High-impact pain is associated with epigenetic aging among middle-aged and older adults: Findings from the Health and Retirement Study.

BACKGROUND: Chronic pain has been associated with accelerated biological aging, which may be related to epigenetic alterations. We evaluated the association of high-impact pain (i.e., pain that limits activities and function) with epigenetic aging, a measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States. METHODS: Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study (HRS). Epigenetic aging was derived from 13 epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Ordinary least squares regressions were performed to test for differences in the epigenetic clocks, adjusting for the complex survey design, as well as biological, social, and behavioral factors. RESULTS: The analysis consisted of 3,855 adults with mean age of 68.5 years, including 59.8% with no pain and 25.8% with high-impact pain. Consistent with its operational definition, high-impact pain was associated with greater functional and activity limitations. High-impact pain was associated with accelerated epigenetic aging compared to no pain, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. Additionally, GrimAge was accelerated in high-impact pain as compared to low-impact pain. CONCLUSIONS: High-impact pain is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. These findings highlight aging-associated epigenetic alterations in high-impact chronic pain and suggest a potential for epigenetic therapeutic approaches for pain management and the preservation of physical function in older adults.

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.

Socioeconomic Status, Knee Pain, and Epigenetic Aging in Community-Dwelling Middle-to-Older Age Adults.

Chronic musculoskeletal pain is often associated with lower socioeconomic status (SES). SES correlates with psychological and environmental conditions that could contribute to the disproportionate burden of chronic stress. Chronic stress can induce changes in global DNA methylation and gene expression, which increases risk of chronic pain. We aimed to explore the association of epigenetic aging and SES in middle-to-older age individuals with varying degrees of knee pain. Participants completed self-reported pain, a blood draw, and answered demographic questions pertaining to SES. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge) and the subsequent difference of predicted epigenetic age (DNAmGrimAge-Diff). Overall, the mean DNAmGrimAge was 60.3 (±7.6), and the average DNAmGrimAge-diff was 2.4 years (±5.6 years). Those experiencing high-impact pain earned less income and had lower education levels compared to both low-impact and no pain groups. Differences in DNAmGrimAge-diff across pain groups were found, whereby individuals with high-impact pain had accelerated epigenetic aging (∼5 years) compared to low-impact pain and no pain control groups (both ∼1 year). Our main finding was that epigenetic aging mediated the associations of income and education with pain impact, as such the relationship between SES and pain outcomes may occur through potential interactions with the epigenome reflective of accelerated cellular aging. PERSPECTIVE: Socioeconomic status (SES) has previously been implicated in the pain experience. The present manuscript aims to present a potential social-biological link between SES and pain via accelerated epigenetic aging.

Food insecurity is associated with chronic pain and high-impact chronic pain in the USA.

OBJECTIVE: This study evaluated whether food insecurity (US Adult Food Security Survey) was associated with chronic pain (≥ 3 months) and high-impact chronic pain (i.e. pain that limits work and life) among US adults. DESIGN: Cross-sectional analysis. SETTING: Nationally representative sample of non-institutionalised adults in the USA. PARTICIPANTS: 79 686 adults from the National Health Interview Survey (2019-2021). RESULTS: Marginal, low and very low food security were associated with increased prevalence odds of chronic pain (OR: 1·58 (95 % CI 1·44, 1·72), 2·28 (95 % CI 2·06, 2·52) and 3·37 (95 % CI 3·01, 3·78), respectively) and high-impact chronic pain (OR: 1·28 (95 % CI 1·14, 1·42), 1·55 (95 % CI 1·37, 1·75) and 1·90 (95 % CI 1·65, 2·18), respectively) in a dose-response fashion (P-trend < 0·0001 for both), adjusted for sociodemographic, socio-economic and clinically relevant factors. Participation in Supplemental Nutrition Assistance Program (SNAP) and age modified the association between food insecurity and chronic pain. CONCLUSIONS: These findings illustrate the impact of socio-economic factors on chronic pain and suggest that food insecurity may be a social determinant of chronic pain. Further research is needed to better understand the complex relationship between food insecurity and chronic pain and to identify targets for interventions. Moreover, the consideration of food insecurity in the clinical assessment of pain and pain-related conditions among socio-economically disadvantaged adults may be warranted.

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.

A Brief Overview: Sex Differences in Prevalent Chronic Musculoskeletal Conditions.

Musculoskeletal (MSK) pain disorders are some of the most prevalent and disabling chronic pain conditions worldwide. These chronic conditions have a considerable impact on the quality of life of individuals, families, communities, and healthcare systems. Unfortunately, the burden of MSK pain disorders does not fall equally across the sexes. Females consistently demonstrate more prevalent and severe clinical presentations of MSK disorders, and this disparity increases in magnitude with age. The aim of the present article is to review recent studies that have examined sex differences between males and females in four of the most common MSK pain disorders: neck pain, low back pain, osteoarthritis, and rheumatoid arthritis.

Vitamin D Metabolism Genes Are Differentially Methylated in Individuals with Chronic Knee Pain.

INTRODUCTION: Recent evidence suggests that vitamin D may interact with the epigenome and play a role in the pain experience. In order for proper functioning to occur, there must be an adequate level of vitamin D present, made possible by enzymatic reactions that allow vitamin D to be biologically active. The purpose of this study was to explore the epigenetic landscape of genes involved in vitamin D metabolism in individuals with and without chronic knee pain. METHODS: Community-dwelling individuals recruited as part of a larger study focused on knee pain provided demographic, clinical, and pain-related information, as well as an intravenous blood sample to determine DNA methylation levels at CpG sites. RESULTS: There were differences in DNA methylation between those with and without pain in genes that code for enzymes related to vitamin D metabolism: CYP27B1 (1-α-hydroxylase). There was also hypermethylation on the gene that codes for the vitamin D receptor (VDR). CONCLUSIONS: The presence of chronic pain is associated with epigenetic modifications in genes responsible for the expression of enzymes involved in vitamin D metabolism and cellular function. These results lay groundwork in understanding the mechanism underlying the association between vitamin D and chronic pain.

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.

Clinical vitamin D levels are associated with insular volume and inferior temporal gyrus white matter surface area in community-dwelling individuals with knee pain.

Context: Vitamin D is an essential, fat soluble micronutrient long-known for its effects on calcium homeostasis and bone health. With advances in technology, it is being discovered that Vitamin D exerts its effects beyond the musculoskeletal system. Vitamin D has since been noted in nervous system health and functioning, and is becoming a target of interest in brain health, aging, and chronic pain outcomes. Objectives: We and others have previously shown that deficient Vitamin D status is associated with greater pain severity across a variety of conditions, however the reason as to why this relationship exists is still being understood. Here, we sought to examine associations between Vitamin D status and brain structure in those with chronic knee pain. Methods: Structural MRI imaging techniques and whole brain analyses were employed and serum Vitamin D were collected on 140 participants with chronic pain. Covariates included age, sex, race and site, as these data were collected at two separate institutions. ANOVAs using the clinical cut points for Vitamin D status (deficient, insufficient, and optimal) as well as continuous regression-based Vitamin D effects were employed to observe differences in brain volume. P-value was set to 0.017 after correction for multiple comparisons. Results: We discovered that individuals in our sample (age = 50+; 63.6% female; 52.1% Non-Hispanic Black) who were either clinically deficient (<20 ng/mL) or insufficient (20-30 ng/mL) in serum Vitamin D had significant differences in the gray matter of the left circular insular cortex, left inferior temporal gyrus, right middle temporal gyrus, as well as decreased white matter surface area in the right inferior temporal gyrus compared to those considered to have optimal levels (>30 ng/mL) of serum Vitamin D. Conclusion: Evidence from these data suggests that Vitamin D, or lack thereof, may be associated with pain outcomes by mediating changes in regions of the brain known to process and interpret pain. More research understanding this phenomenon as well as the effects of Vitamin D supplementation is warranted.

Epigenetic Aging Mediates the Association between Pain Impact and Brain Aging in Middle to Older Age Individuals with Knee Pain.

Chronic musculoskeletal pain is a health burden that may accelerate the aging process. Accelerated brain aging and epigenetic aging have separately been observed in those with chronic pain. However, it is unknown whether these biological markers of aging are associated with each other in those with chronic pain. We aimed to explore the association of epigenetic aging and brain aging in middle-to-older age individuals with varying degrees of knee pain. Participants (57.91 ± 8.04 y) with low impact knee pain (n = 95), high impact knee pain (n = 53), and pain-free controls (n = 26) completed self-reported pain, a blood draw, and an MRI scan. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge), the subsequent difference of predicted epigenetic and brain age from chronological age (DNAmGrimAge-Difference and Brain-PAD, respectively). There was a significant main effect for pain impact group (F (2,167) = 3.847, P = 0.023, rotational energy = 1/2Iω2 = 0.038, ANCOVA) on Brain-PAD and DNAmGrimAge-difference (F (2,167) = 6.800, P = 0.001, I = mk2 = 0.075, ANCOVA) after controlling for covariates. DNAmGrimAge-Difference and Brain-PAD were modestly correlated (r =0.198; P =0.010). Exploratory analysis revealed that DNAmGrimAge-difference mediated GCPS pain impact, GCPS pain severity, and pain-related disability scores on Brain-PAD. Based upon the current study findings, we suggest that pain could be a driver for accelerated brain aging via epigenome interactions.

Dietary Inflammatory Index (DII) is Associated with Movement-Evoked Pain Severity in Adults with Chronic Low Back Pain: Sociodemographic Differences.

Chronic low back pain (CLBP) is one of the leading causes of pain and disability in adults in the United States and disproportionately burdens non-Hispanic Black (NHB) individuals and females. Approximately 90% of CLBP cases are of unknown cause, and it is imperative that potential causes be explored. It has been reported that diet quality can influence pain state via diet-induced inflammation. The present study assessed the relationship between Dietary Inflammatory Index (DII) and movement evoked-pain severity in people with CLBP and investigated whether race/sex moderated the relationship between DII and movement-evoked pain. Results revealed no significant differences in DII scores between males and females, or between NHB and non-Hispanic White (NHW) participants. Participant sex significantly modified the relationship between DII and movement-evoked pain severity (P = .0155), such that movement-evoked pain severity was significantly impacted by DII scores in females, but not males. Participant race did not significantly moderate the DII - movement-evoked pain severity relationship. These results suggest that diet-induced inflammation may impact the CLBP experiences of females to a greater degree than males. Further research is needed to determine whether dietary interventions that reduce inflammation improve CLBP outcomes and whether these interventions may be differentially-beneficial based on sex. PERSPECTIVE: This article highlights the impact of diet-induced inflammation in a community-based sample as a whole, as well as stratified in various sociodemographic groups. This work expands our understanding of the influence of diet on pain experience and suggests that modifications to diet may be efficacious treatments for reducing chronic pain.

Racial Differences in Pain, Nutrition, and Oxidative Stress.

Investigating the disproportionate rates of chronic pain and their related comorbidities between Black and non-Hispanic White (White) individuals is a growing area of interest, both in the healthcare community and in general society. Researchers have identified racial differences in chronic pain prevalence and severity, but still very little is known about the mechanisms underlying them. Current explanations for these differences have primarily focused on socioeconomic status and unequal healthcare between races as causal factors. Whereas these factors are informative, a racial gap still exists between Black and White individuals when these factors are controlled for. One potential cause of this racial gap in chronic pain is the differences in nutrition and dietary intake between groups. Certain foods play a key role in the inflammatory and oxidative stress pathways in the human body and could potentially influence the severity of the pain experience. Here, we review the previous literature on the surrounding topics and propose a potential mechanism to explain racial differences in the chronic pain population, based on established racial differences in diet and oxidative stress.

Relationship between diet and relative risk of pain in a cross-sectional analysis of the REGARDS longitudinal study.

Aim: Determine if dietary patterns affect risk of pain. Methods: Data from 16,061 participants (55.4% females, 32.3% Black, age 65 ± 9 years) in the REGARDS study were categorized based on the adherence to previous dietary patterns reflecting the prevalent foods within each (convenience, alcohol/salads, plant-based, sweets/fats and 'Southern'). A modified Poisson regression model was used to determine whether dietary patterns were associated with relative risk (RR) of pain. Results: High adherence to 'Southern' dietary pattern was associated with a 41% (95% CI: 23, 61%) increase in RR of pain. High adherence to a plant-based dietary pattern showed a 22% (95% CI: 11, 31%) decrease in the RR of pain. Conclusion: Poor quality dietary patterns increase the RR of pain, while plant-based patterns lowered the RR. Diet patterns should be incorporated into medical history.

Lay abstract Chronic pain is a concern for many people and diet may influence the development and maintenance of pain. It is possible that the types of foods that people consume changes their likelihood of having pain. We know that diet interventions can reduce chronic pain, but it is not known how diet patterns are related to the risk of reporting pain. Here, we examined data from over 16,000 people and looked to see whether the types of foods that they ate was related to the likelihood of reporting pain in the last 4 weeks. People who ate more processed meats, sweetened beverages and fried foods (the 'Southern' diet pattern) were more likely to report pain than those that ate less of these items. However, people whose diet had more plant-based foods (vegetables, fruit, beans) had a decreased risk of reporting pain. Generally, those people who had a higher quality diet were less likely to report pain in the last 4 weeks. Not only can diets be used as a treatment for pain, but eating healthier foods may be protective of developing pain and reduce the likelihood of pain.

Dietary Interventions for Treatment of Chronic Pain: Oxidative Stress and Inflammation.

Chronic pain is highly prevalent in the United States, impacting 28.4% of the adult population, or 69.6 million people, as of 2016. Chronic pain is often associated with anxiety, depression, and restrictions in mobility and daily activities, substantially reducing quality of life. Analgesics, especially opioids, are one of the primary pharmaceutical treatment methods for chronic pain. However, prescription opioid misuse and abuse has become increasingly prevalent and concerning, prompting the need for research into alternative treatment methods which avoid the side effects of traditional treatments. Chronic pain is, in part, thought to be the result of oxidative stress and inflammation, and clinical research has indicated links between these conditions and diet. Thus, dietary interventions are a particularly promising therapeutic treatment for chronic pain, with numerous studies suggesting that diet has a noticeable effect on pain as far down as the cellular level. In this review article, data from a number of clinical trials assessing the effect of three diets-antioxidant-rich, low-carbohydrate, and Mediterranean-on oxidative stress and inflammation is compiled and discussed in the context of chronic pain. Clinical data suggests that low-carbohydrate diets and Mediterranean diets both are especially promising dietary interventions.

Sex and Gender are Not the Same: Why Identity Is Important for People Living with HIV and Chronic Pain.

BACKGROUND: Sex differences in pain sensitivity have been well documented, such that women often report greater sensitivity than men. However, clinical reports highlighting sex differences often equate gender and sex. This is a particularly critical oversight for those whose gender identity is different than their genetic sex. METHODS: This preliminary study sets to analyze differences in pain responses between cisgender and transgender individuals living with HIV and chronic pain. A total of 51 African-American participants (24 cisgender men, 20 cisgender women, 7 transgender women) with similar socioeconomic status were recruited. Genetic sex, gender identity, depression and anxiety, pain severity, pain interference and pain-related stigma were recorded. Participants also completed a quantitative sensory testing battery to assess pain in response to noxious heat and mechanical stimuli. RESULTS: Transgender women and cisgender women demonstrated a greater magnitude of temporal summation for heat pain stimuli or mechanical stimuli compared to cisgender men. Specifically, transgender women reported greater mechanical summation than either cisgender women or cisgender men. Transgender women and cisgender women similarly reported greater chronic pain severity compared to cisgender men. CONCLUSION: These data support the notion that gender identity may play a more significant role in pain sensation than genetic sex. These results further maintain that not only gender identity and genetic sex are distinct variables but that treatment should be based on identity as opposed to genetic sex.

The Effect of Low-Carbohydrate and Low-Fat Diets on Pain in Individuals with Knee Osteoarthritis.

OBJECTIVE: Osteoarthritis is the most prominent form of arthritis, affecting approximately 15% of the population in the United States. Knee osteoarthritis (KOA) has become one of the leading causes of disability in older adults. Besides knee replacement, there are no curative treatments for KOA, so persistent pain is commonly treated with opioids, acetaminophen, and nonsteroidal anti-inflammatory drugs. However, these drugs have many unpleasant side effects, so there is a need for alternative forms of pain management. We sought to test the efficacy of a dietary intervention to reduce KOA. DESIGN: A randomized controlled pilot study to test the efficacy of two dietary interventions. SUBJECTS: Adults 65-75 years of age with KOA. METHODS: Participants were asked to follow one of two dietary interventions (low-carbohydrate [LCD], low-fat [LFD]) or continue to eat as usual (control [CTRL]) over 12 weeks. Functional pain, self-reported pain, quality of life, and depression were assessed every three weeks. Serum from before and after the diet intervention was analyzed for oxidative stress. RESULTS: Over a period of 12 weeks, the LCD reduced pain intensity and unpleasantness in some functional pain tasks, as well as self-reported pain, compared with the LFD and CTRL. The LCD also significantly reduced oxidative stress and the adipokine leptin compared with the LFD and CTRL. Reduction in oxidative stress was related to reduced functional pain. CONCLUSIONS: We present evidence suggesting that oxidative stress may be related to functional pain, and lowering it through our LCD intervention could provide relief from pain and be an opioid alternative.

Intersectional health-related stigma in persons living with HIV and chronic pain: implications for depressive symptoms.

"Intersectional health-related stigma" (IHRS) refers to stigma that arises at the convergence of multiple health conditions. People living with HIV (PLWH) and chronic pain have two highly stigmatized health conditions, and thus may be at especially high risk for internalizing these stigmas and consequently experiencing depression. This study examined the intersectionality of internalized HIV and chronic pain stigma in relation to depressive symptoms in a sample of PLWH and chronic pain. Sixty participants were recruited from an HIV clinic in the Southeastern United States. Chronic pain was defined as pain that has been present for at least three consecutive months, and that has been an ongoing problem for at least half the days in the past six months. All participants completed the HIV Stigma Mechanisms Scale, Internalized Stigma in Chronic Pain Scale, the Short-Form Brief Pain Inventory, and the Center for Epidemiological Studies - Depression Scale. Clinical data was collected from medical records. An intersectional HIV and chronic pain composite variable was created and participants were categorized as either high (28%), moderate (32%), or low (40%). Results revealed that intersectional HIV and chronic pain stigma was significantly associated with severity of depressive symptoms (p = .023). Pairwise contrasts revealed that participants with high (p = .009) and moderate (p = .033) intersectional stigma reported significantly greater mean depressive symptom severity than those with low intersectional stigma. Participants who reported the highest levels of internalized HIV and chronic pain stigma also reported the greatest severity of depressive symptoms. This suggests that the experience of both HIV and chronic pain stigma (i.e., IHRS) among PLWH and chronic pain may synergistically perpetuate negative mood in a more profound manner than experiencing either one stigma alone.

The impact of the Standard American Diet in rats: Effects on behavior, physiology and recovery from inflammatory injury.

BACKGROUND AND AIMS: Obesity is a significant health concern in the Western world and the presence of comorbid conditions suggests an interaction. The overlapping distributions of chronic pain populations and obesity suggests that an interaction may exist. Poor quality diet (high carbohydrates, saturated fats, omega-6 polyunsaturated fatty acids) can lead to increased adiposity which can activate immune cells independent of the activating effect of the diet components themselves. This dual action can contribute to chronic inflammation that may alter susceptibility to chronic pain and prolong recovery from injury. However, traditional examinations of diet focus on high-fat diets that often contain a single source of fat, that is not reflective of an American diet. Thus, we examined the impact of a novel human-relevant (high-carbohydrate) American diet on measures of pain and inflammation in rats, as well as the effect on recovery and immune cell activation. METHODS: We developed a novel, human-relevant Standard American Diet (SAD) to better model the kilocalorie levels and nutrient sources in an American population. Male and female rats were fed the SAD over the course of 20 weeks prior to persistent inflammatory pain induction with Complete Freund's Adjuvant (CFA). Mechanical and thermal sensitivity were measured weekly. Spontaneous pain, open field locomotion and blood glucose levels were measured during diet consumption. Body composition was assessed at 20 weeks. Following full recovery from CFA-induced hypersensitivity, blood was analyzed for inflammatory mediators and spinal cords were immunohistochemically processed for microglial markers. RESULTS: Chronic consumption of the SAD increased fat mass, decreased lean mass and reduce bone mineral density. SAD-fed rats had increased leptin levels and pro-inflammatory cytokines in peripheral blood serum. Following CFA administration, mechanical sensitivity was assessed and recovery was delayed significantly in SAD-fed animals. Sex differences in the impact of the SAD were also observed. The SAD increased body weight and common T-cell related inflammatory mediators in female, but not male, animals. In males, the SAD had a greater effect on bone mineral density and body composition. Long-term consumption of the SAD resulted in elevated microglial staining in the dorsal horn of the spinal cord, but no sex differences were observed. CONCLUSIONS: We demonstrate the negative effects of an American diet on physiology, behavior and recovery from injury. SAD consumption elevated pro-inflammatory mediators and increased microglial activation in the spinal cord. While there were sex differences in weight gain and inflammation, both sexes showed prolonged recovery from injury. IMPLICATIONS: These data suggest that poor quality diet may increase susceptibility to chronic pain due to persistent peripheral and central immune system activation. Furthermore, consumption of a diet that is high in carbohydrates and omega-6 polyunsaturated fatty acid is likely to lead to protracted recovery following trauma or surgical procedures. These data suggest that recovery of a number of patients eating a poor quality diet may be expedited with a change in diet to one that is healthier.