Tammie L. Quinn

Nonspecific chronic low back pain (NSCLBP) is associated with central sensitization, and both diet quality and epigenetic aging are proposed modifiable, mechanistic contributors to this process. We examined how dietary profiles and epigenetic aging affect central sensitization in NSCLBP. Participants completed dietary, epigenetic aging (DunedinPACE, GrimAge), and central sensitization indicators, including conditioned pain modulation (CPM), heat and mechanical temporal summation (TS), and pain sensitivity questionnaire (PSQ). Dietary profiles were derived from latent profile analysis of dietary inflammatory index components. Nested regression models examined how dietary profiles and epigenetic aging predict central sensitization, adjusting for age, sex, BMI, and race, followed by Benjamini-Hochberg’s false discovery rate correction. We included 200 adults with NSCLBP: mean age 44 years; 62% African American; 55% female; mean BMI 31.33 kg/m². Five tests remained significant after Benjamini-Hochberg correction. DunedinPACE acceleration increased PSQ (β = 2.936, raw p = .034, FDR p = .034), GrimAge acceleration decreased mechanical TS (β = -0.270, raw p = .008, FDR p = .016). Increased low pro-inflammatory diet increased CPM only after accounting for DunedinPACE (β = 49.788, SE = 15.433, raw p = .002, FDR p = .013) and GrimAge (β = 52.685, SE = 15.281, raw p = .001, FDR p = .013). Increased low pro-inflammatory diet decreased heat TS facilitation in the GrimAge-adjusted model (β = -22.028, SE = 8.270, raw p = .009, FDR p = .049). Diet and epigenetic aging jointly, rather than independently, shape central pain processing in NSCLBP, suggesting protective effects of healthier diets.

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.

Chronic low back pain (cLBP) is the most common reason for individual suffering and health care utilization in adults. Ample evidence suggests sociodemographic variables and socioeconomic status (SES) influence pain. However, a framework informing associations on race, SES, and the utilization of pharmacologic therapies and provider type are limited—particularly in cLBP. Thus, this study examined the extent to which sociodemographic (i.e., age, race, and gender) and socioeconomic factors (i.e., national area deprivation index, NADI) influence pain treatment (i.e., NSAIDs, opioids, antidepressants, and non-NSAIDs) and provider utilization for cLBP (i.e., no provider care, primary care, or tertiary care). Eligible participants with cLBP completed a series of questionnaires. Of the 174 participants, 58% were women, 59% were non-Hispanic Black (NHB), and the mean age was 46.10 (SD 13.58). Based on NADI distributions by race, NHB participants lived in more socioeconomically disadvantaged neighborhoods (p < 0.001) than non-Hispanic White (NHW) adults. Results suggested that the use of one or more pharmacologic therapies was associated with race (p = 0.021). Specifically, NHW adults were two times more likely to take one or more pharmacologic therapies than NHBs (p = 0.009). NHWs were also more likely to use NSAIDs (p = 0.041) and antidepressants (p < 0.001) than NHBs. Furthermore, provider utilization was significantly associated with gender (p = 0.037) and age (p = 0.018); which suggests older women were more likely to use primary or tertiary care. Findings from this study expand on the existing literature as it relates to associations between disparities in access to healthcare providers and access to medications. Future research should seek to understand differences in age and utilization of primary or tertiary care providers and continue to examine the influence of sociodemographic and SES factors to cLBP and compare with other types of chronic pain.

Background and Purpose: How the Area Deprivation Index (ADI) performs compared to other measures of socioeconomic status (SES) is unknown. The study purpose is to compare the ADI and other measures of SES in their ability to predict pain severity/interference. Methods: Four measures of SES were compared—ADI, income, education, and subjective social status (SSS). Results: Pain severity/interference correlated positively with ADI (r = .396/r = .33), and negatively with income (r = –.507/r = –.428) and education (r = –.271/r = –.102). Criterion scores of the pain severity model suggest income performs best (AIC = 428.29/BIC = 436.22), followed by ADI (AIC = 437.24/BIC = 445.17), with education performing least well (AIC = 446.35/BIC = 454.29). Similar results were seen for the pain interference model. Conclusions: Neighborhood-level factors warrant consideration along with individual-level factors when attempting to understand the impact of SES on chronic low back pain.

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.