Browsing by Subject "Chronic pain"
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Item 459 Caspase-1 mediated inflammatory response - a critical player in concussive mild traumatic brain injury (mTBI) associated long term pain(Cambridge University Press, 2023-04-24) Nguyen, Tyler; Talley, Sarah; Nguyen, Natalie; Cochran, Ashlyn G.; Al-Juboori, Mohammed; Smith, Jared A.; Saxena, Saahil; Campbell, Edward M.; Obukhov, Alexander G.; White, Fletcher A.; Anesthesia, School of MedicineOBJECTIVES/GOALS: Patients who have experienced conjunctive mild traumatic brain injuries (mTBIs) suffer from a number of comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation after mTBI and its contribution to long-term pain are still poorly understood. METHODS/STUDY POPULATION: Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes and their effects on TBI-related pain. Utilizing a recently developed transgenic caspase-1 luciferase reporter mouse, we characterized the bioluminescence signal evident in both in vivo and ex vivo tissues following repetitive closed head mTBIs. This allowed us to reveal the spatiotemporal dynamics of caspase-1 activation in individual animals over time. Furthermore, we utilize various proteomic and behavioral assays to evaluate the role of caspase-1 mediated inflammation in the development and progression of injury-associated chronic pain. Lastly, by blocking inflammasome caspase-1 activation with a specific inhibitor, we assess its clinical potential as the next therapeutic approach to pain. RESULTS/ANTICIPATED RESULTS: We established that there were significant increases in bioluminescent signals upon protease cleavage in the brain, thorax, abdomen, and paws in vivo, which lasted for at least one week after each injury. Enhanced inflammation was also observed in ex vivo brain slice preparations following injury events that lasted for at least 3 days. Concurrent with the in vivo detection of the bioluminescent signal were persistent decreases in mouse hind paw withdrawal thresholds that lasted for more than two months postinjury. Using MCC950, a potent small molecule inhibitor of NLRP3 inflammasome-caspase 1 activity, we observed reductions in both caspase-1 bioluminescent signals in vivo and caspase-1 p45 expression by immunoblotting and an increase in hind paw withdrawal thresholds. DISCUSSION/SIGNIFICANCE: Overall, these findings suggest that neuroinflammation in the brain following repeated mTBIs is coincidental with a chronic nociplastic pain state, and repeated mTBI-associated events can be ameliorated by a highly specific small molecule inhibitor of NLRP3 inflammasome activation.Item An Analysis of Primary Care Clinician Communication About Risk, Benefits, and Goals Related to Chronic Opioid Therapy(SAGE Publications, 2019-12-10) Danielson, Elizabeth C.; Mazurenko, Olena; Andraka-Christou, Barbara T.; DiIulio, Julie; Downs, Sarah M.; Hurley, Robert W.; Harle, Christopher A.; Health Policy and Management, School of Public HealthBackground. Safe opioid prescribing and effective pain care are particularly important issues in the United States, where decades of widespread opioid prescribing have contributed to high rates of opioid use disorder. Because of the importance of clinician-patient communication in effective pain care and recent initiatives to curb rising opioid overdose deaths, this study sought to understand how clinicians and patients communicate about the risks, benefits, and goals of opioid therapy during primary care visits. Methods. We recruited clinicians and patients from six primary care clinics across three health systems in the Midwest United States. We audio-recorded 30 unique patients currently receiving opioids for chronic noncancer pain from 12 clinicians. We systematically analyzed transcribed, clinic visits to identify emergent themes. Results. Twenty of the 30 patient participants were females. Several patients had multiple pain diagnoses, with the most common diagnoses being osteoarthritis (n = 10), spondylosis (n = 6), and low back pain (n = 5). We identified five themes: 1) communication about individual-level and population-level risks, 2) communication about policies or clinical guidelines related to opioids, 3) communication about the limited effectiveness of opioids for chronic pain conditions, 4) communication about nonopioid therapies for chronic pain, and 5) communication about the goal of the opioid tapering. Conclusions. Clinicians discuss opioid-related risks in varying ways during patient visits, which may differentially affect patient experiences. Our findings may inform the development and use of more standardized approaches to discussing opioids during primary care visits.Item Assessing the use of a clinical decision support tool for pain management in primary care(Oxford University Press, 2022-09-15) Apathy, Nate C.; Sanner, Lindsey; Adams, Meredith C.B.; Mamlin, Burke W.; Grout, Randall W.; Fortin, Saura; Hillstrom, Jennifer; Saha, Amit; Teal, Evgenia; Vest, Joshua R.; Menachemi, Nir; Hurley, Robert W.; Harle, Christopher A.; Mazurenko, Olena; Health Policy and Management, School of Public HealthObjective: Given time constraints, poorly organized information, and complex patients, primary care providers (PCPs) can benefit from clinical decision support (CDS) tools that aggregate and synthesize problem-specific patient information. First, this article describes the design and functionality of a CDS tool for chronic noncancer pain in primary care. Second, we report on the retrospective analysis of real-world usage of the tool in the context of a pragmatic trial. Materials and methods: The tool known as OneSheet was developed using user-centered principles and built in the Epic electronic health record (EHR) of 2 health systems. For each relevant patient, OneSheet presents pertinent information in a single EHR view to assist PCPs in completing guideline-recommended opioid risk mitigation tasks, review previous and current patient treatments, view patient-reported pain, physical function, and pain-related goals. Results: Overall, 69 PCPs accessed OneSheet 2411 times (since November 2020). PCP use of OneSheet varied significantly by provider and was highly skewed (site 1: median accesses per provider: 17 [interquartile range (IQR) 9-32]; site 2: median: 8 [IQR 5-16]). Seven "power users" accounted for 70% of the overall access instances across both sites. OneSheet has been accessed an average of 20 times weekly between the 2 sites. Discussion: Modest OneSheet use was observed relative to the number of eligible patients seen with chronic pain. Conclusions: Organizations implementing CDS tools are likely to see considerable provider-level variation in usage, suggesting that CDS tools may vary in their utility across PCPs, even for the same condition, because of differences in provider and care team workflows.Item Bias in pain care: What patient variables do providers report as influencing their treatment decisions?(2024-10) Rose-McCandlish, Margaret; Hirsh, Adam; Mosher, Catherine; Stewart, JesseRacialized and low socioeconomic status (SES) patients are often under-treated for chronic pain, despite reporting more pain on average. This disparity is likely due to multiple systemic factors, including healthcare provider bias. Providers often treat patients differently for chronic pain depending on the patient’s race and SES, but little is known about providers’ awareness of the extent to which patient demographic variables influence their pain treatment decisions. The present study examined the variables that providers report as influencing their pain treatment decisions, whether these variables group together to form distinct factors, and whether providers who demonstrate racial or socioeconomic bias in their treatment decisions report different patient variables or factors as influencing their treatment decisions compared to providers who did not demonstrate biases. Four hundred thirty-two United States-based physician residents and fellows (“providers”) made treatment decisions for 12 computer-simulated patients with chronic pain who varied by race (Black/White) and SES (high/low). Providers then rated the level to which 15 different variables influenced their treatment decision-making. Robust repeated measures ANOVAs indicated that providers rated patient sex/gender, age, and race as the least influential variables in their pain treatment decisions for the simulated patients. For the factor analysis, I sequentially omitted variables to achieve proper model fit and reliability and arrived at a three-factor solution; I labelled these factors Demographic, Biomedical, and Psychosocial, according to the variables’ conceptual overlap. Robust repeated measures ANOVAs found that reported use of variables did not differ between the providers who demonstrated bias and those who did not demonstrate bias, nor did factor scores for the three factors. The present study suggests that providers have low awareness of the extent to which patient race and SES may influence their clinical decision-making in pain care. Results can help inform future research to improve interventions to reduce the impact of racial and socioeconomic bias on providers’ treatment decisions for patients with chronic pain.Item Brief Report: IL-1β Levels Are Associated With Chronic Multisite Pain in People Living With HIV(Wolters Kluwer, 2017-08-01) Merlin, Jessica S.; Westfall, Andrew O.; Heath, Sonya L.; Goodin, Burel R.; Stewart, Jesse C.; Sorge, Robert E.; Younger, Jarred; Psychology, School of ScienceBACKGROUND: 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.Item Characterizing chronic pain in late adolescence and early adulthood: prescription opioids, marijuana use, obesity, and predictors for greater pain interference(Wolters Kluwer, 2018-11-22) Anastas, Tracy; Colpitts, Kelsey; Ziadni, Maisa; Darnall, Beth D.; Wilson, Anna C.; Psychology, School of ScienceIntroduction: Chronic pain in late adolescence and young adults is understudied and poorly characterized. Objectives: We sought to characterize key variables that may impact pain interference in late adolescents and young adults with chronic pain, including prescription opioid use, marijuana use, psychological symptoms, and obesity. Methods: Retrospective, cross-sectional medical chart review for patients aged 17 to 23 years (N = 283; 61% Females) seeking care at a tertiary care pain clinic. Data on pain characteristics, health behaviors, and mental health distress were examined, in addition to self-reported pain intensity and interference. Results: Overlapping pain conditions were common in this young adult sample (mean ≥ 2 pain conditions). Back pain was the most commonly cited pain condition, and the majority of pain was of unknown etiology. Results revealed high rates for current opioid prescription, overweight or obese status, and mental health problems. Those using prescription opioids were more likely to endorse tobacco use and had greater pain interference. Importantly, the presence of mental health distress and opioid use were predictive of higher levels of pain-related interference. Conclusion: Treatment-seeking adolescents and young adults with chronic pain evidence complex care needs that include pain and mental comorbidities, as well as risky health behaviors. Pain and mental health distress were associated with poorer physical health, opioid prescription and marijuana use, and pain-related interference. Findings underscore the need for additional research on pain, treatment patterns, and health behaviors and their impact on developmental trajectories, as well as the need to develop and apply effective early interventions in this at-risk population.Item Characterizing mechanism-based pain phenotypes in patients with chronic pancreatitis: a cross-sectional analysis of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies(Wolters Kluwer, 2023) Saloman, Jami L.; Conwell, Darwin L.; Fogel, Evan; Vege, Santhi Swaroop; Li, Liang; Li, Shuang; Andersen, Dana K.; Fisher, William E.; Forsmark, Christopher E.; Hart, Phil A.; Pandol, Stephen J.; Park, Walter G.; Evans Phillips, Anna; Topazian, Mark; Van Den Eeden, Stephen K.; Serrano, Jose; Yadav, Dhiraj; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer; Medicine, School of MedicinePain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N = 681) with CP, 80% experienced abdominal pain within the year before enrollment. Subjects who experienced pain in the week before enrollment (N = 391) completed PROMIS Neuropathic and Nociceptive Pain Quality instruments which were then used to classify them by pain type: 40% had nociceptive, 5% had neuropathic-like, and 32% had both types of pain. The prevalence of having both types of pain was higher among women and subjects with diabetes mellitus, whereas nociceptive-only pain was more prevalent among men and those with pancreatic duct stricture. Other factors, including pain medication use and healthcare utilization, did not differ between groups based on pain type. Subjects in the Both group had significantly worse health and QoL scores relative to those with nociceptive-only pain, suggesting that using psychosocial pain surveys may be useful for understanding pain subtypes in patients with CP. Additional research is needed to identify biochemical and biophysical signatures that may associate with and predict responses to mechanism-specific interventions.Item Child pain-related injustice appraisals mediate the relationship between just-world beliefs and pain-related functioning(Wiley, 2021) Daenen, Frederick; McParland, Joanna; Baert, Fleur; Miller, Megan Marie; Hirsh, Adam Todd; Vervoort, Tine; Psychology, School of ScienceBackground: Research among adult and paediatric samples suggests that pain-related injustice appraisals contribute to adverse pain-related functioning. However, a singular focus on pain-related injustice appraisals carries the risk of underestimating the role of broader concepts of justice. This study examined the unique roles of child pain-related injustice appraisals and just-world beliefs in understanding disability and physical, emotional, social and academic functioning, as well as the mediating role of injustice appraisals in the relationship between just-world beliefs and functioning. Methods: Participants comprised a school sample of 2,174 children (Study 1) and a clinical sample of 146 paediatric chronic pain patients (Study 2) who completed the Injustice Experience Questionnaire (IEQ), Personal and General Belief in a Just World scales (JWB-P/G), Functional Disability Inventory (FDI), Pain Catastrophizing Scale for Children (PCS-C) and Pediatric Quality of Life Inventory (PEDSQL). Results: For both samples, child pain-related injustice appraisals were associated with poorer functioning, after controlling for just-world beliefs, catastrophizing, pain intensity, age and sex. In the school sample, injustice appraisals mediated the associations of both personal and general just-world beliefs with functioning. In the clinical sample, injustice appraisals mediated the association of personal, but not general, just-world beliefs with all functioning scales. Conclusions: The current findings attest to the unique role of pain-related injustice appraisals in understanding child pain-related functioning and their explanatory value in understanding the relationship between fundamental just-world beliefs and child pain-related functioning. Significance: The present study adds to emerging literature on the adverse effects of child pain-related injustice appraisals in the context of pain, through showing that pain-related injustice appraisals are uniquely associated with pain-related functioning and mediate the relationship between just-world beliefs and pain-related functioning. These findings suggest that interventions may target pain-related injustice appraisals as a mechanism for change in children.Item Clinical and Quality of Life Benefits for End-Stage Workers' Compensation Chronic Pain Claimants following H-Wave® Device Stimulation: A Retrospective Observational Study with Mean 2-Year Follow-Up(MDPI, 2023-02-01) Trinh, Alan; Williamson, Tyler K.; Han, David; Hazlewood, Jeffrey E.; Norwood, Stephen M.; Gupta, Ashim; Medicine, School of MedicinePreviously promising short-term H-Wave® device stimulation (HWDS) outcomes prompted this retrospective cohort study of the longer-term effects on legacy workers’ compensation chronic pain claimants. A detailed chart-review of 157 consecutive claimants undergoing a 30-day HWDS trial (single pain management practice) from February 2018 to November 2019 compiled data on pain, restoration of function, quality of life (QoL), and polypharmacy reduction into a summary spreadsheet for an independent statistical analysis. Non-beneficial trials in 64 (40.8%) ended HWDS use, while 19 (12.1%) trial success charts lacked adequate data for assessing critical outcomes. Of the 74 final treatment study group charts, missing data points were removed for a statistical analysis. Pain chronicity was 7.8 years with 21.6 ± 12.2 months mean follow-up. Mean pain reduction was 35%, with 89% reporting functional improvement. Opioid consumption decreased in 48.8% of users and 41.5% completely stopped; polypharmacy decreased in 36.8% and 24.4% stopped. Zero adverse events were reported and those who still worked usually continued working. An overall positive experience occurred in 66.2% (p < 0.0001), while longer chronicity portended the risk of trial or treatment failure. Positive outcomes in reducing pain, opioid/polypharmacy, and anxiety/depression, while improving function/QoL, occurred in these challenging chronic pain injury claimants.Item Clinical Characterization of Juvenile Fibromyalgia in a Multicenter Cohort of Adolescents Enrolled in a Randomized Clinical Trial(Wiley, 2023) Lynch-Jordan, Anne M.; Connelly, Mark; Guite, Jessica W.; King, Christopher; Goldstein-Leever, Alana; Logan, Deirdre E.; Nelson, Sarah; Stinson, Jennifer N.; Ting, Tracy V.; Wakefield, Emily O.; Williams, Amy E.; Williams, Sara E.; Kashikar-Zuck, Susmita; Fibromyalgia Integrative Training for Teens Clinical Trial Study Group; Childhood Arthritis and Rheumatology Research Alliance Pain Workgroup Investigators; Psychiatry, School of MedicineObjective: Juvenile fibromyalgia (JFM) is a complex chronic pain condition that remains poorly understood. The study aimed to expand the clinical characterization of JFM in a large representative sample of adolescents with JFM and identify psychological factors that predict pain interference. Methods: Participants were 203 adolescents (ages 12-17 years) who completed baseline assessments for the multisite Fibromyalgia Integrative Training for Teens (FIT Teens) randomized control trial. Participants completed the Pain and Symptom Assessment Tool, which includes a Widespread Pain Index (WPI; 0-18 pain locations) and Symptom Severity checklist of associated somatic symptoms (SS; 0-12) based on the 2010 American College of Rheumatology criteria for fibromyalgia. Participants also completed self-report measures of pain intensity, functional impairment, and psychological functioning. Results: Participants endorsed a median of 11 painful body sites (WPI score) and had a median SS score of 9. Fatigue and nonrestorative sleep were prominent features and rated as moderate to severe by 85% of participants. Additionally, neurologic, autonomic, gastroenterologic, and psychological symptoms were frequently endorsed. The WPI score was significantly correlated with pain intensity and catastrophizing, while SS scores were associated with pain intensity and all domains of physical and psychological functioning. Depressive symptoms, fatigue, and pain catastrophizing predicted severity of pain impairment. Conclusion: JFM is characterized by chronic widespread pain with fatigue, nonrestorative sleep, and other somatic symptoms. However, how diffusely pain is distributed appears less important to clinical outcomes and impairment than other somatic and psychological factors, highlighting the need for a broader approach to the assessment and treatment of JFM.