120) months. The pooled estimates of disability, pain, and physical function showed that patients with depression experienced a greater magnitude of improvement compared with patients without depression, but this difference was not significant (SMD, 0.04 [95% CI, -0.02 to 0.10]; I2 = 75%; P = .21). Nonetheless, patients with depression presented with worse preoperative disease severity in disability, pain, and physical function (SMD, -0.52 [95% CI, -0.62 to -0.41]; I2 = 89%; P \u3c .001), which remained worse postoperatively (SMD, -0.52 [95% CI, -0.75 to -0.28]; I2 = 98%; P \u3c .001). There was no significant correlation between depression severity and the primary outcome. A multivariable metaregression analysis suggested that age, sex (male to female ratio), percentage of comorbidities, and follow-up attrition were significant sources of variance. CONCLUSIONS AND RELEVANCE: Results of this systematic review and meta-analysis suggested that, although patients with depression had worse disease severity both before and after surgery compared with patients without depression, they had significant potential for recovery in disability, pain, and physical function. Further investigations are needed to examine the association between spine-related disability and depression as well as the role of perioperative mental health treatments

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.</p

Brief Report: IL-1β Levels Are Associated With Chronic Multisite Pain in People Living With HIV

BACKGROUND: The pathophysiology of chronic pain experienced by people living with HIV (PLWH) in the current antiretroviral treatment era is poorly understood. We sought to investigate the relationship between inflammation and chronic pain in PLWH. We hypothesized that, among PLWH who have undetectable HIV viral loads, those with chronic multisite pain (CMP) would have higher levels of circulating pain-related inflammatory markers than those without chronic pain. SETTING: This study was conducted at the University of Alabama at Birmingham's Center for AIDS Research Network of Integrated Clinical System site. METHODS: We compared inflammatory markers in 70 PLWH with CMP and 70 PLWH without chronic pain. Custom multiplex human inflammatory assays were completed on banked plasma specimens to measure cytokines commonly associated with chronic inflammatory pain: interleukin 1β (IL-1β), eotaxin, IL-15, IL-6, tumor necrosis factor α, and leptin. Logistic regression models were built using group status (CMP vs no pain) as the outcome variable, with each cytokine as independent variables and age, sex, substance use, and prescribed opioid medications as covariates. RESULTS: Participants were mostly men (71%); 53% were 50 years or older. The most common sites of pain were low back (86%), hands/feet (81%), and knee (66%). Median CD4 T-cell count was 676 cells per milliliter. IL-1β was significantly higher in the CMP group than in the individuals without chronic pain (odds ratio: 1.35, 95% confidence interval: 1.01 to 1.82, P < 0.05). Eotaxin, IL-15, IL-6, tumor necrosis factor α, and leptin were not significantly different between groups. CONCLUSIONS: We found that PLWH who also have CMP have significantly higher levels of IL-1β than PLWH who do not have any pain. Future work on the role of IL-1β on chronic pain pathogenesis in this population may inform novel approaches to chronic pain management

High Heme and Low Heme Oxygenase-1 Are Associated with Mast Cell Activation/Degranulation in HIV-Induced Chronic Widespread Pain

An overwhelming number of people with HIV (PWH) experience chronic widespread pain (CWP) throughout their lifetimes. Previously, we demonstrated that PWH with CWP have increased hemolysis and attenuated heme oxygenase 1 (HO-1) levels. HO-1 degrades reactive, cell-free heme into antioxidants like biliverdin and carbon monoxide (CO). We found that high heme or low HO-1 caused hyperalgesia in animals, likely through multiple mechanisms. In this study, we hypothesized that high heme or low HO-1 caused mast cell activation/degranulation, resulting in the release of pain mediators like histamine and bradykinin. PWH who self-report CWP were recruited from the University of Alabama at Birmingham HIV clinic. Animal models included HO-1−/− mice and hemolytic mice, where C57BL/6 mice were injected intraperitoneally with phenylhydrazine hydrochloride (PHZ). Results demonstrated that plasma histamine and bradykinin were elevated in PWH with CWP. These pain mediators were also high in HO-1−/− mice and in hemolytic mice. Both in vivo and in vitro (RBL-2H3 mast cells), heme-induced mast cell degranulation was inhibited by treatment with CORM-A1, a CO donor. CORM-A1 also attenuated mechanical and thermal (cold) allodynia in hemolytic mice. Together, the data suggest that mast cell activation secondary to high heme or low HO-1 seen in cells and animals correlates with elevated plasma levels of heme, histamine, and bradykinin in PWH with CWP