Millions of Americans present to the emergency department (ED) annually after motor vehicle collision (MVC), and more than 90% are discharged to home after evaluation. To date, the association between prior exposure to stressful life events and acute pain reported at the time of presentation has not been examined. Data for this analysis were obtained from an ongoing, prospective cohort study of African Americans (current n = 898) ≥18 and <65 years of age who presented to the ED within 24 hours of MVC. Exclusion criteria included hospital admission after evaluation and long bone fracture. Previous burden of adverse life events was assessed at 6-week follow-up using the Life Events Checklist for DSM-4 (LEC). Exposure to each event was defined to include the options "happened to me," "witnessed it," and "learned about it." The association between previous life stress and acute pain outcomes in the ED was assessed via linear regression, adjusting for age, sex, study site, and experiences of discrimination. Greater exposure to stressful life events prior to MVC was associated with increased acute pain (evaluated via a 0-10 NRS) in the ED (β = 0.103, p = 0.023). Further studies are needed to understand the influence of past trauma on acute stress exposure. Supported by NIAMS R01AR060852.

Chronic widespread pain (CWP) and posttraumatic stress disorder (PTSD) are frequent sequelae of trauma that occur at different rates in women and men. We sought to identify microRNA (miRNA) that may contribute to sex-dependent differences in vulnerability to these outcomes using in silico and human data. Monte Carlo simulations identified miRNA in which predicted targeting of CWP or PTSD genes was most enriched (p < 0.05). One miRNA in this group, miR-19b was of particular interest as it has been shown to be 1) under the transcriptional control of Estrogen Receptor alpha 2) up-regulated following stress exposure in relevant CNS regions. The association between miR-19b expression (identified via small RNA sequencing) assessed in blood samples (PAXgene RNA tubes, n = 67) collected in the emergency department in the immediate aftermath of motor vehicle collision (MVC) and the presence of CWP (ACR definition) and PTSD (Impact of Events Scale-Revised > 33) at 6 months was assessed using logistic regression analysis. Initial miR-19b expression levels predicted both CWP (β=1.06, p=0.018) and PTSD (β=1.32, p=0.012) outcomes 6 months following MVC. In addition, a significant interaction between miR-19b and sex was observed (p = 0.029 for CWP and 0.018 for PTSD) such that low levels of miR-19b expression predicted CWP and PTSD in women and high expression predicted these outcomes in men. Predicted targets of miR-19b include circadian rhythm genes CLOCK, RORA, and NPAS2. We are currently testing whether miR-19b directly binds these targets using in vitro assays. Together, our results highlight the sex-dependent expression of miR-19b in humans and suggest that miR-19b might play a pathogenic role in CWP and PTSD following MVC trauma.

Approximately four million Americans present to the emergency department (ED) each year after motor vehicle collision (MVC). More than 90% of these individuals have acute musculoskeletal strain only and are discharged to home after evaluation. Acute musculoskeletal pain (MSP) at the time of ED evaluation is the norm in this population; the intensity of such MSP varies widely between individuals for reasons that remain poorly understood. In this study we used structural equation modeling (SEM) to test the hypothesis that sociodemographic characteristics and stress-induced vulnerability influence acute MSP severity in the early aftermath of MVC. European Americans 18-65 years of age presenting to one of eight EDs within 24 hours of MVC who did not have fracture or other injury requiring hospital admission were enrolled (n = 948). Participants completed an ED interview, which assessed demographic characteristics, pain (0-10 NRS) in each body region, pre-MVC somatic and depressive symptoms, crash characteristics, pre-MVC physical health, trait anger, and life threat. Significant causal predictors of the latent variable "stress-induced pain vulnerability" included smoking status (p=0.006), sex (p<0.001), education (p=0.024), and the presence of an FK506 binding protein 5 vulnerability allele (p=0.016). Significant causal predictors of the latent variable "acute pain" included sex (p=0.01), smoking status (p=0.023), education (p=0.009), number of body regions struck (p<0.001), life threat (p<0.001), and stress-induced vulnerability (p=0.03). The model testing the influence of "stress-induced pain vulnerability" on "acute pain" yielded χ2=1047, p<0.001, CFI/TLI =0.97/0.96 and RMSEA= 0.03, indicating a good model fit. These results suggest that stress-induced pain vulnerability influences acute pain severity after MVC and identify a number of factors that contribute to stress-induced pain vulnerability and to the intensity of acute pain after MVC. Funding by NIAMS R01AR056328.

More than four million patients present to U.S. Emergency Departments (EDs) each year after motor vehicle collision (MVC). Over 90% of these individuals have acute musculoskeletal pain (MSP), and, while less than 5% have a fracture or require hospital admission, 20-30% transition to persistent MSP. Individuals presenting to the ED with acute MSP after MVC do not receive risk-stratified care, however in other settings providing stratified physiotherapy and psychological interventions for acute MSP has been shown to improve outcomes and reduce costs.1 The goal of this study was to characterize health resource utilization according to persistent axial MSP (PAMSP) risk among individuals presenting to the ED after MVC. Data for this analysis was obtained from a large prospective cohort of 948 European Americans who presented to the ED after MVC and were discharged home after evaluation. Participants were categorized as being at low, medium, or high risk of PAMSP using data obtained at the baseline ED visit and a previously developed tool. Pain outcomes and medication and health service use were assessed at six week follow-up (obtained in 859/948 (91%)), PAMSP at six weeks was present in 63 (24%), 134 (50%), and 206 (78%) of those categorized from ED data as being at low, medium, and high risk of PAMSP, respectively. At six week follow-up, only 17 (6%) of those at high risk of PAMSP had seen a mental health provider and only 123 (46%) had received any sort of manual therapy. Use of opioid sparing agents was very low (e.g., gabapentin (16 [4%]) and SNRIs (7 [2%]). These data indicate that health services utilization among individuals with acute MSP after MVC is poorly stratified. Further studies are needed to determine if stratified interventions could improve outcomes and/or reduce costs. (1. Hill et al., Lancet, 2011.) Supported by NIAMS R01AR056328.

Inadequate pain treatment in U.S. emergency departments (ED) is common, in part because of the limited and idiosyncratic use of opioids by emergency providers. In a previous study of European Americans (EA, n=690) experiencing acute musculoskeletal pain (MSP) after motor vehicle collision,1 we found a strong inverse relationship between educational status and receipt of opioid medication in the ED. In this study, we repeated the same analysis in a sister cohort of African Americans (AA). Data for this analysis were obtained from an ongoing, prospective cohort study of African Americans (current n=691) who presented to the ED within 24 hours of motor vehicle collision and were discharged to home after evaluation. Patients with long bone fracture were excluded. Consistent with findings in our European American cohort, the majority of study participants in our ongoing African American study had moderate or severe pain (636/691 [92%]), and more educated patients reported lower levels of pain (p<0.001). However, the strong inverse relationship between educational attainment and opioid administration observed in European Americans was absent in the African American cohort. Although frequency of opioid administration was lower among patients with postgraduate educations (7/26 [27%] of AA, 9/87 [10%] of EA) compared to patients who did not complete high school (21/59 [36%] of AA, 15/28 [54%] of EA), opioid receipt did not differ significantly across educational attainment strata (χ2 test p=0.757). When educational attainment, age, sex, acute pain severity in the ED, and income were included as independent variables in a logistic regression model assessing opioid receipt, pain severity was the only significant predictor (p=0.002). Further studies are needed to better understand racial/ethnic differences in the relationship between patient educational attainment and receipt of opioid medication. (1. Platts-Mills, et al., PAIN, 2012.) Supported by NIAMS R01AR060852.

More than four million Americans present to U.S. Emergency Departments (EDs) each year after motor vehicle collision (MVC). More than 90% of these individuals have acute musculoskeletal pain (MSP), and, while less than 5% have a fracture or require hospital admission, 20-30% transition to chronic MSP. Individuals with acute MSP after MVC are most often discharged with oral non-steroidal anti-inflammatory drugs (NSAIDs) or opioid medications, however optimal medication treatments are poorly defined and the influence of acute medication choices on post-MVC pain trajectory are unknown. In this study we evaluated the effect of opioid versus NSAID medication treatment at the time of ED discharge on the presence of moderate or severe MSP (MSMSP, NRS > 3) six weeks after MVC. Data was obtained from a large prospective cohort of adult European Americans (n=948) who presented to the ED after MVC. Propensity score matched analysis was used to compare the odds of MSMSP at six week follow-up (obtained in 859/948 (91%) among patients discharged with opioid analgesics alone (198/859 (23%)) vs. those discharged with NSAIDs alone (338/859 (39%)). Participants were propensity-matched on demographic and clinical characteristics, baseline pain scores, and MVC characteristics. At 6-weeks, 49% of those receiving NSAIDS and 56% of those receiving opioids reported MSMSP. After propensity matching, there was no significant difference in MSMSP at six weeks between those discharged with opioids vs. those discharged with NSAIDS (OR=0.92; 95% CI 0.33 – 1.51). These results suggest that initial ED provider choice of NSAIDs versus opioid medication at discharge following MVC does not influence the development of MSMSP six weeks after MVC. Supported by NIAMS R01AR056328.

Defining the optimal use of opioid medications for pain treatment and understanding individual factors that affect opioid prescribing for pain are of intense interest to both policymakers and providers. Recent research suggests cognitive factors such as pain catastrophizing may influence opioid prescribing. In this study we examined the relationship between pain catastrophizing and receipt of opioid medication for pain among European American patients seen in the emergency department (ED) after motor vehicle collision (MVC). Patients 18-65 years of age who presented to the ED within 24 hours of MVC and were discharged to home after evaluation (n = 948) were enrolled. ED evaluation included an assessment of pain catastrophizing (Pain Catastrophizing Scale) overall pain severity (0-10 NRS), and sociodemographic characteristics. Overall pain severity at six-week follow-up was also assessed. Logistic regression analyses were used to evaluate the association between pain catastrophizing and opioid medication receipt in the ED and at six-week follow-up. After adjusting for study site, sex, age, and education, pain catastrophizing predicted receipt of opioid medication in the ED (p<0.001). This association did not remain significant after adjusting for acute pain severity in the ED (p=0.10). After removing education from the regression model, pain catastrophizing became marginally significant (p=0.06). Six-week follow-up was obtained from 859 participants (91%). Pain catastrophizing was associated with reported opioid use at six weeks after controlling for site, sex, age, and education but was not significant after adjusting for six-week pain severity (p=0.21). Together this data suggests that pain catastrophizing after a traumatic experience influences opioid administration but is not an independent predictor in this population after adjustment for pain severity. Supported by NIAMS R01AR056328.

To date, most studies of chronic musculoskeletal pain (CMP) development after trauma/stress exposure have focused on pain symptoms alone or the association of CMP with one or two other outcomes. In contrast, individuals often experience post-traumatic pain symptoms as part of a broader constellation of psychological and somatic symptoms. In this study we evaluated how trajectories of pain symptoms, depressive symptoms, posttraumatic stress disorder (PTSD) symptoms, and somatic symptoms (often termed “post-concussive” (PC)) cluster over time after motor vehicle collision (MVC) in a large cohort of adult European Americans who presented to the ED within 24 hours of MVC. Study participants were interviewed in the ED at the time of initial presentation and six weeks, six months, and one year following MVC. Outcome evaluations at each timepoint included an assessment of pain (0-10 NRS, Regional Pain Scale), depressive symptoms (CES-D), PTSD symptoms (IES-R), and PC symptoms (Rivermead Questionnaire). Follow-up assessments of enrolled patients (n = 948) were completed in 859 (91%), 840 (89%), and 861 (91%) participants at six weeks, six months, and one year, respectively. Exploratory factor analysis identified four correlated factors (PTSD, depressive, pain, and somatic symptoms) with high internal consistency and reliability and consistent structure over time. Individual trajectories for each factor were estimated, and K-means cluster analysis performed using trajectory intercepts found that a 4-cluster solution provided the best fit to the data. These four clusters were: globally resilient; mildly symptomatic with symptoms of depression and PTSD more prominent; extreme symptoms across all four categories with somatic and pain symptoms somewhat more prominent; and mild somatic symptoms with pain, depressive, and PTSD symptoms. These results indicate that CMP after MVC do not develop in isolation, and identify several common patterns of somatic and psychological symptoms associated with post-MVC CMP. Supported by NIAMS R01AR056328.

Peritraumatic distress symptoms and subsequent posttraumatic stress disorder (PTSD) symptoms after motor vehicle collision (MVC) have been proposed to promote the development of MVC-related neck pain (MRNP) via a number of mechanisms. We used a path analysis model to evaluate longitudinal associations between peritraumatic distress symptom clusters (life threat, helplessness/anger, loss of control, and guilt/shame, assessed in the emergency department (ED) using the Peritraumatic Distress Inventory), PTSD symptom clusters (avoidance, intrusion/re-experiencing, and hyperarousal, assessed 6 weeks, 6 months, and one year after MVC using the Impact of Events Scale-Revised (IES-R)), and MRNP severity (assessed via 0-10 NRS at each timepoint). Of note, patients reporting neck pain at any timepoint were asked whether their pain was MVC-related; only MRNP was included in analyses. Analyses were performed in Mplus using data from a prospective cohort study of European Americans (n = 948) who presented to the ED within 24 hours of MVC and were discharged to home. ED evaluation was performed via in-person interview and follow-up interviews were performed via telephone interview or internet-based questionnaire. Confirmatory factor analyses of distress and IES-R subscales indicated acceptable fits to the data (RMSEA/CFI of 0.084/0.933 and 0.051/0.958 respectively). Overall fit of the longitudinal model of relationships between distress and PTSD subscales and MRNP was excellent (RMSEA = 0.049 [90% CI 0.036 to 0.052] in trimmed model). Peritraumatic helplessness/anger in the ED predicted 6 week MRNP severity (β = .148, p < 0.0001). Six week and six month PTSD hyperarousal symptoms, but not avoidance or intrusion symptoms, partially mediated the relationship between MRNP at six weeks and six months and between MRNP at six months and one year, respectively. These results support the hypothesis that stress-related psychological symptoms contribute to/mark vulnerability to persistent MRNP after MVC. Supported by NIAMS R01AR056328.

Evidence suggests that body mass index (BMI) may influence the risk of an individual transitioning from acute to chronic musculoskeletal pain. In this study we evaluated the influence of BMI on risk of developing persistent moderate or severe musculoskeletal neck pain (MSMNP) 6 months after a motor vehicle collision (MVC). European Americans age ≥18 and <65 years presenting to the emergency department (ED) within 24 hours of MVC and discharged to home after ED evaluation were enrolled. Participant's height and weight data, collected via ED interview, were used to calculate BMI. BMI categories (underweight, normal, overweight, and obese) were defined using standard CDC cut-offs. Neck pain (0-10 NRS) was assessed in the ED via in-person interview and at 6 month follow-up via telephone interview or web-based questionnaire. NRS score ≥4 was defined as MSMNP. Participants reporting pain at 6 month follow-up were asked if the pain was MVC-related and only MVC-related pain was included in the data analyses. Height and weight data was available for 934/948 (99%) of enrolled ED patients, and 840/948 (89%) completed 6 month follow-up evaluation. While BMI was not associated with acute neck pain severity (F=0.389 p=0.76), baseline BMI category predicted persistent MSMNP 6 months after MVC (4/16 (25%)) underweight [RR vs. normal weight 1.4 [95%CI 0.6-3.4], 52/293 (18%) normal weight, 47/252 (19%) overweight (RR 1.1, 95%CI [0.7-1.5]), and 69/250 (28%) obese individuals (RR 1.6, 95%CI [1.1-2.3]), (χ2=9.3, p=0.025). These results remained essentially unchanged after adjusting for age and sex. In addition, obese individuals reported a greater number of body regions with persistent MVC-related pain at 6 months (2.01 vs. 2.55, F=4.25, p=0.04). BMI category alone was a poor predictor of persistent MSMNP presence vs. absence (AUROCC=0.565), indicating that weight status is a significant but non-deterministic predictor of MSMNP outcome. Supported by NIAMS R01AR056328.

Over four million adults present to US emergency departments (EDs) each year after motor vehicle collision (MVC); the great majority of these individuals are discharged to home after ED evaluation. A subset of these individuals develops chronic MVC-related widespread pain (CMWP). Typical trajectories by which individuals develop this morbid outcome (e.g. progressive extension of pain vs. early development with non-recovery) are unknown. We evaluated trajectories of pain extent in a large cohort of adult European Americans who presented to the ED within 24 hours of MVC. Study participants were interviewed in the ED at the time of initial presentation and six weeks, six months, and one year following MVC. Evaluation at each time point included an assessment of pain (0-10 NRS) in nineteen body regions. If pain in a body region was reported, the MVC-relatedness of the pain was assessed. Widespread pain (WP) was defined as MVC-related pain in ≥7 body regions. One year after MVC, 75/948 (9%) of enrolled participants had CMWP. Among this group, almost half (45.3%) had WP in the ED. WP at 6 weeks and 6 months were present in 67.6% and 54.9% of these participants, respectively. Trajectory analyses of extent of pain across time (performed via SAS PROC TRAJ) for the entire cohort (n=948) identified 8.7% of participants with pain distributions over time consistent with a trajectory of initial WP in the ED and non-recovery across time. Together these data support the hypothesis that most individuals developing CMWP after MVC develop early WP that does not remit and suggest that individuals developing CMWP after MVC could be identified in the early post-MVC period and targeted for early preventive interventions. Supported by NIAMS R01AR056328. Over four million adults present to US emergency departments (EDs) each year after motor vehicle collision (MVC); the great majority of these individuals are discharged to home after ED evaluation. A subset of these individuals develops chronic MVC-related widespread pain (CMWP). Typical trajectories by which individuals develop this morbid outcome (e.g. progressive extension of pain vs. early development with non-recovery) are unknown. We evaluated trajectories of pain extent in a large cohort of adult European Americans who presented to the ED within 24 hours of MVC. Study participants were interviewed in the ED at the time of initial presentation and six weeks, six months, and one year following MVC. Evaluation at each time point included an assessment of pain (0-10 NRS) in nineteen body regions. If pain in a body region was reported, the MVC-relatedness of the pain was assessed. Widespread pain (WP) was defined as MVC-related pain in ≥7 body regions. One year after MVC, 75/948 (9%) of enrolled participants had CMWP. Among this group, almost half (45.3%) had WP in the ED. WP at 6 weeks and 6 months were present in 67.6% and 54.9% of these participants, respectively. Trajectory analyses of extent of pain across time (performed via SAS PROC TRAJ) for the entire cohort (n=948) identified 8.7% of participants with pain distributions over time consistent with a trajectory of initial WP in the ED and non-recovery across time. Together these data support the hypothesis that most individuals developing CMWP after MVC develop early WP that does not remit and suggest that individuals developing CMWP after MVC could be identified in the early post-MVC period and targeted for early preventive interventions. Supported by NIAMS R01AR056328.

DNA methylation at CpG dinucleotides is an important epigenetic mechanism regulating gene expression. Loci of variable DNA methylation often correlate with regulatory DNA regions controlling gene transcription. Identifying such regions that are differentially methylated between individuals who do and do not develop chronic widespread pain (CWP) after motor vehicle collision (MVC) may provide insights into pathogenic mechanisms of CWP. In this nested case-control pilot study we used the Illumina HumanMethylation450k platform to assess DNA methylation across the entire genome between individuals who did and did not develop CWP after MVC. Analyses were performed using data from a prospective cohort study of 948 European Americans who presented to the emergency department (ED) within 24 hours of MVC. DNA was procured from patient blood samples obtained while in the ED. Follow-up assessments of reported pain by body region were performed at 6 weeks, 6, and 12 months. Eleven females with CWP (≥7 body regions with pain at 6 weeks, 6 months and/or 1 year) were selected and age-matched to 11 female controls with no or mild regional pain. After controlling for false discovery rate (<5%), the Bartlett test for variance comparison identified 310 variably methylated CpG loci, mapped to 254 genes. We then identified loci with interquartile range difference between groups of at least 10% and used the Ingenuity Pathway Analysis software to identify overrepresented pathways in this list of variably methylated genes. The antigen presentation pathway (HLA-DMB, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-F, and CALR genes), nuclear factor of activated T-cells (NFAT) pathway, and chemokine CXCR4 signaling pathway were among the top five overrepresented pathways (overlap p-values 6.8E-05, 4.8E-04, and 2.9E-03, correspondingly). Our preliminary results suggest that variable methylation in genes responsible for immune response may be a risk factor for the development of chronic musculoskeletal pain after MVC. Supported by NIAMS R01AR056328. DNA methylation at CpG dinucleotides is an important epigenetic mechanism regulating gene expression. Loci of variable DNA methylation often correlate with regulatory DNA regions controlling gene transcription. Identifying such regions that are differentially methylated between individuals who do and do not develop chronic widespread pain (CWP) after motor vehicle collision (MVC) may provide insights into pathogenic mechanisms of CWP. In this nested case-control pilot study we used the Illumina HumanMethylation450k platform to assess DNA methylation across the entire genome between individuals who did and did not develop CWP after MVC. Analyses were performed using data from a prospective cohort study of 948 European Americans who presented to the emergency department (ED) within 24 hours of MVC. DNA was procured from patient blood samples obtained while in the ED. Follow-up assessments of reported pain by body region were performed at 6 weeks, 6, and 12 months. Eleven females with CWP (≥7 body regions with pain at 6 weeks, 6 months and/or 1 year) were selected and age-matched to 11 female controls with no or mild regional pain. After controlling for false discovery rate (<5%), the Bartlett test for variance comparison identified 310 variably methylated CpG loci, mapped to 254 genes. We then identified loci with interquartile range difference between groups of at least 10% and used the Ingenuity Pathway Analysis software to identify overrepresented pathways in this list of variably methylated genes. The antigen presentation pathway (HLA-DMB, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-F, and CALR genes), nuclear factor of activated T-cells (NFAT) pathway, and chemokine CXCR4 signaling pathway were among the top five overrepresented pathways (overlap p-values 6.8E-05, 4.8E-04, and 2.9E-03, correspondingly). Our preliminary results suggest that variable methylation in genes responsible for immune response may be a risk factor for the development of chronic musculoskeletal pain after MVC. Supported by NIAMS R01AR056328.

Negative expectations have been found to be powerful predictors of adverse pain outcomes. Individual characteristics associated with negative recovery expectations may provide useful clues regarding the potential etiology of such expectations; however, to date, no studies have evaluated the association between individual characteristics and recovery expectations after motor vehicle collision (MVC). In this study, we evaluated characteristics associated with negative recovery expectations in a large cohort of European Americans ≥18 and < 65 years of age who presented to the emergency department (ED) within 24 hours of MVC. Exclusion criteria included hospital admission after ED evaluation. Enrolled patients completed an ED interview which assessed recovery expectations: certainty of recovery, estimated time to physical recovery (ETPR) and estimated time to emotional recovery (ETER). Consistent with previous studies, individuals uncertain of recovery (UOR, 267/948, 28%), those with longer ETPR (>2 weeks, 263/948, 30%), and those with longer ETER (>4 weeks, 341/948, 45%) had substantially worse outcomes (e.g., each recovery expectation predicted moderate/severe neck pain and posttraumatic stress disorder at 6 months at p < 0.0001 level). Bivariate analyses assessed the relationship of each recovery expectation with sociodemographic factors, pre-MVC physical and mental health factors, MVC characteristics, and post-MVC psychological and somatic symptoms. A number of factors across each of these domains were associated with each expectation, with the exception of MVC-related characteristics, which were generally poorly associated with recovery expectations. Backwards stepwise logistic regression modeling (pin=0.10, pout=0.15) using factors associated at p<0.05 in bivariate analyses yielded sets of characteristics associated with certainty of recovery, ETPR, and ETER. Each of these models contained multiple potential modifiable risk factors. Results of bivariate and multivariate analyses will be presented at the conference. Supported by NIAMS R01AR056328.

Millions of Americans present to the emergency department (ED) each year after motor vehicle collision (MVC); more than 90% are discharged to home after ED evaluation. Acute musculoskeletal pain (MSP) is the norm in these individuals, and 20-40% transition to chronic MSP, most commonly in the axial region (neck/shoulders, back). ED-based risk stratification tools have been developed for a variety of clinical conditions and are a necessary for the development and testing of ED-based preventive interventions for high risk individuals. No ED-based risk stratification tools are currently available for chronic post-MVC axial MSP (CPAM). We developed a risk stratification tool for CPAM, using data from a prospective multisite longitudinal study of individuals evaluated 6 weeks, 6 months, and 1 year after MVC (n=860). CPAM, defined by the presence of MVC-related MSP ≥4 (on 0-10 NRS) in one or more axial body regions 6 weeks and 6 and/or 12 months after MVC, was present in 303/860 (35%). Bivariate analyses identified 26 candidate predictor variables; logistic regression with backward selection was then applied to these candidate predictors in 1000 bootstrap samples. The top five predictors selected in >90% of bootstrap samples and retained in the final prediction model were: patient age, severity of neck pain in the ED, severity of overall pain in ED, belief regarding whether other driver was at fault, and estimated time to physical recovery. The model showed excellent calibration (slope=1.00) and good discrimination between those who develop chronic axial pain and those who do not (AUC=0.76). Cut-off scores with different sensitivity and specificity were generated; specific cut-off score for ED-based preventive intervention studies for high risk individuals can be selected based on the intensity and risks of the intervention. Validation of this predictive tool and further optimization are needed in future prospective studies. Supported by NIAMS R01AR056328.

Catechol-O-methyltransferase, encoded by the COMT gene, is the primary enzyme that metabolizes catecholamines. COMT haplotypes have been associated with vulnerability to persistent atraumatic pain. In this prospective observational study, we investigated the influence of COMT on persistent pain and pain interference with life functions after motor vehicle collision (MVC). 948 European American adults who presented to the emergency department (ED) within 24 hours of MVC were enrolled. Six week telephone follow-up evaluation included an assessment of overall pain (0-10 numeric rating scale) and pain interference (Brief Pain Inventory scales). Ten SNPs spanning the COMT gene were successfully genotyped, eight were present in three haploblocks: block 1 (rs2020917, rs737865, rs1544325), block 2 (rs4633, rs4818, rs4680) and block 3 (rs174697, rs165599). After adjustment for multiple comparisons, haplotype T-C-G from block 1 predicted decreased pain interference (p =.0038): Homozygous individuals had lower scores (11.4±2.3) than heterozygotes or those without this haplotype (19.2±1.0 and 16.5±0.9, respectively). The pain-protective effect of the low pain sensitivity (LPS, C-G-G) haplotype from the second block was only observed if at least one T-C-G haplotype was present in the first block (haplotype × haplotype interaction p=.001 and .0007 for pain and pain interference, respectively). In these individuals (n=410/859, 48%), each copy of the LPS allele was associated with the reduction of pain by 0.8±0.3 units (p=.002) and interference by 5.7±1.6 units (p=.0004). Haplotype A-G from the third block was associated with pain and interference in males only (sex × haplotype interaction p=.007 and <.001, respectively). These results suggest that genetic variants in different functional regions of COMT gene predict persistent pain and pain interference after MVC, and that this effect is the result of interaction between loci. Funded by NIH 1R01AR056328. Catechol-O-methyltransferase, encoded by the COMT gene, is the primary enzyme that metabolizes catecholamines. COMT haplotypes have been associated with vulnerability to persistent atraumatic pain. In this prospective observational study, we investigated the influence of COMT on persistent pain and pain interference with life functions after motor vehicle collision (MVC). 948 European American adults who presented to the emergency department (ED) within 24 hours of MVC were enrolled. Six week telephone follow-up evaluation included an assessment of overall pain (0-10 numeric rating scale) and pain interference (Brief Pain Inventory scales). Ten SNPs spanning the COMT gene were successfully genotyped, eight were present in three haploblocks: block 1 (rs2020917, rs737865, rs1544325), block 2 (rs4633, rs4818, rs4680) and block 3 (rs174697, rs165599). After adjustment for multiple comparisons, haplotype T-C-G from block 1 predicted decreased pain interference (p =.0038): Homozygous individuals had lower scores (11.4±2.3) than heterozygotes or those without this haplotype (19.2±1.0 and 16.5±0.9, respectively). The pain-protective effect of the low pain sensitivity (LPS, C-G-G) haplotype from the second block was only observed if at least one T-C-G haplotype was present in the first block (haplotype × haplotype interaction p=.001 and .0007 for pain and pain interference, respectively). In these individuals (n=410/859, 48%), each copy of the LPS allele was associated with the reduction of pain by 0.8±0.3 units (p=.002) and interference by 5.7±1.6 units (p=.0004). Haplotype A-G from the third block was associated with pain and interference in males only (sex × haplotype interaction p=.007 and <.001, respectively). These results suggest that genetic variants in different functional regions of COMT gene predict persistent pain and pain interference after MVC, and that this effect is the result of interaction between loci. Funded by NIH 1R01AR056328.

Persistent moderate or severe neck pain (MSNP) after motor vehicle collision (MVC) is an international public health problem. Increasing evidence suggests that the etiology of persistent pain in women and men may differ, but to date gender differences in risk factors for post-MVC MSNP have not been assessed. In this prospective observational study, we evaluated for gender differences in risk factors for MSNP six weeks after MVC. European American men and women ≥18 and ≤ 65 years of age presenting to one of eight emergency departments (EDs) in four no-fault insurance states within 24 hours of MVC who did not have fracture or other injury requiring hospital admission were enrolled. Baseline ED assessment included an evaluation of participant demographic, pre-MVC health, and initial symptom characteristics. Six week telephone follow-up assessment included evaluation for the presence of MSNP (defined as neck pain ≥4 on 0 - 10 NRS during the past week). Participants reporting involvement in litigation at six week follow-up were excluded. Interactions between gender and other predictors were evaluated and relative risks (RRs) by gender were estimated using Poisson regression adjusted for study site. Interactions with p < .10 were considered significant. 711/948 (75%) of enrolled patients completed 6 week follow-up and were non-litigants. The strength of association (RR) between a number of predictors and MSNP significantly differed between women and men, including severe pre-MVC depression (1.2 vs. 2.8), high catastrophizing (1.2 vs. 3.5), highest age tertile (1.3 vs. 3.3), rear end collision (1.1 vs. 2.3), and increased estimated time to physical recover at time of initial ED visit (1.5 vs. 3.0). These findings indicate that risk factors for MSNP 6 weeks after MVC differ between women and men. Further studies are needed to better understand gender differences in the etiology of post-traumatic pain. Supported by NIAMS R01AR056328.

Worse pain outcomes are observed among individuals seeking monetary compensation after motor vehicle collision (MVC), but whether the etiology of persistent pain among such litigants differs from non-litigants remains poorly understood. One commonly used method for gaining insights into etiology is to evaluate risk factors for disease development. In this prospective observational study, we compared predictors of persistent pain after MVC among litigants and non-litigants. European Americans ≥18 years of age presenting to the emergency department (ED) within 24 hours of MVC who did not have a fracture or injury requiring hospital admission were enrolled. Baseline ED assessment included an evaluation of participant sociodemographic characteristics, pre-MVC health characteristics, MVC history, and participant cognitions and symptoms in the ED. Six week telephone follow-up evaluation assessed litigation status and neck pain intensity during the past week (0-10 NRS), scores ≥4 were defined as moderate/severe neck pain (MSNP). Candidate predictors of six week MSNP were assessed via logistic regression; significance levels were determined using Bonferroni correction (p=0.00125). Six week follow up was obtained in 849/948 (90%) of enrolled participants, and 148/849 (17%) reported that they had hired a lawyer to sue for compensation ("litigants"). MSNP was reported by 95/148 (64%) of litigants and 199/711 (28%) of non-litigants six weeks after MVC. Female sex, increased ED pain severity, and increased ED somatic symptom burden predicted 6 week MSNP among both litigants and non-litigants. Among litigants, unique predictors of 6 week MSNP included not working full time, not having health insurance, and being a vehicle passenger vs. driver. Among non-litigants, unique predictors of 6 week MSNP included believing that the MVC was someone else's fault and increased participant estimate of time to recovery (assessed at ED evaluation). These findings suggest that the etiology of persistent pain in litigants and non-litigants may differ. Supported NIAMS R01AR056328. Worse pain outcomes are observed among individuals seeking monetary compensation after motor vehicle collision (MVC), but whether the etiology of persistent pain among such litigants differs from non-litigants remains poorly understood. One commonly used method for gaining insights into etiology is to evaluate risk factors for disease development. In this prospective observational study, we compared predictors of persistent pain after MVC among litigants and non-litigants. European Americans ≥18 years of age presenting to the emergency department (ED) within 24 hours of MVC who did not have a fracture or injury requiring hospital admission were enrolled. Baseline ED assessment included an evaluation of participant sociodemographic characteristics, pre-MVC health characteristics, MVC history, and participant cognitions and symptoms in the ED. Six week telephone follow-up evaluation assessed litigation status and neck pain intensity during the past week (0-10 NRS), scores ≥4 were defined as moderate/severe neck pain (MSNP). Candidate predictors of six week MSNP were assessed via logistic regression; significance levels were determined using Bonferroni correction (p=0.00125). Six week follow up was obtained in 849/948 (90%) of enrolled participants, and 148/849 (17%) reported that they had hired a lawyer to sue for compensation ("litigants"). MSNP was reported by 95/148 (64%) of litigants and 199/711 (28%) of non-litigants six weeks after MVC. Female sex, increased ED pain severity, and increased ED somatic symptom burden predicted 6 week MSNP among both litigants and non-litigants. Among litigants, unique predictors of 6 week MSNP included not working full time, not having health insurance, and being a vehicle passenger vs. driver. Among non-litigants, unique predictors of 6 week MSNP included believing that the MVC was someone else's fault and increased participant estimate of time to recovery (assessed at ED evaluation). These findings suggest that the etiology of persistent pain in litigants and non-litigants may differ. Supported NIAMS R01AR056328.