Comorbidity and familial aggregation of back/neck pain in the NIMH Family Study of Affective Spectrum Disorders.

OBJECTIVE: Back pain is associated with substantial Global Burden of Disease and is highly comorbid with mood and anxiety symptoms and syndromes. However, mechanisms underlying this association have not been well-elucidated. Here we apply data from the NIMH Family Study of Affective Spectrum Disorders to investigate the comorbidity, familial aggregation, and cross-aggregation of back/neck pain with mood disorder subtypes. METHODS: The sample includes 519 probands and 560 interviewed first-degree relatives. Lifetime DSM-IV Bipolar I, Bipolar II, and Major Depressive Disorder [MDD] were derived from semi-structured diagnostic interviews. Lifetime history of back or neck pain and its age of onset were self-reported retrospectively. Familial aggregation and cross-aggregation were estimated via mixed effects models in probands and interviewed first-degree relatives, while heritability and co-heritability (endophenotypic ranking value [ERV]) were estimated using full pedigrees. RESULTS: Over 45% of participants endorsed a history of back/neck pain. Back/neck pain was familial (adjusted odds ratio [aOR] 1.5, p = 0.04; h2 = 0.24, p = 0.009). Back/neck pain in probands was associated with MDD in relatives (aOR 1.5, p = 0.04; ERV = 0.17, p = 0.024), but not with bipolar disorder. Onset of back/neck pain occurred earlier in those with bipolar disorder compared to controls. CONCLUSION: Findings suggest common familial risk factors underlying back/neck pain with MDD, whereas there was within-individual comorbidity of bipolar with back/neck pain. Future studies that identify common factors that lead to either back/neck pain or MDD can inform prevention and interventions.

Nature and nurture. Genetic and environmental factors on the relationship between back pain and sleep quality.

BACKGROUND: Chronic low back pain (LBP), neck pain (NP), and sleep quality (SQ) are genetically influenced. All three conditions frequently co-occur and shared genetic aetiology on a pairwise base has been reported. However, to our knowledge, no study has yet investigated if these three conditions are influenced by the same genetic and environmental factors and the extent and pattern of genetic overlap between them, hence the current research. METHODS: The sample included 2134 participants. Lifetime prevalence of NP and LBP were assessed through a dichotomous self-reported question derived from the Spanish National Health Survey. SQ was measured using the Pittsburgh Sleep Quality Index Questionnaire. A common pathway model with sleep quality and back pain as latent factors was fitted. RESULTS: Our results highlight that a latent back pain factor, including both NP and LBP, is explained by both genetic (41%) and environmental (59%) factors. There are also significant unique environmental factors for NP (33%) and LBP (37%) respectively. Yet, specific genetic factors were scant (9%) for NP and negligible for LBP (0%). Genetic and environmental factors affecting SQ only contribute with 3% and 5% of the variance, respectively, to the common latent back pain variable. CONCLUSIONS: NP and LBP share most of their genetic variance, while environmental effects show greater specificity for each of the back pain locations. Associations with SQ were of a limited magnitude. SIGNIFICANCE: Our results confirm a significant association between both chronic NP and LBP and sleep quality. Such relationship comprises both genetic and environmental factors, with a greater relative weight of the latter. A large part of the individual variance for chronic LBP and chronic NP can be accounted for by a latent common factor of 'back pain'. Genetic influences for LBP and NP were mainly shared. However, environmental influences were common for both problems and specific for each of them in similar magnitudes.

microRNA let-7i-5p mediates the relationship between muscle fat infiltration and neck pain disability following motor vehicle collision: a preliminary study.

Persistent neck-pain disability (PNPD) is common following traumatic stress exposures such as motor vehicle collision (MVC). Substantial literature indicates that fat infiltration into neck muscle (MFI) is associated with post-MVC PNPD. However, little is known about the molecular mediators underlying this association. In the current study, we assessed whether microRNA expression signatures predict PNPD and whether microRNA mediate the relationship between neck MFI and PNPD. A nested cohort of 43 individuals from a longitudinal study of MVC survivors, who provided blood (PAXgene RNA) and underwent magnetic resonance imaging (MRI), were included in the current study. Peritraumatic microRNA expression levels were quantified via small RNA sequencing, neck MFI via MRI, and PNPD via the Neck Disability Index two-weeks, three-months, and twelve-months following MVC. Repeated measures regression models were used to assess the relationship between microRNA and PNPD and to perform mediation analyses. Seventeen microRNA predicted PNPD following MVC. One microRNA, let-7i-5p, mediated the relationship between neck MFI and PNPD. Peritraumatic blood-based microRNA expression levels predict PNPD following MVC and let-7i-5p might contribute to the underlying effects of neck MFI on persistent disability. In conclusion, additional studies are needed to validate this finding.

First Report of Pharmacogenomic Profiling in an Outpatient Spine Setting: Preliminary Results from a Pilot Study.

OBJECTIVE: Pharmacogenomics may help personalize medicine and improve therapeutic selection. This is the first study investigating how pharmacogenomic testing may inform analgesic selection in patients with spine disease. We profile pharmacogenetic differences in pain medication-metabolizing enzymes across patients presenting at an outpatient spine clinic and provide preliminary evidence that genetic polymorphisms may help explain interpatient differences in preoperative pain refractory to conservative management. METHODS: Adults presenting to our outpatient spine clinic with chief symptoms of neck and/or back pain were prospectively enrolled over 9 months. Patients completed the Wong-Baker FACES and numeric pain rating scales for their chief pain symptom and provided detailed medication histories and cheek swab samples for genomic analysis. RESULTS: Thirty adults were included (mean age, 60.6 ± 15.3 years). The chief concern was neck pain in 23%, back pain in 67%, and combined neck/back pain in 10%. At enrollment, patient analgesic regimens comprised 3 ± 1 unique medications, including 1 ± 1 opioids. After genomic analysis, 14/30 patients (47%) were identified as suboptimal metabolizers of ≥1 medications in their analgesic regimen. Of these patients, 93% were suboptimal metabolizers of their prescribed opioid analgesic. Nonetheless, pain scores were similar between optimal and suboptimal metabolizer groups. CONCLUSIONS: This pilot study shows that a large proportion of the spine outpatient population may use pain medications for which they are suboptimal metabolizers. Further studies should assess whether these pharmacogenomic differences indicate differences in odds of receiving therapeutic benefit from surgery or if they can be used to generate more effective postoperative analgesic regimens.

Leadership Style, Headache, and Neck Pain: The Moderating Role of the Catechol-O-Methyltransferase (COMT) Genotype.

OBJECTIVE: Leadership styles can influence subordinates' health. We investigated how the gene encoding the Catechol-O-Methyltransferase (COMT) enzyme (ie, COMT rs4680 Val158Met) influenced effects of abusive supervision and transformational leadership on subordinates' headache and neck pain. METHODS: Multiple group structural equation modeling (SEM) was employed to test associations of leadership with subordinates' pain 6 months after in a representative sample of the Norwegian working population (n = 996). Genotyping was performed by TaqMan technology. RESULTS: Abusive supervision was associated with increased risk, and transformational leadership with decreased risk, of headache and neck pain. Both leadership styles exhibited more pronounced effects in individuals with the Met/Met genotype. CONCLUSION: Met/Met employees were relatively vulnerable to adversity, but also relatively responsive to constructive leadership. Many workers may benefit more from constructive leadership than population-averaged associations might suggest.

Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions.

Chronic musculoskeletal pain affects all aspects of human life. However, mechanisms of its genetic control remain poorly understood. Genetic studies of pain are complicated by the high complexity and heterogeneity of pain phenotypes. Here, we apply principal component analysis to reduce phenotype heterogeneity of chronic musculoskeletal pain at four locations: the back, neck/shoulder, hip, and knee. Using matrices of genetic covariances, we constructed four genetically independent phenotypes (GIPs) with the leading GIP (GIP1) explaining 78.4% of the genetic variance of the analyzed conditions, and GIP2-4 explain progressively less. We identified and replicated five GIP1-associated loci and one GIP2-associated locus and prioritized the most likely causal genes. For GIP1, we showed enrichment with multiple nervous system-related terms and genetic correlations with anthropometric, sociodemographic, psychiatric/personality traits and osteoarthritis. We suggest that GIP1 represents a biopsychological component of chronic musculoskeletal pain, related to physiological and psychological aspects and reflecting pain perception and processing.

A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank.

BACKGROUND: Common types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203 309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK. METHODS: A genome-wide association study was performed adjusting for age, sex, BMI and nine population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication. RESULTS: We identified three genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 × 10-11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 × 10-10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 × 10-8 for rs62053992. In the replication stage, among four significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). CONCLUSIONS: We have identified three loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain.

Sleep quality and chronic neck pain: a cotwin study.

STUDY OBJECTIVES: Sleep quality and chronic neck pain (NP) are associated. However, the genetic influences on this association have not been explored. This study investigated the genetic and environmental influences on the association between sleep quality and chronic NP. METHODS: The sample comprised 2,328 individual twins from the Murcia Twin Registry (Spain). A bidirectional cotwin logistic regression analysis was performed (sleep quality assessed as the exposure and chronic NP as the outcome and vice versa). Analysis included 2 sequential stages: total sample analysis and within-pair twin case-control analysis. RESULTS: Sleep quality was significantly associated with chronic NP in the total sample analysis (adjusted odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.06, 1.12; P < .001); in the cotwin case-control analysis, including both monozygotic and dizygotic twin pairs (adjusted OR: 1.10; 95% CI: 1.04, 1.17; P = .001); in dizygotic pairs (Adjusted OR: 1.11; 95% CI: 1.03, 1.19; P = .005); but not in monozygotic pairs (adjusted OR: 1.08; 95% CI: 0.98, 1.19; P = .118). Chronic NP was significantly associated with poor sleep quality in the total sample analysis (adjusted OR: 1.80; 95% CI: 1.43, 2.26; P < .001); in the cotwin case-control analysis, including both monozygotic and dizygotic twin pairs (Adjusted OR: 1.63; 95% CI: 1.07, 2.47; P = .023); in dizygotic pairs (Adjusted OR: 1.80; 95% CI: 1.05, 3.09; P = .031), but not in monozygotic pairs (adjusted OR: 1.67; 95% CI: 0.80, 3.48; P = .170). CONCLUSIONS: The association between sleep quality and chronic NP is partially confounded by genetic factors.

Vitamin D insufficiency increases risk of chronic pain among African Americans experiencing motor vehicle collision.

African Americans experience an increased burden of motor vehicle collision (MVC), post-MVC musculoskeletal pain, and vitamin D insufficiency. In this prospective multicenter study, we tested the hypothesis that African Americans (n = 133) presenting to the emergency department after MVC with low peritraumatic vitamin D levels would have worse chronic musculoskeletal pain outcomes compared to individuals with sufficient vitamin D. Vitamin D levels were assessed in the early aftermath of MVC through enzyme-linked immunosorbent assay, and pain severity was assessed using the 0 to 10 numeric rating scale at 6 weeks, 6 months, and 1 year. In repeated-measures analysis, African American MVC survivors with vitamin D insufficiency experienced more severe chronic pain (ß = 1.18, P = 0.031). In secondary analyses, we assessed for evidence that the effect of vitamin D on post-MVC pain outcomes is mediated, at least in part, by the influence of vitamin D on genetic variants in genes involved in immune system regulation (IL-10 and NLRP3). Genotyping was performed using a genome-wide microarray using collected DNA samples. Secondary analyses suggest that the effect of vitamin D on post-MVC pain outcomes may be influenced by genetic variation in IL-10 and NLRP3. Further studies are needed to assess the impact of vitamin D insufficiency on pain outcomes in African Americans experiencing MVC and other common trauma exposures, to assess factors affecting this relationship, and to assess the efficacy of administering vitamin D in the immediate aftermath of MVC to prevent chronic pain. Such low-cost, nonopioid interventions are urgently needed to address chronic pain development after MVC.

COMT genotype and non-recovery after a whiplash injury in a Northern European population.

BACKGROUND: The COMT (Catechol-O-Methyl Transferase) gene may influence a person's vulnerability to develop long-term pain and some COMT single nucleotide polymorphisms (SNPs) may associate with patterns of acute or chronic pain. Many patients with whiplash-associated disorders (WADs) suffer from long-term pain and other related symptoms, but it is less known if genetic factors play a role in the recovery process. The primary aim of this study was to evaluate whether self-reported non-recovery, including pain, was related to COMT genotype in patients with WAD. The secondary aim was to investigate whether or not background factors, including mental health, were related to genotype and non-recovery. METHODS: A total of 133 patients with neck pain after a whiplash trauma were included. Background factors were collected and blood samples were taken during the acute phase after the accident. DNA was isolated from blood and used to genotype the SNPs rs6269, rs4633, rs4818 and rs4680 in the COMT gene; additionally haplotypes were estimated and haplogenotypes inferred. The patients were followed up after 12 months and asked to rate their recovery including pain, mental health and quality of life. RESULTS: The overall reported non-recovery rate at 12 months was 44% with no significant differences in distribution of the COMT haplotypes. High levels of self-reported pain (OR 7.2) and anxiety (OR 4.4) after the accident were associated with non-recovery, but not related to the haplotypes. None of the other background factors were related to the haplotypes or non-recovery. CONCLUSION: No association between self-reported non-recovery or pain levels and COMT haplotypes in patients with acute whiplash injuries could be detected. Independent replications are necessary to discard the hypothesis that COMT haplotypes do not influence non-recovery or pain levels in patients with acute whiplash injuries. High levels of initial pain and anxiety were associated with non-recovery, thereby confirming previously published reports.

Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration.

STUDY DESIGN: In vivo study defining expression of the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical intervertebral discs after painful whole-body vibration (WBV). OBJECTIVE: The goal of this study is to determine if BDNF and NGF are expressed in cervical discs after painful WBV in a rat model. SUMMARY OF BACKGROUND DATA: WBV is a possible source of neck pain and has been implicated as increasing the risk for disc disorders. Typically, aneural regions of painful human lumbar discs exhibit hyperinnervation, suggesting nerve ingrowth as potentially contributing to disc degeneration and pain. BDNF and NGF are upregulated in painfully degenerate lumbar discs and hypothesized to contribute to this pathology. METHODS: Male Holtzman rats underwent 7 days of repeated WBV (15 Hz, 30 min/d) or sham exposures, followed by 7 days of rest. Cervical discs were collected for analysis of BDNF and NGF expression through RT-qPCR and Western blot analysis. Immunohistochemistry also evaluated their regional expression in the disc. RESULTS: Vibration significantly increases BDNF messenger ribonucleic acid (mRNA) levels (P=0.036), as well as total-NGF mRNA (P=0.035). Protein expression of both BDNF (P=0.006) and the 75-kDa NGF (P=0.045) increase by nearly 4- and 10-fold, respectively. Both BDNF mRNA (R=0.396; P=0.012) and protein (R=0.280; P=0.035) levels are significantly correlated with the degree of behavioral sensitivity (i.e., pain) at day 14. Total-NGF mRNA is also significantly correlated with the extent of behavioral sensitivity (R=0.276; P=0.044). Both neurotrophins are most increased in the inner annulus fibrosus and nucleus pulposus. CONCLUSION: The increases in BDNF and NGF in the cervical discs after painful vibration are observed in typically aneural regions of the disc, consistent with reports of its hyperinnervation. Yet, the induction of nerve ingrowth into the disc was not explicitly investigated. Neurotrophin expression also correlates with behavioral sensitivity, suggesting a role for both neurotrophins in the development of disc pain. LEVEL OF EVIDENCE: N/A.

Modest associations between self-reported physical workload and neck trouble: a population-based twin control study.

OBJECTIVES: To investigate the relationship between self-reported physical workload and neck trouble (NT) in twins. Additionally, to explore whether the relationship between physical workload and NT is influenced by genetic factors. METHODS: A twin control study was performed within a population-based, cross-sectional questionnaire study using 3,208 monozygotic (MZ) and same-sexed dizygotic (DZ) twins aged 19-70. Twin pairs discordant for self-reported NT during the past year ("Any NT") were included. Self-reported physical workload in four categories was used as exposure ("sitting," "sitting and walking," "light physical," and "heavy physical" work). Paired analyses including conditional logistic regression were made for all participants and for each sex, and MZ and DZ pairs separately. RESULTS: No marked associations between physical workload and NT were seen. A moderate risk elevation in "heavy physical" work was seen in DZ men (odds ratio 2.3, 95% confidence intervals 1.3-4.0), but not in MZ men or the MZ or DZ women. CONCLUSIONS: The findings in some degree supported that "heavy physical" work is a determinant of NT, perhaps only in men, but hardly of any greater importance. The different results between DZ and MZ men suggest that genetic factors influence the relationship between physical workload and NT.

Genetic and environmental influences on non-specific neck pain in early adolescence: a classical twin study.

BACKGROUND: Prevalence of neck pain has increased among adolescents. The origins of adult chronic neck pain may lie in late childhood, but for early prevention, more information is needed about its aetiology. We investigated the relative roles of genetic and environmental factors in early adolescent neck pain with a classic twin study. METHODS: Frequency of neck pain was assessed with a validated pain questionnaire in a population-based sample of nearly 1800 pairs of 11-12-year-old Finnish twins. Twin pair similarity for neck pain was quantified by polychoric correlations, and variance components were estimated with biometric structural equation modelling. RESULTS: Prevalence of neck pain reported at least once monthly was 38% and at least once weekly 16%, with no significant differences between gender and zygosity. A greater polychoric correlation in liability to neck pain was found in monozygotic (0.67) than for dizygotic pairs (0.38), suggesting strong genetic influences. Model fitting indicated that 68% (95% confidence interval 62-74) of the variation in liability to neck pain could be attributed to genetic effects, with the remainder attributed to unshared environmental effects. No evidence for sex-specific genetic effects or for sex differences in the magnitude of genetic effects was found. CONCLUSIONS: Genetic and unique environmental factors seem to play the most important roles in liability to neck pain in early adolescence. Future research should be directed to identifying pathways for genetic influences on neck pain and in exploring effectiveness of interventions that target already identified environmental risk factors.

Genetic variation in the beta-2 adrenergic receptor is associated with chronic musculoskeletal complaints in adolescents.

BACKGROUND: There is significant evidence to suggest that psychological and stress-related factors are important predictors of the onset of chronic widespread pain (CWP) and fibromyalgia (FM). The hypothalamic-pituitary-adrenal axis, together with the efferent sympathetic/adrenomedullary system, influence all body organs (including muscles) during short- and long-term threatening stimuli. The aim of this study was to investigate the relationship between genetic variants in adrenergic candidate genes and chronic musculoskeletal complaints (MSCs) in adolescents. METHODS: Adolescents from the Western Australian Pregnancy (Raine) Cohort attending the 17-year cohort review completed a questionnaire containing a broad range of psychosocial factors and pain assessment (n = 1004). Blood samples were collected for DNA extraction and genotyping. Genotype data was obtained for 14 single nucleotide polymorphisms (SNPs) in two candidate genes - beta-2 adrenergic receptor (ADRB2) and catecholamine-O-methyltransferase (COMT). Haplotypes were reconstructed for all individuals with genotype data. RESULTS AND CONCLUSION: Both female gender and poor mental health were associated with (1) an increased risk for chronic, disabling comorbid neck and low back pain (CDCP); and (2) an increase in the number of areas of pain. Of the 14 SNPs evaluated, only SNP rs2053044 (ADRB2, recessive model) displayed an association with CDCP [odds ratio (OR) = 2.49; 95% confidence interval (CI) = 1.25, 4.98; p = 0.01] and pain in three to four pain areas in the last month (OR = 1.86; 95% CI = 1.13, 3.06; p = 0.02). These data suggest that genetic variants in ADRB2 may be involved in chronic MSCs.

[Effect of electroacupuncture at different acupoints on expression of cervico-spinal GDNF and BDNF and their receptor genes in neck-incision pain rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Futu" (LI 18), etc. on the expression of genes of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and their receptors in the cervico-spinal cord in neck-incision pain rats, so as to study its mechanism underlying incision-pain relief. METHODS: A total of 50 Sprague Dawley male rats were randomly divided into normal, model (incision pain), EA-Futu (LI 18), EA- Hegu (LI 4) - Neiguan (PC 6, LI 4-PC 6) and EA-Zusanli (ST 36)-Yanglingquan (GB 34, ST 36-GB 34) groups (n = 10/group). A 1.5 cm long longitudinal incision was made along the midline of the neck under anesthesia to duplicate neck-incision pain model. Thermal pain threshold (PT) was measured before and after modeling and after the treatment, respectively. EA (1-2 mA, 2 Hz/100 Hz) was applied to bilateral LI 18, PC 6-LI 4 and ST 36-GB 34 for 30 min. The expression of genes of GDNF and its receptor GFRalpha-1, and BDNF and its receptors TrkA, TrkB in the spinal cord (C1 - C4) tissue was detected by quantitative real-time-PCR. RESULTS: In comparison with pre-modeling in the same one group, the thermal PT levels were decreased obviously in the model, LI 18, LI 4-PC 6 and ST 36-GB 34 groups after neck incision (P < 0.05). Compared with the model group, the PT levels were increased markedly in LI 18, LI 4-PC 6 and ST 36-GB 34 groups after the EA treatment (P < 0.05). Correspondingly, the expression levels of spinal GDNF mRNA and GFRalpha-1 mRNA were obviously lower, as well as BDNF mRNA was markedly higher in the model group than in the control group (P < 0.05), and those of TrkA mRNA and TrkB mRNA were increased slightly in the model group than in the control group (P > 0.05). In comparison with the model group, the expression levels of spinal GDNF mRNA and GFRalpha-1 mRNA were up-regulated considerably (P < 0.001), whereas those of BDNF mRNA, TrkA mRNA and TrkB mRNA were decreased slightly (P > 0.05) in the LI 18, LI 4-PC 6 and ST 36-GB 34 groups after EA treatment. CONCLUSION: EA stimulation can significantly suppress pain reaction of neck incision, which is closely associated with its effects in up-regulating the expression of GDNF and its receptor GFRalpha-1 genes in the cervical spinal cord (C1 - C4).

Neck and back pain and intervertebral disc degeneration: role of occupational factors.

Back pain is a near-universal human experience at some time during life, and neck pain is also common. The overwhelming majority of low back and cervical pain is considered to be due to unspecified mechanical factors or disc degeneration, which is a common with ageing and, hence, in people of working age. Back pain and disc disease appear to have significant heritability, based upon twin studies, but environmental factors also contribute - including physical occupational activities in some studies - although the strength of this association remains uncertain. This article examines the contribution of genetic and environmental factors to back pain and disc disease, with a specific focus on occupational exposures.

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.

High heritability for concurrent low back and neck-shoulder pain: a study of twins.

STUDY DESIGN: A cross-sectional study on 21,225 twins based on a Web-based questionnaire was performed in 2005-2006 and administered by the Swedish Twin Registry. OBJECTIVE: To investigate the importance of genetic factors for the occurrence of "Concurrent low back (LBP) and neck-shoulder pain (NSP)" as well as of "Solely LBP," and "Solely NSP" in an adult population of women and men. SUMMARY OF BACKGROUND DATA: Many individuals suffering from LBP also have concurrent NSP, and little is known about the factors influencing the occurrence of this spinal comorbidity. METHODS: Heritability of Concurrent LBP and NSP, solely LBP, and solely NSP was analyzed in 2934 monozygotic twin pairs, 2009 same-sex dizygotic (DZ) twin pairs, and 1960 opposite-sex DZ twin pairs without any known rheumatic disorders using structural equation modeling (SEM). RESULTS: The SEM showed that 60% of the total variance for concurrent LBP and NSP can be explained by additive genetic effects, which was twice as large as for solely LBP (30%) and more than twice as large as for solely NSP (24%). CONCLUSION: Genetic factors had a considerably greater importance for the occurrence of concurrent LBP and NSP compared with solely LBP or solely NSP. The influence of genetic factors was similar for solely LBP and solely NSP.

Analyzing multivariate survival data using composite likelihood and flexible parametric modeling of the hazard functions.

In this paper, we model multivariate time-to-event data by composite likelihood of pairwise frailty likelihoods and marginal hazards using natural cubic splines. Both right- and interval-censored data are considered. The suggested approach is applied on two types of family studies using the gamma- and stable frailty distribution: The first study is on adoption data where the association between survival in families of adopted children and their adoptive and biological parents is studied. The second study is a cross-sectional study of the occurrence of back and neck pain in twins, illustrating the methodology in the context of genetic epidemiology.