Chronic Pain Resilience Across Clinical Populations: A Concept Analysis.

BACKGROUND: Chronic pain resilience is a concept that is frequently used in research but lacks theoretical clarity. Understanding chronic pain resilience is germane to developing interventions to improve it and the overall quality of life among individuals with chronic pain. AIMS: To uncover and clarify the unique characteristics of the concept of chronic pain resilience. DESIGN: A concept analysis using Rodgers' evolutionary method. METHODS: Full-text articles published after 2000 in English were used to inform the concept analysis. Scopus, PubMed, PsychINFO, Embase, and CINAHL Plus with Full Text were utilized for literature searches. Rodgers' evolutionary approach was used to clarify the attributes, antecedents, and consequences. RESULTS: The search yielded 31 articles that were used in the analysis. The key attributes of chronic pain resilience included engagement in meaningful activities despite pain, maintaining positive psychological homeostasis, buffering against negative mental outcomes, seeking support, and self-empowerment. After considering surrogate terms, antecedents, attributes, and consequences, chronic pain resilience may be defined as the development of the capacity to successfully adapt to chronic pain. This adaptation results in a move toward optimal social, physical, mental, and behavioral functioning by balancing negative and positive psychosocial factors, despite the additional challenges brought about by living with chronic pain.

Adverse Childhood Experiences and Chronic Low Back Pain in Adulthood: The Role of Emotion Regulation.

Chronic low back pain (cLBP) is characterized by biopsychosocial determinants that collectively result in a substantial burden at the individual, community, and health care system levels. A growing body of literature suggests that childhood adversity is longitudinally associated with the development and maintenance of various chronic pain conditions in adulthood. Little research has investigated the psychological processes that might underlie the association between adverse childhood experiences (ACEs) and cLBP. Emotion regulation comprises a substantive part of the subjective experience of pain and may be a potential mechanism through which ACEs contribute to cLBP etiology and maintenance. Thus, the current study examined the extent to which emotion dysregulation mediated the relationship between ACEs and pain severity (pain at rest and movement-evoked pain) in adults with cLBP. Participants included 183 adults (53.0% female, 62.5% non-Hispanic Black) between the ages of 18 and 85 with cLBP. Participants self-reported on ACEs, pain, difficulties in emotion regulation (DER), depression, and completed brief physical function tasks. In data analytic models, sociodemographic variables were included as covariates. Analyses revealed that emotion regulation mediated the relationship between ACEs and cLBP severity at rest (indirect effect = .15 [95% CI {.06-.25}]) and with movement (indirect effect = 1.50 [95% CI {.69-2.57}]). Findings suggest ACEs are linked to cLBP severity in adulthood through DER. This aligns with research demonstrating that childhood maltreatment can lead to DER, which perpetuate over the lifespan to impact adult health outcomes. PERSPECTIVE: This study presents emotion dysregulation as a psychological pathway through which childhood adversity may contribute to cLBP in adulthood. This work may bolster our understanding of social experiences as risk factors for chronic pain, while identifying targets for clinical intervention. TRIAL REGISTRATION: This study utilized baseline data collected as part of a parent trial titled "Examining Racial and SocioEconomic Disparities in Chronic Low Back Pain" (ClinicalTrials.gov ID: NCT03338192).

Race-specific associations: inflammatory mediators and chronic low back pain.

ABSTRACT: Chronic low back pain (cLBP) is a global health crisis that disproportionately burdens non-Hispanic Black (NHB) individuals, compared with those who identify as non-Hispanic White (NHW). Despite the growing personal and societal impact of cLBP, its biological underpinnings remain poorly understood. To elucidate the biological factors that underlie the racial disparities in cLBP, this study sought to determine whether inflammatory mediators associated with pain interference (PI), pain at rest (PAR), and movement-evoked pain (MEP) differ as a function of racial identity. Blood samples were collected from 156 individuals with cLBP (n = 98 NHB participants, n = 58 NHW participants). Enzyme-linked immunosorbent assay and multiplex assays were used to quantify concentrations of proinflammatory (fibrinogen, C-reactive protein [CRP], serum amyloid A, tumor necrosis factor α [TNF-α], and interleukin [IL]-1α, IL-1ß, and IL-6) and anti-inflammatory markers (IL-4 and IL-13). Spearman rho correlations were used to assess associations among markers of inflammation and PI, PAR, and MEP using the Brief Pain Inventory-Short Form. Analyses revealed that for NHW patients, CRP, serum amyloid A, and IL-6 were positively associated with cLBP outcomes and IL-4 was inversely associated with PAR and MEP. However, for NHB patients, only IL-1α was positively associated with PAR. Our findings suggest that, while there are associations between inflammation and cLBP outcomes, the biomarkers that underlie the inflammation could very well differ as a function of racialized minority group. However, more research with racially inclusive samples is needed to elucidate the mechanisms that may contribute to racial disparities in cLBP.

The Pace of Biological Aging Predicts Nonspecific Chronic Low Back Pain Severity.

This study aimed to determine if and how the pace of biological aging was associated with nonspecific chronic low back pain (cLBP) and compare what measure of epigenetic age acceleration most strongly predicts cLBP outcomes. We used the Dunedin Pace of Aging from the Epigenome (DunedinPACE), Horvath's, Hannum's, and PhenoAge clocks to determine the pace of biological aging in 69 cLBP, and 49 pain-free controls (PFCs) adults, ages 18 to 85 years. On average, participants with cLBP had higher DunedinPACE (P < .001) but lower Horvath (P = .04) and Hannum (P = .02) accelerated epigenetic age than PFCs. There was no significant difference in PhenoAge acceleration between the cLBP and PFC groups (P = .97). DunedinPACE had the largest effect size (Cohen's d = .78) on group differences. In univariate regressions, a unit increase in DunedinPACE score was associated with 265.98 times higher odds of cLBP than the PFC group (P < .001). After controlling for sex, race, and body mass index (BMI), the odds ratio of cLBP to PFC group was 149.62 (P < .001). Furthermore, among participants with cLBP, DunedinPACE scores positively correlated with pain severity (rs = .385, P = .001) and interference (rs = .338, P = .005). Epigenetic age acceleration from Horvath, Hannum, and PhenoAge clocks were not significant predictors of cLBP. The odds of a faster pace of biological aging are higher among adults with cLBP, and this was associated with greater pain severity and disability. Future interventions to slow the pace of biological aging may improve cLBP outcomes. PERSPECTIVE: Accelerated epigenetic aging is common among adults with nonspecific cLBP. Higher DunedinPACE scores positively correlate with pain severity and interference, and better predict cLBP than other DNA methylation clocks. Interventions to slow the pace of biological aging may be viable targets for improving pain outcomes.

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's 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 < .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.

Neighborhood Environment and Epigenetic Age: A Scoping Review.

BACKGROUND: Interest in how the neighborhood environment impacts age-related health conditions has been increasing for decades. Epigenetic changes are environmentally derived modifications to the genome that alter the way genes function-thus altering health status. Epigenetic age, a biomarker for biological age, has been shown to be a useful predictor of several age-related health conditions. Consequently, its relation to the neighborhood environment has been the focus of a growing body of literature. OBJECTIVE: We aimed to describe the scope of the evidence on the relationship between neighborhood environmental characteristics and epigenetic age. METHODS: Using scoping review following methods established by Arksey and O'Malley, we first defined our research questions and searched the literature in PubMed, PsycINFO, and EMBASE. Next, we selected the literature to be included, and finally, we analyzed and summarized the information. RESULTS: Nine articles met the inclusion criteria. Most studies examined deprivation as the neighborhood characteristic of interest. While all studies were observational in design, the articles included diverse participants, including men and women, adults and children, and multiple ethnicities. Results demonstrated a relationship between the neighborhood environment and epigenetic age, whether the characteristic of interest is socioeconomic or physical. CONCLUSIONS: Overall, studies concluded there was a relationship between neighborhood characteristics and epigenetic age, whether the characteristic of interest was socioeconomic or physical. However, findings varied based on how the neighborhood characteristic and/or epigenetic age was measured. Furthermore, a paucity of investigations on physical characteristics was noticeable and warrants increased attention.

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.

Epigenetic age acceleration mediates the relationship between neighborhood deprivation and pain severity in adults with or at risk for knee osteoarthritis pain.

An estimated 250 million people worldwide suffer from knee osteoarthritis (KOA), with older adults having greater risk. Like other age-related diseases, residents of high-deprivation neighborhoods experience worse KOA pain outcomes compared to their more affluent neighbors. The purpose of this study was to examine the relationship between neighborhood deprivation and pain severity in KOA and the influence of epigenetic age acceleration (EpAA) on that relationship. The sample of 128 participants was mostly female (60.9%), approximately half non-Hispanic Black (49.2%), and had a mean age of 58 years. Spearman bivariate correlations revealed that pain severity positively correlated with EpAA (ρ = 0.47, p ≤ 0.001) and neighborhood deprivation (ρ = 0.25, p = 0.004). We found a positive significant relationship between neighborhood deprivation and EpAA (ρ = 0.47, p ≤ 0.001). Results indicate a mediating relationship between neighborhood deprivation (predictor), EpAA (mediator), and pain severity (outcome variable). There was a significant indirect effect of neighborhood deprivation on pain severity through EpAA, as the mediator accounted for a moderate portion of the total effect, PM = 0.44. Epigenetic age acceleration may act as a mechanism through which neighborhood deprivation leads to worse KOA pain outcomes and may play a role in the well-documented relationship between the neighborhood of residence and age-related diseases.

Evaluating the Utilization of a Perioperative Hyperglycemic Protocol: A Quality Improvement Project.

PURPOSE: The purpose of this project to evaluate adherence to the perioperative hyperglycemic protocol among Certified Registered Nurse Anesthetists (CRNAs) at a large academic hospital. A secondary objective of this project is CRNAs' perceptions of barriers to point-of-care (POC) testing and the protocol. DESIGN: A quality improvement project. METHODS: Using Donabedian's conceptual framework, a Phase 1 retrospective chart analysis of 297 patients with diabetes undergoing noncardiac surgery before and after implementing POC testing for intraoperative glucose control was performed. Only patients with preoperative BG ≥ 180 mg/dL were included in this phase of the project, which involved a comparison of the protocol utilization before and after implementation of POC testing. Phase 2 included an assessment of CRNA's perceptions of the protocol. FINDINGS: The final sample included 91 (37 preimplementation; 54 postimplementation) participants. There were no significant demographic differences between the groups. Overall, 52.7% of patients had intraoperative glucose checks, and only 16.5% received insulin. Preoperative BG levels decreased 11.4-points, and postoperative BG levels increased 20.4 points when comparing pre- and postimplementation groups. However, there were significant differences in postoperative glucose levels, pre- and postimplementation. The survey showed that the majority (65.5%) of CRNAs identified difficulty locating the protocol as the primary barrier to utilization. CONCLUSIONS: Although all patients included in this project qualified for an intraoperative glucose check, findings revealed that only half of the patients had a glucose check and less than one fifth of the patients received insulin treatment, indicating poor adherence to the protocol. Thus, while implementing protocols is essential, utilization and adherence to the protocol are critical to improving patient outcomes. Recommendations for continued improvement include increasing protocol accessibility, staff training, compliance monitoring, and a more simple protocol structure.

A Systematic Review of Race, Sex, and Socioeconomic Status Differences in Postoperative Pain and Pain Management.

PURPOSE: Optimal postoperative pain management remains a significant problem despite the availability of multiple preoperative, intraoperative, and postoperative pain management interventions. Recent studies suggest that racialized minorities, female sex, and individuals of lower socioeconomic status (SES) are more likely to experience more severe pain and inadequate pain management postoperatively. Our systematic review aimed to determine race, sex, and SES differences in postoperative pain and postoperative pain management. DESIGN: This study is a systematic review of literature. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we systematically searched 5 databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Embase, Scopus, and Cochrane. We included primary source peer-reviewed articles published after 1990 that measured postoperative pain and race/ethnicity, sex/gender, or SES, which were published in English. Two pairs of reviewers independently screened each title, abstract, and article for inclusion. In cases of disagreement, a third reviewer broke the tie. FINDINGS: A total of 464 articles were screened, of which 32 were included in this study. In most studies, Blacks/African American experience more severe postoperative pain than Whites/Caucasians. Whites were more likely to be prescribed opioids for pain management than Blacks, Hispanics, and Asians. Also, individuals of lower SES and females reported more postoperative pain. One study found no race/ethnic group differences in pain scores and opioid use after the implementation of the enhanced recovery after surgery (ERAS) protocol. CONCLUSIONS: Optimal postoperative pain relief continues to be a challenge for individuals who self-identify as racialized minorities, females, and those of lower SES. Standardization of care may help reduce disparities in postoperative pain management.

Improving Communication Between ICU Nurses and Anesthesia Providers Using a Standardized Handoff Protocol.

PURPOSE: This quality improvement (QI) project aimed to improve handoff communication between intensive care unit (ICU) nurses and anesthesia providers using a standardized preoperative handoff protocol for nonemergent and noncardiac procedures. DESIGN: A quality improvement project. METHODS: Following project approval, the project team provided staff education regarding a pre-populated handoff tool from the electronic medical record (EMR) adapted for perioperative use. In addition, the project team assessed the providers' perception and satisfaction with handoff communication before and after the intervention. FINDINGS: Of the 128 transfers, 76% completed the handoff tool during the 1-month implementation phase. CRNAs (n = 60), Registered Nurses (RNs; n = 88), and anesthesia residents (n = 30) completed the pre-and post-implementation surveys. Pre-implementation, 40% of providers were dissatisfied with communication, and only 14% reported dissatisfaction post-implementation. Also, 40% of providers believed this handoff protocol increased the amount of accurate information shared during reports without delaying the transition of care. CONCLUSIONS: The standardized handoff tool appears to improve information sharing during the transfer of care and improve provider satisfaction with the handoff process. Long term, it may reduce adverse patient events and improve outcomes. Use of a pre-populated handoff tool from the EMR provides a cost-effective solution to decrease erroneous reporting by removing human error associated with the recall.

The applications of cryoneurolysis for acute and chronic pain management.

BACKGROUND: Cryoneurolysis is a term used to describe the application of extreme cold to targeted nerve tissue. The primary goal of the application of a thermal neurolytic technique is to disrupt the conduction of pain signals from the periphery to the central nervous system and eliminate or diminish the experience of pain. Recent advancements in ultrasound technology coupled with the development and approval of handheld devices specifically designed to deliver cryoneurolysis has expanded the use of this modality in the perioperative setting. APPLICATION: Surgical procedures including total knee arthroplasties, shoulder arthroplasties, thoracotomies, and mastectomies have all demonstrated long-term pain relief benefits when cryoneurolysis has been administered days to weeks prior to the planned procedure. In addition, the newly designed handheld device allows for office-based clinical use and has been utilized for various chronic pain conditions including neuropathic and phantom limb pain. CONCLUSION: The evidence clearly demonstrates that cryoneurolysis has a low risk profile and when administered appropriately, provides prolonged analgesia without promoting motor blockade. This narrative review article describes the unique mechanism of action of cryoneurolysis for prolonged pain relief and provides emerging evidence to support its applications in both acute and chronic pain management.

Racial Differences in 25-Hydroxy Vitamin D and Self-Reported Pain Severity in a Sample of Individuals Living with Non-Specific Chronic Low Back Pain.

Introduction: Considerable evidence suggests that there are significant ethnic/racial differences in the experience of pain among individuals suffering from chronic musculoskeletal conditions. Additionally, low levels of vitamin D have been associated with pain severity. Further, vitamin D deficiency is more prevalent in Non-Hispanic Black (NHB) individuals compared to Non-Hispanic Whites (NHW). Objective: The aim of this study was to investigate the associations among race, pain severity, and serum levels of vitamin D in a sample of patients with chronic low back pain (cLBP). Methods: All study participants (n = 155) self-identified their race/ethnicity as either NHB or NHW. Blood samples were collected to assess circulating levels of serum 25- hydroxy vitamin D. Vitamin D levels were categorized as optimal (≥20 ng/mL), insufficient (12-19 ng/mL) or deficient (<12 ng/mL). Participants then self-reported their pain severity using the Brief Pain Inventory - Short Form. Results: Results showed that a greater proportion of NHB versus NHW participants were categorized as Vitamin D deficient (χ 2 (2, N = 155) = 16.79, p < 0.001). An analysis of covariance (ANCOVA) revealed that NHBs reported significantly greater pain severity relative to NHWs (F(1150) = 6.45) p = 0.012. Further, self-reported pain severity significantly differed according to Vitamin D clinical categories (F(2150) = 4.19, p = 0.013). Participants with deficient vitamin D reported significantly greater pain severity in comparison to participants with optimal vitamin D (F(1101) = 7.28, p = 0.008). Conclusion: The findings suggest that Vitamin D deficiency may be linked to greater pain severity in a sample of individuals with cLBP, especially for those who identify as NHB.

Genome-wide DNA methylation study identifies significant epigenomic changes associated with internalized stigma in adults with non-specific chronic low back pain.

Non-specific chronic low back pain (cLBP) represents a common musculoskeletal condition with no identifiable cause. It cannot be diagnosed with conventional neuroimaging techniques such as computerized tomography (CT). The diagnostic uncertainty that characterizes non-specific cLBP can lead to stigmatizing responses from others that can become internalized Among individuals with non-specific cLBP, internalized stigma is associated with greater pain intensity and disability. Yet, no study has examined the biological mechanism linking high internalized stigma to worse outcomes in individuals with non-specific cLBP. We aimed to identify differentially methylated loci (DML), enrichment pathways, and associated network interactions among individuals with non-specific cLBP experiencing low vs. high internalized stigma. We examined DNA methylation in whole blood samples from 48 adults, ages 19-85, using reduced representation bisulfite sequencing (RRBS). After controlling for age, sex, race, and multiple testing, differentially methylated loci (DML) differed in adults with low vs. high internalized stigma by at least 10% and q < 0.01 in 3,665 CpG sites: 2,280 hypomethylated and 1,385 hypermethylated. Gene ontology (GO) analyses of the annotated genes from these sites revealed significant enrichment of 274 biological processes, 29 cellular components, and 24 molecular functions (adjusted p < 0.05). The top enriched molecular functions regulate protein binding and DNA binding of transcription factor activity. Pathway analyses indicated that many functional genomic pathways, including Hippo Signaling, Melanogenesis, and Pathways in Cancer, were enriched with differentially methylated genes. Also, there was a significant interaction between relevance pathways such as P53, mTOR, PI3K-Akt, and Wnt signaling pathways. These pathways have previously been associated with neuroinflammation, neurodegeneration, and stress-related conditions. Thus, findings point to possible stress-induced DNAm changes as the link between high levels of internalized stigma and worse outcomes in adults with non-specific cLBP.

Rediscovery of Methadone to Improve Outcomes in Pain Management.

Clinically, methadone is most known for its use in the treatment of opioid maintenance therapy. However, methadone's pharmacological profile makes it an excellent analgesic that can enhance acute and chronic pain management. It is a potent µ-receptor agonist with a longer elimination half-life than most clinically used opioids. In addition, methadone inhibits serotonin and norepinephrine uptake, and it is an N-methyl-D-aspartate antagonist. These distinct analgesic pathways mediate hyperalgesic, allodynic, and neuropathic pain. Its unique analgesic properties provide several essential benefits in perioperative use, neuropathic pain, cancer, and noncancer pain. Despite these proven clinical utilities, methadone has not been used widely to treat acute and chronic pain in opioid naïve patients. This article describes the unique pharmacology of methadone and provides emerging evidence to support its application in acute and chronic pain management. Pain management options and guidelines for surgical patients on methadone are discussed as well.

Confronting Racism in All Forms of Pain Research: Reframing Study Designs.

This second paper in a 3-part series on antiracism in pain research across the translational spectrum focuses on study design factors. Although objectivity is a cornerstone value of science, subjectivity is embedded in every step of the research process as investigators make choices about who they collaborate with, which research questions they ask, how they recruit participants, which research tools they use, and how they analyze and interpret data. We present theory and evidence from disciplines such as sociology, medical anthropology, statistics, and public health to discuss 4 common study design factors, including 1) the dominant biomedical narrative of pain that restricts funding and exploration of social indicators of pain, 2) low diversity and inclusion in pain research enrollment that restricts generalizability to racialized groups, 3) the use of "race" or "ethnicity" as a statistical variable and proxy for lived experiences (eg, racism, resilience), and 4) limited modeling in preclinical research for the impact of social factors on pain physiology. The information presented in this article is intended to start conversations across stakeholders in the pain field to explore how we can come together to adopt antiracism practices in our work at large to achieve equity for racialized groups. PERSPECTIVE: This is the second paper in a 3-part series on antiracism in pain research. This part identifies common study design factors that risk hindering progress toward pain care equity. We suggest reframes using an antiracism framework for these factors to encourage all pain investigators to collectively make strides toward equity.

Translation of Credentialing Examination for Providers with English as a Second Language: An Exploratory Study.

Racial and ethnic minorities disproportionately suffer the burden of adverse health outcomes in the United States. Increasing the diversity of healthcare providers may help decrease disparities in outcomes. Unfortunately, language barriers may affect performance in nursing school and credentialing examinations. The purpose of this exploratory study was to identify current practices and trends affecting the translation of credentialing examinations. Commissioned by the National Board of Certification and Recertification for Nurse Anesthetists, a survey was sent to the credentialing organizations soliciting information about their exam translation practices and considerations. Among the 27 credentialing organizations (two licensure and 25 certification organizations) that completed the survey, 63% were from healthcare. All the organizations offered their credentialing examinations in English. Some offered their examination in Chinese/Mandarin (15%), Spanish (11%), French (7%), and Arabic (7%). The majority (78%) do not translate their examinations into another language. Among the six credentialing organizations translating their examinations, 67% translate one, and 17% translate two examinations. Most use the forward and back-translation techniques. For organizations embarking on a multilingual credentialing program, it is imperative to ensure psychometric equivalence of their examinations. Translation can help ensure that candidates are tested on their intended competencies, not their language proficiency.

Epigenome-wide DNA methylation profiling of conditioned pain modulation in individuals with non-specific chronic low back pain.

BACKGROUND: The pathoanatomic cause of chronic low back pain (cLBP) cannot be identified for up to 90% of individuals. However, dysfunctional processing of endogenous nociceptive input, measured as conditioned pain modulation (CPM), has been associated with cLBP and may involve changes in neuronal gene expression. Epigenetic-induced changes such as DNA methylation (DNAm) have been associated with cLBP. METHODS: In the present study, the relationship between CPM and DNAm changes in a sample of community-dwelling adults with nonspecific cLBP (n = 48) and pain-free controls (PFC; n = 50) was examined using reduced representation bisulfite sequencing. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to identify key pathways involved in efficient versus deficient CPM. RESULTS: Based on CPM efficiency, we identified 6006 and 18,305 differentially methylated CpG sites (DMCs) with q values < 0.01 among individuals with cLBP and PFCs, respectively. Most of the DMCs were hypomethylated and annotated to genes of relevance to pain, including OPRM1, ADRB2, CACNA2D3, GNA12, LPL, NAXD, and ASPHD1. In both cLBP and PFC groups, the DMCs annotated genes enriched many GO terms relevant to pain processing, including transcription regulation by RNA polymerase II, nervous system development, generation of neurons, neuron differentiation, and neurogenesis. Both groups also enriched the pathways involved in Rap1-signaling, cancer, and dopaminergic neurogenesis. However, MAPK-Ras signaling pathways were enriched in the cLBP, not the PFC group. CONCLUSIONS: This is the first study to investigate the genome-scale DNA methylation profiles of CPM phenotype in adults with cLBP and PFCs. Based on CPM efficiency, fewer DMC enrichment pathways were unique to the cLBP than the PFCs group. Our results suggest that epigenetically induced modification of neuronal development/differentiation pathways may affect CPM efficiency, suggesting novel potential therapeutic targets for central sensitization. However, CPM efficiency and the experience of nonspecific cLBP may be independent. Further mechanistic studies are required to confirm the relationship between CPM, central sensitization, and nonspecific cLBP.