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The goals of this study were to determine if symptoms of posttraumatic stress disorder (PTSD) are related to the pain of temporomandibular disorders (TMD) in a community-based sample of female twin pairs, and if so, to ascertain if the association is due to the presence of chronic widespread pain (CWP) and familial/genetic factors.
Data were obtained from 630 monozygotic and 239 dizygotic female twin pairs participating in the University of Washington Twin Registry. PTSD symptoms were assessed with the Impact of Events Scale (IES), with scores partitioned into terciles. TMD pain was assessed with a question about persistent or recurrent pain in the jaw, temple, in front of the ear, or in the ear during the past 3 months. CWP was defined as pain located in 3 body regions during the past 3 months. Random effects regression models, adjusted for demographic features, depression, CWP, and familial/genetic factors, examined the relationship between the IES and TMD pain.
IES scores were significantly associated with TMD pain (P < 0.01). Twins in the highest IES tercile were almost 3 times more likely than those in the lowest tercile to report TMD pain, even after controlling for demographic factors, depression, and CWP. After adjusting for familial and genetic factors, the association of IES scores with TMD pain remained significant in dizygotic twins (Ptrend = 0.03) but was not significant in monozygotic twins (Ptrend = 0.30).
PTSD symptoms are strongly linked to TMD pain. This association could be partially explained by genetic vulnerability to both conditions but is not related to the presence of CWP. Future research is needed to understand the temporal association of PTSD and TMD pain and the physiological underpinnings of this relationship.
Temporomandibular Disorders (TMDs) are a group of conditions characterized by signs and symptoms of the muscles of mastication, temporomandibular joint, and related structures. Chronic pain is the most common symptom of TMDs and the primary reason for seeking treatment. TMDs are the most frequent diagnoses among patients with chronic orofacial pain problems.1 The estimated prevalence of painful TMDs is 10 – 12% with a predominance of young women.2–4 TMDs also share common characteristics with other types of chronic pain including pain features and behavioral and psychosocial dysfunction.5 Further, the chronic regional pain associated with TMDs may become generalized and extend beyond the facial region.6–8 In these cases, patients may experience chronic widespread pain (CWP) and fibromyalgia, a common form of non-articular rheumatism characterized by diffuse musculoskeletal pain and tender points on examination.9
Depression, somatization, and pain-related catastrophizing strongly influence the symptoms and functioning of TMD patients.10–12 Several clinic-based studies, but no community-based studies, have documented that TMDs are also associated with the symptoms of posttraumatic stress disorder (PTSD)13–15 and with the clinically diagnosed disorder.15, 16 PTSD appears to be the second most common psychiatric diagnosis among chronic orofacial pain patients after depression.16 Likewise, the association between PTSD and CWP and fibromyalgia is well documented in clinical as well as community samples.17–22 Previous studies, however, did not address whether the association of PTSD with TMD could be partially explained by the co-existence of TMDs with CWP and fibromyalgia.13–15
This study examines the association of PTSD and TMD pain among female twins enrolled in a community-based twin registry in Washington State. In these analyses, we address the following questions: 1) Are the symptoms of PTSD and TMD pain associated? 2) Does CWP account for the association between PTSD and TMD pain? and 3) Do familial/genetic factors account for the association of PTSD symptoms and TMD pain?
The University of Washington Twin Registry is a community-based sample of twins derived from the drivers' license applications of the Washington State Department of Licensing. In Washington State drivers' license numbers are derived from a person's name and date of birth, thus, the Department of Licensing asks every new applicant if s/he is a twin to avoid issuing duplicate license and identification numbers to twins. Because state agencies in Washington are permitted by law to share data, the Department of Licensing has provided a list of all new drivers' license applicants who are twins to the University of Washington since 1998. Upon receiving the names from the Department of Licensing, the University of Washington Twin Registry staff sends each twin an invitation to join, a brief survey to complete, and an incentive. If the twin does not respond within one month, a second invitation and survey are mailed. The co-twin is mailed a survey using contact information provided by the index twin. The University of Washington Human Subjects Review Committee approved the procedures for establishing the twin registry and all data collection involved in this study. Informed consent was obtained from all participants. Because TMDs and CWP disproportionately affect women, our analyses were limited to female twins.
The brief survey contains items on demographics, symptoms, physician-diagnosed health conditions such as depression, PTSD, and TMDs, habits, health care use, and various abridged, standardized measures of physical and mental health.
As part of the mailed questionnaire all twins were asked questions about childhood similarity to assess zygosity. Studies have shown that questions about childhood similarity in twin pairs can be used to correctly classify zygosity with an accuracy of 95 – 98% compared with zygosity determined by biological indicators.23, 24 Responses to these similarity questions were used in a multi-step process to assign zygosity, which identified 630 monozygotic (MZ) and 239 dizygotic (DZ) female twin pairs eligible for the current study.
Sociodemographic factors collected in the survey included age, gender, race, education, and marital status. One question inquired about a doctor diagnosis of depression. Questions about CWP were adapted from the self-report form of the London Fibromyalgia Epidemiology Study Screening Questionnaire.25 The CWP questions also were similar to those administered by mail and telephone in several European population-based studies conducted to ascertain the prevalence of chronic pain.26–30 Twins were asked about body pain in 3 regions: 1) shoulders, arms, or hands, 2) legs or feet, and 3) neck, chest, or back. For each region, information was obtained on whether the pain lasted at least one week during the past 3 months. CWP was defined as pain experienced in all 3 regions.
PTSD occurs when an overwhelming traumatic event results in intense fear, helplessness, horror, intrusive thoughts, and avoidance of stimuli associated with the trauma.31 PTSD symptoms were identified by using the Impact of Events Scale (IES), which assesses current distress resulting from a stressful life event.32 The IES captures qualities of conscious experiences that encompass stressful life events, such as bereavement or personal injuries from accidents, violence, illness, or surgery.32 In previous studies, the IES was strongly correlated with a diagnosis of PTSD,33 even though the IES measures only the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) intrusion and avoidance symptom criteria for PTSD.31 As a screening measure for PTSD, the sensitivity of the IES ranges from 0.94 – 1.00 and the specificity ranges from 0.78 – 0.84.34
We used 11 of the 15 original IES items, deleting the 4 original items that correlated most poorly with the IES intrusion and avoidance subscales in the cluster analysis conducted by the developers of the IES.32 Internal reliability of the IES was assessed by using Cronbach's alpha and validity was evaluated by its concordance with a self-report of PTSD diagnosed by a physician. For the 11 IES items used in this analysis, the Cronbach's alpha was 0.90, indicating a high degree of internal consistency. Likewise, the validity of the IES was demonstrated by a significant trend based on a simple logistic regression between the terciles of the IES score and a doctor diagnosis of PTSD (β = 0.06, P < 0.0001).
Each IES item has 4 response categories and values are summed to create an overall score (range 0 – 55). We grouped the scores into terciles representing increasing levels of current distress: 0 – 10 (lowest distress), 11 – 27 (moderate distress), and 28 and above (highest distress). We only included twins who answered at least 6 of the 11 IES items. Missing values were imputed by using the respondent's average score across completed items using published methods.35
The survey included a question derived from the Life Pain Questionnaire, which was developed by researchers to screen for common chronic pain conditions such as TMD and headaches.2 Twins were asked about TMD pain as follows: “In the past 3 months, have you had persistent or recurrent pain in the face, jaw, temple, in front of the ear, or in the ear?” This question has been validated and successfully used by other investigators to screen for TMDs. The calculated sensitivity for a diagnosis of TMD ranges from 89 – 100% and specificity from 37 – 69%.36, 37 In the twin sample, there was a modest association between the TMD pain question and a self-reported doctor diagnosis of TMD (κ = 0.22).
Initial descriptive analyses examined the distribution of sociodemographic factors, depression, CWP, and IES scores according to TMD pain status. The difference across TMD pain status of these variables was statistically examined by a Chi-square test for proportions or a t-test for means. To investigate the association of the IES with TMD pain, a random-effects model was fitted to the twin data, which accounts for the lack of independence of twins within a pair.38 We initially modeled the association between the IES and TMD pain to estimate the overall effect in all female twin pairs, and then separately for MZ and DZ pairs.39 In the analysis, we created indicator variables for each tercile of the IES, with the lowest tercile serving as the reference level, to obtain odds ratios and 95% confidence intervals. To statistically test for trend, we conducted an analysis using the ordinal IES scores. A second set of analyses included age, marital status, education, race, depression, and CWP as covariates in the regression models to adjust for their potentially confounding effects.
In our subsequent modeling, we specified within-pair effects separately for MZ and DZ pairs. The DZ within-pair odds ratios were adjusted for familial and some genetic influences; DZ twins share a similar family environment but, on average, only 50% of their genes. Because MZ twins share identical genes, the within-pair effect is an estimate adjusted for both familial and genetic factors. If adjusting for factors twins share such as familial environment and genetics eliminates the within-pair association between IES and TMD pain, then shared factors contribute to the IES-TMD pain association. Alternately, if the adjusted within-pair effects are attenuated but still significant, it suggests the IES-TMD pain association is partly explained by shared familial factors in DZ twins and familial and genetics factors in MZ twins. Lastly, greater within-pair effects for DZ than MZ twins suggest shared genetic influence on both IES scores and TMD pain. The resulting odds ratios were adjusted for age, marital status, education, race, depression, and CWP. We used Stata/SE software, Version 9.0 for all statistical analyses.40
Table 1 presents the demographic and clinical characteristics of the twins by their TMD pain status. More than 70% of twins were MZ. Among all twins, the mean age was 33 years, 85% were white, 34% were married, and the average length of schooling was 14 years. Twins with TMD pain were younger (P = 0.04), had fewer years of education (P = 0.01), were more likely to report depression and CWP, and had higher IES scores (P's < 0.01) than twins without TMD pain.
Of 1,738 twins, 252 (14.5%) reported experiencing TMD pain in the preceding 3 months. Figure 1 shows the prevalence rates of TMD pain by IES severity. The prevalence of TMD pain increased with increasing IES terciles, from 8% and 7% in the lowest terciles to 23% and 26% in the highest terciles for MZ and DZ, respectively.
Table 2 presents the unadjusted and adjusted odds ratios and 95% confidence intervals for the association of the IES with TMD pain in all twins and separately for MZ and DZ pairs. Even after adjusting for sociodemographic factors, self-reported depression, and CWP, the IES score and TMD pain were associated in all twins (Ptrend < 0.01). Compared to those in the lowest IES tercile, twins in the highest tercile were 2.8 times more likely to report TMD pain. A similar pattern was observed in both MZ and DZ twin pairs.
Table 3 displays the unadjusted and adjusted within-pair associations of the IES and TMD pain separately in MZ and DZ pairs. After adjusting for sociodemographic factors, depression, CWP, and familial and genetic influences, within-pair trends were still not significant in MZ twins (Ptrend = 0.30) but remained significant in DZ pairs (Ptrend = 0.03). Odds ratios at the highest tercile were 1.4 and 2.7 in MZ and DZ pairs, respectively. Although the within-pair effect was much larger in DZ than MZ twins, the difference was not significant (P = 0.13).
We found that symptoms of PTSD, as measured by the IES, were strongly related to the presence of TMD pain. Further, the increased prevalence of TMD pain across terciles of increasing IES scores was strong and significant even after adjusting for demographic factors, depression, and CWP. Because these findings from a community-based sample were consistent with those from clinically ascertained samples,14, 15 the relationship between PTSD symptoms and TMD pain does not appear to be an artifact of clinical ascertainment. Additionally, this association was not affected by the co-occurrence of CWP with TMD pain.
This is the first study of PTSD symptoms and TMD pain in a twin population. We examined whether the relationship between PTSD symptoms and TMD pain was due to shared familial/genetic factors. We found that the association between PTSD symptoms and TMD pain did not exist in MZ twin pairs and was attenuated in DZ twin pairs after controlling for shared familial and genetic factors. Although non-significant, the within-pair effect was diminished in MZ pairs compared with DZ pairs, suggesting that confounding due to genetic influences may partially explain the strong association between PTSD symptoms and TMD. These results are interesting in light of the sparse literature on the familial/genetic contributions to TMDs. For example, the only twin study of temporomandibular joint disorder found individualized environmental factors were the major determinants of variance.41 Further, a family study observed symptoms of myofascial TMDs and other musculoskeletal conditions were not greater in first degree relatives of probands with TMDs than controls.42 Twin studies of other pain conditions, however, have demonstrated familial/genetic influences. For example, one study found that low back and neck pain were highly heritable, with 52 – 68% of the variance for low back pain and 35 – 58% of the variance for neck pain attributable to genetic factors.43 Studies of fibromyalgia also have demonstrated a familial/genetic influence.44, 45 Lastly, we found a robust association between PTSD symptoms and CWP that cannot be explained by confounding due to familial/genetic influences.17
The mechanisms responsible for the association between chronic pain conditions such as TMDs and CWP and PTSD are unknown.46 Models of mutual maintenance and shared vulnerability have gained some acceptance in recent years.47, 48 Pre-existing abnormalities in hypothalamic pituitary adrenal and autonomic function could also predispose an individual to chronic pain conditions, PTSD, or both after a traumatic event.49 Brain imaging studies have found that psychological trauma and pain are processed in overlapping areas of the brain.50, 51 Understanding the underlying physiology of this overlap in the brain regions involved in the experience of trauma and pain could shed light on this intriguing association. Regardless of the underlying mechanism, however, our findings underscore the need to recognize the link between PTSD and TMDs, assess patients with either condition for comorbidity, and treat the symptoms of both disorders.
This study has several limitations. First, although the IES is used extensively as a measure of PTSD symptoms, we were unable to include the complete 15-question item version. However, the internal consistency and validity of the 11 questions that were retained were high. Second, the IES records PTSD symptoms that are not anchored to a specific traumatic experience, so the impact of a specific event is unclear. Thus, the IES may be measuring a “trait” rather than a “state”, that is, a stereotypical way of responding to traumatic events rather than a specific response to a single event. Third, our sample was predominately comprised of MZ twins. Finally, our measure of TMD pain was based on a single question, which had a modest association with self-reported doctor diagnosis of TMD. Findings from this study should be replicated using a comprehensive assessment of TMD pain.
In conclusion, in our large, unselected sample of twins, PTSD symptoms and TMD pain were strongly associated and not explained by co-existing CWP. This relationship could be partially explained by shared genetic vulnerability to both conditions. Previous studies of PTSD and TMDs typically have involved clinical samples with unknown selection biases and did not control for the presence of generalized pain conditions such as CWP. Future studies need to examine the viability of mutual maintenance and shared vulnerability models, as well as the central nervous system mechanisms that may play a role in the link between PTSD and pain.
This research was supported by National Institutes of Health awards 5 U19 AI38429-08 (Dr. Buchwald) and R55AR051524 (Dr. Afari). Dr. Afari is funded by National Institutes of Health award 7 R01 AR051524-02.
Portions of this research were presented at the First Annual NIH Pain Consortium Symposium, Bethesda, MD, April 2006.