Mitochondrial reactivity following acute exposure to experimental pain testing in people with HIV and chronic pain.

Background: Physical stressors can cause a physiological response that can contribute to an increase in mitochondrial dysfunction and Mitochondrial DNA damage (mtDNA damage). People living with HIV (PWH) are more likely to suffer from chronic pain and may be more susceptible to mitochondrial dysfunction following exposure to a stressor. We used Quantitative Sensory Testing (QST) as an acute painful stressor in order to investigate whether PWH with/without chronic pain show differential mitochondrial physiological responses. Methods: The current study included PWH with (n = 26), and without (n = 29), chronic pain. Participants completed a single session that lasted approximately 180 min, including QST. Blood was taken prior to and following the QST battery for assays measuring mtDNA damage, mtDNA copy number, and mtDNA damage-associated molecular pattern (DAMP) levels (i.e., ND1 and ND6). Results: We examined differences between those with and without pain on various indicators of mitochondrial reactivity following exposure to QST. However, only ND6 and mtDNA damage were shown to be statistically significant between pain groups. Conclusion: PWH with chronic pain showed greater mitochondrial reactivity to laboratory stressors. Consequently, PWH and chronic pain may be more susceptible to conditions in which mitochondrial damage/dysfunction play a central role, such as cognitive decline.

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.

Sleep and neighborhood socioeconomic status: a micro longitudinal study of chronic low-back pain and pain-free individuals.

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.

Temporal summation of mechanical pain prospectively predicts movement-evoked pain severity in adults with chronic low back pain.

BACKGROUND: Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire. METHODS: One hundred thirty-four individuals with chronic low back pain were enrolled in this two-session study. During the first study session, temporal summation of mechanical pain and conditioned pain modulation were assessed at the lumbar spine to determine endogenous pain facilitation and inhibition, respectively. One week later, participants returned for a second study session whereby they reported their pain severity and pain interference using the Brief Pain Inventory-Short Form. Movement-evoked pain and physical function capacity were assessed upon completion of the balance, walking, and transition from sit to stand tests of the Short Physical Performance Battery. RESULTS: Temporal summation of mechanical pain, but not conditioned pain modulation, significantly and prospectively predicted greater movement-evoked pain and poorer physical function on the Short Physical Performance Battery. Neither temporal summation nor conditioned pain modulation were significantly related to self-reported pain severity or pain interference on the Brief Pain Inventory-Short Form. CONCLUSIONS: Findings suggest that a pro-nociceptive pain modulatory balance characterized by enhanced pain facilitation may be an important driver of movement-evoked pain severity and poor physical function in individuals with chronic low back pain.

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.

eIF2α phosphorylation controls thermal nociception.

A response to environmental stress is critical to alleviate cellular injury and maintain cellular homeostasis. Eukaryotic initiation factor 2 (eIF2) is a key integrator of cellular stress responses and an important regulator of mRNA translation. Diverse stress signals lead to the phosphorylation of the α subunit of eIF2 (Ser51), resulting in inhibition of global protein synthesis while promoting expression of proteins that mediate cell adaptation to stress. Here we report that eIF2α is instrumental in the control of noxious heat sensation. Mice with decreased eIF2α phosphorylation (eIF2α+/S51A) exhibit reduced responses to noxious heat. Pharmacological attenuation of eIF2α phosphorylation decreases thermal, but not mechanical, pain sensitivity, whereas increasing eIF2α phosphorylation has the opposite effect on thermal nociception. The impact of eIF2α phosphorylation (p-eIF2α) on thermal thresholds is dependent on the transient receptor potential vanilloid 1. Moreover, we show that induction of eIF2α phosphorylation in primary sensory neurons in a chronic inflammation pain model contributes to thermal hypersensitivity. Our results demonstrate that the cellular stress response pathway, mediated via p-eIF2α, represents a mechanism that could be used to alleviate pathological heat sensation.

Sex Differences in Pain.

Females greatly outnumber males as sufferers of chronic pain. Although social and psychological factors certainly play a role in the differences in prevalence and incidence, biological differences in the functioning of the immune system likely underlie these observed effects. This Review examines the current literature on biological sex differences in the functioning of the innate and adaptive immune systems as they relate to pain experience. With rodent models, we and others have observed that male mice utilize microglia in the spinal cord to mediate pain, whereas females preferentially use T cells in a similar manner. The difference can be traced to differences in cell populations, differences in suppression by hormones, and disparate cellular responses in males and females. These sex differences also translate into human cellular responses and may be the mechanism by which the disproportionate chronic pain experience is based. Recognition of the evidence underlying sex differences in pain will guide development of treatments and provide better options for patients that are tailored to their physiology. © 2016 Wiley Periodicals, Inc.

Olfactory exposure to males, including men, causes stress and related analgesia in rodents.

We found that exposure of mice and rats to male but not female experimenters produces pain inhibition. Male-related stimuli induced a robust physiological stress response that results in stress-induced analgesia. This effect could be replicated with T-shirts worn by men, bedding material from gonadally intact and unfamiliar male mammals, and presentation of compounds secreted from the human axilla. Experimenter sex can thus affect apparent baseline responses in behavioral testing.

Spinal dopaminergic projections control the transition to pathological pain plasticity via a D1/D5-mediated mechanism.

The mechanisms that lead to the maintenance of chronic pain states are poorly understood, but their elucidation could lead to new insights into how pain becomes chronic and how it can potentially be reversed. We investigated the role of spinal dorsal horn neurons and descending circuitry in plasticity mediating a transition to pathological pain plasticity suggesting the presence of a chronic pain state using hyperalgesic priming. We found that when dorsal horn neurokinin 1 receptor-positive neurons or descending serotonergic neurons were ablated before hyperalgesic priming, IL-6- and carrageenan-induced mechanical hypersensitivity was impaired, and subsequent prostaglandin E2 (PGE2) response was blunted. However, when these neurons were lesioned after the induction of priming, they had no effect on the PGE2 response, reflecting differential mechanisms driving plasticity in a primed state. In stark contrast, animals with a spinally applied dopaminergic lesion showed intact IL-6- and carrageenan-induced mechanical hypersensitivity, but the subsequent PGE2 injection failed to cause mechanical hypersensitivity. Moreover, ablating spinally projecting dopaminergic neurons after the resolution of the IL-6- or carrageenan-induced response also reversed the maintenance of priming as assessed through mechanical hypersensitivity and the mouse grimace scale. Pharmacological antagonism of spinal dopamine D1/D5 receptors reversed priming, whereas D1/D5 agonists induced mechanical hypersensitivity exclusively in primed mice. Strikingly, engagement of D1/D5 coupled with anisomycin in primed animals reversed a chronic pain state, consistent with reconsolidation-like effects in the spinal dorsal horn. These findings demonstrate a novel role for descending dopaminergic neurons in the maintenance of pathological pain plasticity.

Quantifying blood-spinal cord barrier permeability after peripheral nerve injury in the living mouse.

BACKGROUND: Genetic polymorphisms, gender and age all influence the risk of developing chronic neuropathic pain following peripheral nerve injury (PNI). It is known that there are significant inter-strain differences in pain hypersensitivity in strains of mice after PNI. In response to PNI, one of the earliest events is thought to be the disruption of the blood-spinal cord barrier (BSCB). The study of BSCB integrity after PNI may lead to a better understanding of the mechanisms that contribute to chronic pain. RESULTS: Here we used in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to establish a timecourse for BSCB permeability following PNI, produced by performing a spared nerve injury (SNI). From this longitudinal study, we found that the SNI group had a significant increase in BSCB permeability over time throughout the entire spinal cord. The BSCB opening had a delayed onset and the increase in permeability was transient, returning to control levels just over one day after the surgery. We also examined inter-strain differences in BSCB permeability using five mouse strains (B10, C57BL/6J, CD-1, A/J and BALB/c) that spanned the range of pain hypersensitivity. We found a significant increase in BSCB permeability in the SNI group that was dependent on strain but that did not correlate with the reported strain differences in PNI-induced tactile hypersensitivity. These results were consistent with a previous experiment using Evans Blue dye to independently assess the status of the BSCB permeability. CONCLUSIONS: DCE-MRI provides a sensitive and non-invasive method to follow BSCB permeability in the same group of mice over time. Examining differences between mouse strains, we demonstrated that there is an important genetically-based control of the PNI-induced increase in BSCB permeability and that the critical genetic determinants of BSCB opening after PNI are distinct from those that determine genetic variability in PNI-induced pain hypersensitivity.

A novel investigation of placebo analgesia through social communication in mice.

BACKGROUND AND AIMS: In rodents, placebo analgesia is often investigated through direct conditioning of stimuli, but humans can experience placebo analgesia through expectation without experience. In this study, we sought to determine whether placebo analgesia could be elicited through social communication. METHODS: Male and female mice were housed in pairs (designated "Active" and "Bystander") and tested for thermal thresholds on a hot plate (53 °C). Food restriction (1 hr/day) was implemented. The Active mouse was taken to a new cage with food dusted with cocoa (COC) or cinnamon (CINN). The Bystander mice were given regular chow in the home cage. After feeding, the Active mice were given morphine (5 mg/kg, SC) or saline and tested on the hot plate. After 5 pairings of a flavor and treatment (counterbalanced), Active mice were tested following access to a flavored food. Bystander mice were given their first direct exposure to a flavored food and tested on the hot plate. The protocol was repeated with naloxone (10 mg/kg, IP) administered prior to testing. Finally, mice were tested in a two-choice test with both flavored foods available. RESULTS: Active mice showed a conditioned analgesic response to the morphine-paired flavor that was reduced by naloxone. Bystander mice showed a placebo analgesic response to their cagemate's morphine-paired flavor that was not significantly impacted by naloxone. Bystander mice spent more time in the chamber associated with their cagemate's morphine-paired flavor. CONCLUSIONS: To our knowledge, this is the first investigation of placebo analgesia without direct conditioning, instead relying on social communication between mice. The lack of effect with naloxone pretreatment suggests an opioid-independent effect in the Bystander mice. Placebo analgesia in mice may be possible without direct conditioning to better model the effect of expectation of a novel analgesic in humans.

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.

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 substantial burden at the individual, community, and healthcare 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, depression, and completed brief physical function tasks. In data analytic models, sociodemographic variables were included as covariates. Mediation analyses revealed that emotion regulation mediated the relationship between ACEs and cLBP severity at rest (indirect effect = 0.15 (95% CI [0.06 to 0.25]) and with movement (indirect effect = 1.50 (95% CI [0.69 to 2.57]). Findings suggest ACEs are linked to cLBP severity in adulthood though difficulties in emotion regulation. This aligns with research demonstrating that childhood maltreatment can lead to difficulties in emotion regulation which perpetuate over the lifespan to impact adult health outcomes. 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" (ERASED - ClinicalTrials.gov ID: NCT03338192). PERSPECTIVE: This study presents emotion dysregulation as a psychological pathway through which childhood adversity may contribute to chronic low back pain in adulthood. This work may bolster our understanding of social experiences as risk factors for chronic pain, while identifying targets for clinical intervention.

Coding of facial expressions of pain in the laboratory mouse.

Facial expression is widely used as a measure of pain in infants; whether nonhuman animals display such pain expressions has never been systematically assessed. We developed the mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability; assays involving noxious stimuli of moderate duration are accompanied by facial expressions of pain. This measure of spontaneously emitted pain may provide insight into the subjective pain experience of mice.

Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice.

The innate immune system is increasingly appreciated to play an important role in the mediation of chronic pain, and one molecule implicated in this process is the Toll-like receptor 4 (TLR4). Here, using pharmacological and genetic manipulations, we found that activating TLR4 in the spinal cord, with the agonist lipopolysaccharide (LPS), causes robust mechanical allodynia but only in male mice. Spinal LPS had no pain-producing effect in female mice. TLR4 also has a sex-specific role in inflammatory (complete Freund's adjuvant) and neuropathic (spared nerve injury) pain: pain behaviors were TLR4 dependent in males but TLR4 independent in females. The sex differences appear to be specific to the spinal cord, as LPS administered to the brain or the hindpaw produces equivalent allodynia in both sexes, and specific to pain, as intrathecal LPS produces equivalent hypothermia in both sexes. The involvement of TLR4 in pain behaviors in male mice is dependent on testosterone, as shown by gonadectomy and hormone replacement. We found no sex differences in spinal Tlr4 gene expression at baseline or after LPS, suggesting the existence of parallel spinal pain-processing circuitry in female mice not involving TLR4.

Serotonin-induced hypersensitivity via inhibition of catechol O-methyltransferase activity.

The subcutaneous and systemic injection of serotonin reduces cutaneous and visceral pain thresholds and increases responses to noxious stimuli. Different subtypes of 5-hydroxytryptamine (5-HT) receptors are suggested to be associated with different types of pain responses. Here we show that serotonin also inhibits catechol O-methyltransferase (COMT), an enzyme that contributes to modultion the perception of pain, via non-competitive binding to the site bound by catechol substrates with a binding affinity comparable to the binding affinity of catechol itself (K(i) = 44 µM). Using computational modeling, biochemical tests and cellular assays we show that serotonin actively competes with the methyl donor S-adenosyl-L-methionine (SAM) within the catalytic site. Binding of serotonin to the catalytic site inhibits the access of SAM, thus preventing methylation of COMT substrates. The results of in vivo animal studies show that serotonin-induced pain hypersensitivity in mice is reduced by either SAM pretreatment or by the combined administration of selective antagonists for ß(2)- and ß(3)-adrenergic receptors, which have been previously shown to mediate COMT-dependent pain signaling. Our results suggest that inhibition of COMT via serotonin binding contributes to pain hypersensitivity, providing additional strategies for the treatment of clinical pain conditions.

A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype.

OBJECTIVES: The aim of this study was to assess if genetic variation in the PACE4 (paired amino acid converting enzyme 4) gene Pcsk6 influences the risk for symptomatic knee osteoarthritis (OA). METHODS: Ten PCSK6 single nucleotide polymorphisms were tested for association in a discovery cohort of radiographic knee OA (n=156 asymptomatic and 600 symptomatic cases). Meta-analysis of the minor allele at rs900414 was performed in three additional independent cohorts (total n=674 asymptomatic and 2068 symptomatic). Pcsk6 knockout mice and wild-type C57BL/6 mice were compared in a battery of algesiometric assays, including hypersensitivity in response to intraplantar substance P, pain behaviours in response to intrathecal substance P and pain behaviour in the abdominal constriction test. RESULTS: In the discovery cohort of radiographic knee OA, an intronic single nucleotide polymorphism at rs900414 was significantly associated with symptomatic OA. Replication in three additional cohorts confirmed that the minor allele at rs900414 was consistently increased among asymptomatic compared to symptomatic radiographic knee OA cases in all four cohorts. A fixed-effects meta-analysis yielded an OR=1.35 (95% CI 1.17 to 1.56; p=4.3×10(-5) and no significant between-study heterogeneity). Studies in mice revealed that Pcsk6 knockout mice were significantly protected against pain in a battery of algesiometric assays. CONCLUSIONS: These results suggest that a variant in PCSK6 is strongly associated with protection against pain in knee OA, offering some insight as to why, in the presence of the same structural damage, some individuals develop chronic pain and others are protected. Studies in Pcsk6 null mutant mice further implicate PACE4 in 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.

An improved model of type 2 diabetes with effects on glucose tolerance, neuropathy and retinopathy with and without obesity.

RATIONALE: Type 2 diabetes (T2D) costs billions of dollars annually, is also associated with pain (diabetic neuropathy), as well as retinopathy, lower urinary tract/urinary bladder dysfunction, depression, and systemic inflammation, affecting quality of life for patients. To that end, animal models are utilized to explore potential treatments, but may not reflect the complexity of the condition. OBJECTIVE: We aimed to test an improved model of T2D that more closely mimics the clinical mechanisms and symptoms in an outbred strain of mouse. FINDINGS: Male and female CD-1 mice (n = 72) were fed one of four diets: regular chow (REG), our Standard American Diet (SAD), a revised SAD (SAD2), or the commonly-used high-fat diet (HFD). Overall, HFD- and SAD-fed mice had significant weight gain and increased fat mass. Following injury, the SAD- and SAD2-fed mice showed protracted recovery, but the HFD-fed mice did not. Similarly, SAD- and SAD2-fed mice showed impaired retinal function compared to REG-fed mice, but the HFD-fed mice did not. CONCLUSIONS: The SAD and SAD2 more closely model the problematic dietary intake and subsequent clinical symptoms associated with T2D. POTENTIAL IMPACT OF STUDY: The adjusted SAD2 may be a better representation of a human-translatable diet than the SAD and HFD, and may allow for increased advances in the investigation of T2D-related symptoms.

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.