Jeffrey S. Jones

Catechol O-Methyltransferase Haplotype Predicts Immediate Musculoskeletal Neck Pain and Psychological Symptoms After Motor Vehicle Collision

UNLABELLED Genetic variations in the catechol-O-methyltransferase (COMT) gene have been associated with experimental pain and risk of chronic pain development, but no studies have examined genetic predictors of neck pain intensity and other patient characteristics after motor vehicle collision (MVC). We evaluated the association between COMT genotype and acute neck pain intensity and other patient characteristics in 89 Caucasian individuals presenting to the emergency department (ED) after MVC. In the ED in the hours after MVC, individuals with a COMT pain vulnerable genotype were more likely to report moderate-to-severe musculoskeletal neck pain (76 versus 41%, RR = 2.11 (1.33-3.37)), moderate or severe headache (61 versus 33%, RR = 3.15 (1.05-9.42)), and moderate or severe dizziness (26 versus 12%, RR = 1.97 (1.19-3.21)). Individuals with a pain vulnerable genotype also experienced more dissociative symptoms in the ED, and estimated a longer time to physical recovery (median 14 versus 7 days, P = .002) and emotional recovery (median 8.5 versus 7 days, P = .038). These findings suggest that genetic variations affecting stress response system function influence the somatic and psychological response to MVC, and provide the first evidence of genetic risk for clinical symptoms after MVC. PERSPECTIVE The association of COMT genotype with pain symptoms, psychological symptoms, and recovery beliefs exemplifies the pleiotropic effects of stress-related genes, which may provide the biological substrate for the biopsychosocial model of post-MVC pain. The identification of genes associated with post-MVC symptoms may also provide new insights into pathophysiology.

Incidence and predictors of neck and widespread pain after motor vehicle collision among US litigants and nonlitigants

Summary Most individuals with pain sequelae 6 weeks after motor vehicle collision are not engaged in litigation. Evidence supports bidirectional effects between litigation and post–motor vehicle collision musculoskeletal pain outcomes. ABSTRACT Debate continues regarding the influence of litigation on pain outcomes after motor vehicle collision (MVC). In this study we enrolled European Americans presenting to the emergency department (ED) in the hours after MVC (n = 948). Six weeks later, participants were interviewed regarding pain symptoms and asked about their participation in MVC‐related litigation. The incidence and predictors of neck pain and widespread pain 6 weeks after MVC were compared among those engaged in litigation (litigants) and those not engaged in litigation (nonlitigants). Among the 859 of 948 (91%) participants completing 6‐week follow‐up, 711 of 849 (83%) were nonlitigants. Compared to nonlitigants, litigants were less educated and had more severe neck pain and overall pain, and a greater extent of pain at the time of ED evaluation. Among individuals not engaged in litigation, persistent pain 6 weeks after MVC was common: 199 of 711 (28%) had moderate or severe neck pain, 92 of 711 (13%) had widespread pain, and 29 of 711 (4%) had fibromyalgia‐like symptoms. Incidence of all 3 outcomes was significantly higher among litigants. Initial pain severity in the ED predicted pain outcomes among both litigants and nonlitigants. Markers of socioeconomic disadvantage predicted worse pain outcomes in litigants but not nonlitigants, and individual pain and psychological symptoms were less predictive of pain outcomes among those engaged in litigation. These data demonstrate that persistent pain after MVC is common among those not engaged in litigation, and provide evidence for bidirectional influences between pain outcomes and litigation after MVC.

Polymorphisms in the glucocorticoid receptor co-chaperone FKBP5 predict persistent musculoskeletal pain after traumatic stress exposure.

&NA; An association is demonstrated between genetic polymorphisms in the gene coding for a key regulatory molecule in the hypothalamic‐pituitary‐adrenal axis and persistent pain after trauma. &NA; Individual vulnerability factors influencing the function of the hypothalamic‐pituitary‐adrenal axis may contribute to the risk of the development of persistent musculoskeletal pain after traumatic stress exposure. The objective of the study was to evaluate the association between polymorphisms in the gene encoding FK506 binding protein 51, FKBP5, a glucocorticoid receptor co‐chaperone, and musculoskeletal pain severity 6 weeks after 2 common trauma exposures. The study included data from 2 prospective emergency department‐based cohorts: a discovery cohort (n = 949) of European Americans experiencing motor vehicle collision and a replication cohort of adult European American women experiencing sexual assault (n = 53). DNA was collected from trauma survivors at the time of initial assessment. Overall pain and neck pain 6 weeks after trauma exposure were assessed using a 0–10 numeric rating scale. After adjustment for multiple comparisons, 6 FKBP5 polymorphisms showed significant association (minimum P < 0.0001) with both overall and neck pain in the discovery cohort. The association of rs3800373, rs9380526, rs9394314, rs2817032, and rs2817040 with neck pain and/or overall pain 6 weeks after trauma was replicated in the sexual assault cohort, showing the same direction of the effect in each case. The results of this study indicate that genetic variants in FKBP5 influence the severity of musculoskeletal pain symptoms experienced during the weeks after motor vehicle collision and sexual assault. These results suggest that glucocorticoid pathways influence the development of persistent posttraumatic pain, and that such pathways may be a target of pharmacologic interventions aimed at improving recovery after trauma.

Measuring personal exposure to airborne mutagens and nicotine in environmental tobacco smoke

The exposure of individuals to environmental tobacco smoke (ETS) is of increasing public health concern because epidemiological studies have associated passive smoking with increased risk of a variety of adverse health effects among non-smokers including lung cancer. As a way to measure individual exposure to the mutagenic compounds in the complex mixture of ETS, we used a sensitive Salmonella/microsome micro pre-incubation (microsuspension) assay to detect mutagenicity of particulate matter collected on filters from low volume (1.7 1/min flow rate) personal sampling pumps. Airborne nicotine was collected concurrently as a marker for ETS exposure. In pilot-field studies, individual exposure to ETS was measured in two separate indoor environments in which smokers were present: a gambling casino and a bingo parlor. Total suspended particulate matter (TSP) was collected on filters worn near the breathing zone of non-smoking individuals. Sampling times ranged from 40 min to 6 h. All extracts of filters had detectable levels of mutagenic activity (TA98, +S9) resulting in airborne mutagenic activity concentrations of 500-5000 rev/m3. The mutagenic activity of the filters from the casino and bingo parlors was significantly correlated with total particulate matter per filters (n = 12; Rho = 0.85, p less than 0.01) and with airborne nicotine per filter (n = 12; Rho = 0.95, p less than 0.01). The microsuspension assay was sufficiently sensitive to detect the mutagens associated with extracts of particulate matter from low volume samples (0.2-0.6 m3) in these indoor environments over a relatively short sampling time, and could be useful in studies of personal exposure to the mutagens in environmental tobacco smoke. Further, airborne nicotine concentrations were highly correlated with airborne mutagenicity and the mutagenic activity associated with ETS could therefore be estimated by the concentrations of nicotine.

Using emergency department-based inception cohorts to determine genetic characteristics associated with long term patient outcomes after motor vehicle collision: Methodology of the CRASH study

BackgroundPersistent musculoskeletal pain and psychological sequelae following minor motor vehicle collision (MVC) are common problems with a large economic cost. Prospective studies of pain following MVC have demonstrated that demographic characteristics, including female gender and low education level, and psychological characteristics, including high pre-collision anxiety, are independent predictors of persistent pain. These results have contributed to the psychological and social components of a biopsychosocial model of post-MVC pain pathogenesis, but the biological contributors to the model remain poorly defined. Recent experimental studies indicate that genetic variations in adrenergic system function influence the vulnerability to post-traumatic pain, but no studies have examined the contribution of genetic factors to existing predictive models of vulnerability to persistent pain.Methods/DesignThe Project CRASH study is a federally supported, multicenter, prospective study designed to determine whether variations in genes affecting synaptic catecholamine levels and alpha and beta adrenergic receptor function augment social and psychological factors in a predictive model of persistent musculoskeletal pain and posttraumatic stress disorder (PTSD) following minor MVC. The Project CRASH study will assess pain, pain interference and PTSD symptoms at 6 weeks, 6 months, and 1 year in approximately 1,000 patients enrolled from 8 Emergency Departments in four states with no-fault accident laws.DiscussionThe results from this study will provide insights into the pathophysiology of persistent pain and PTSD following MVC and may serve to improve the ability of clinicians and researchers to identify individuals at high risk for adverse outcomes following minor MVC.

More Educated Emergency Department Patients are Less Likely to Receive Opioids for Acute Pain

Summary Of patients presenting to an emergency department for evaluation after a motor vehicle collision, those with higher educational attainment are less likely to receive opioids. ABSTRACT Inadequate treatment of pain in United States emergency departments (EDs) is common, in part because of the limited and idiosyncratic use of opioids by emergency providers. This study sought to determine the relationship between patient socioeconomic characteristics and the likelihood that they would receive opioids during a pain‐related ED visit. We conducted a cross‐sectional analysis of ED data obtained as part of a multicenter study of outcomes after minor motor vehicle collision (MVC). Study patients were non‐Hispanic white patients between the ages of 18 and 65 years who were evaluated and discharged home from 1 of 8 EDs in 4 states. Socioeconomic characteristics include educational attainment and income. Of 690 enrolled patients, the majority had moderate or severe pain (80%). Patients with higher education attainment had lower levels of pain, pain catastrophizing, perceived life threat, and distress. More educated patients were also less likely to receive opioids during their ED visit. Opioids were given to 54% of patients who did not complete high school vs 10% of patients with post‐college education (χ2 test P < .001). Differences in the frequency of opioid administration between patients with the lowest educational attainment (39%, 95% confidence interval 22% to 60%) and highest educational attainment (13%, 95% confidence interval 7% to 23%) remained after adjustment for age, sex, income, and pain severity (P = .01). In this sample of post‐MVC ED patients, more educated patients were less likely to receive opioids. Further study is needed to assess the generalizability of these findings and to determine the reason for the difference.

Pain distribution and predictors of widespread pain in the immediate aftermath of motor vehicle collision.

Musculoskeletal pain is common after motor vehicle collision (MVC). The study objective was to evaluate distribution of pain and predictors of widespread musculoskeletal pain in the early aftermath (within 48 h) of collision.

No man is an island: living in a disadvantaged neighborhood influences chronic pain development after motor vehicle collision.

&NA; Pain recovery after trauma is influenced by neighborhood socioeconomic characteristics. These findings are independent of individual characteristics, and moderated by genetic variation in FKBP5. &NA; Living in a lower socioeconomic status neighborhood has been shown to alter stress system function and is associated with a number of adverse health outcomes, but its influence on musculoskeletal pain (MSP) outcomes after traumatic stress exposures such as motor vehicle collision (MVC) has not been assessed. We performed a multicenter, prospective study that enrolled 948 European‐American individuals within 24 hours of MVC who were discharged home after emergency department evaluation. Follow‐up evaluations were completed via telephone or Internet survey 6 weeks, 6 months, and 1 year after MVC on 91%, 89%, and 91% of participants, respectively. A robust aggregate measure of census tract neighborhood disadvantage was derived, and individual‐level characteristics assessed included socioeconomic and demographic characteristics, pain prior to MVC, litigation status, and opioid use. MSP was assessed in the emergency department; MSP and pain interference with daily activity were assessed at 6 weeks, 6 months, and 1 year. After adjustment for individual‐level factors, living in more disadvantaged neighborhoods was associated with increased MSP (P = 0.0009) and increased pain interference with daily function (P < 0.0001). The relationship between neighborhood disadvantage and MSP was moderated by a common single nucleotide polymorphism, rs2817038, 5′ of the gene encoding FKBP5, a functional regulator of glucocorticoid receptor sensitivity (interaction P‐value = 0.0015). These data support the hypothesis that low neighborhood socioeconomic status increases the likelihood of worse MSP outcomes after traumatic stress exposures such as MVC, and that this influence is mediated in part via its influence on stress system function.

Chronic widespread pain after motor vehicle collision typically occurs through immediate development and nonrecovery: results of an emergency department-based cohort study.

Abstract Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops through the evolution of pain from regional to widespread or through the early development of widespread pain with nonrecovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European–American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. Pain extent was assessed in the ED and 6 weeks, 6 months, and 1 year after MVC on 100%, 91%, 89%, and 91% of participants, respectively. Individuals who reported prior CWP at the time of ED evaluation (n = 53) were excluded. Trajectory modeling identified a 2-group solution as optimal, with the Bayes Factor value (138) indicating strong model selection. Linear solution plots supported a nonrecovery model. Although the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC, which does not remit.

Effect of pain location and duration on life function in the year after motor vehicle collision

Summary In this prospective study of 948 subjects, axial and widespread pain had the greatest influence on life interference during the year after motor vehicle collision. ABSTRACT Persistent musculoskeletal pain is common after motor vehicle collision (MVC) and often results in substantial disability. The objective of this study was to identify distributions of post‐MVC pain that most interfere with specific life functions and that have the greatest interference with aggregate life function. Study data were obtained from a prospective longitudinal multicenter emergency department–based cohort of 948 European Americans experiencing MVC. Overall pain (0–10 numeric rating scale [NRS]), pain in each of 20 body regions (0–10 NRS), and pain interference (Brief Pain Inventory, 0–10 NRS) were assessed 6 weeks, 6 months, and 1 year after MVC. After adjustment for overall pain intensity, an axial distribution of pain caused the greatest interference with most specific life functions (R2 = 0.15–0.28, association P values of <.001) and with overall function. Axial pain explained more than twice as much variance in pain interference as other pain distributions. However, not all patients with axial pain had neck pain. Moderate or severe low back pain was as common as neck pain at week 6 (prevalence 37% for each) and overlapped with neck pain in only 23% of patients. Further, pain across all body regions accounted for nearly twice as much of the variance in pain interference as neck pain alone (60% vs 34%). These findings suggest that studies of post‐MVC pain should not focus on neck pain alone.