Multisystem dysregulation in painful temporomandibular disorders

Abstract

Multiple physiological and psychological regulatory domains may contribute to the pathophysiology of pain in temporomandibular disorder (TMD) and other bodily pain conditions. The purpose of this study was to evaluate the relationship between multisystem dysregulation and the presence of TMD pain, as well as the presence of different numbers of comorbid pain conditions in TMD. Secondary data analysis was conducted in 131 non-TMD (without comorbid pain) controls, 14 TMD subjects without comorbid pain, 78 TMD subjects with 1 comorbid pain, and 67 TMD subjects with multiple comorbid pain conditions who participated in a TMD genetic study. Twenty markers from sensory, autonomic, inflammatory, and psychological domains were evaluated. The results revealed that 1) overall dysregulation in multiple system domains (OR [odds ratio] = 1.6, 95% confidence interval [CI] = 1.4-1.8), particularly in the sensory (OR = 1.9, 95% CI = 1.3-2.9) and the psychological (OR = 2.1, 95% CI = 2.1-2.7) domains, were associated with increased likelihood of being a painful TMD case; and 2) dysregulations in individual system domains were selectively associated with the increased odds of being a TMD case with different levels of comorbid persistent pain conditions. These outcomes indicate that heterogeneous multisystem dysregulations may exist in painful TMD subgroups, and multidimensional physiological and psychological assessments can provide important information regarding pathophysiology, diagnosis, and management of pain in TMD patients.

Perspective: The concurrent assessment of multiple physiological and psychological systems is critical to our understanding of the pathophysiological processes that contribute to painful TMD and associated comorbid conditions, which will ultimately guide and inform appropriate treatment strategies that address the multisystem dysregulation associated with complex and common persistent pain conditions.

Keywords: Temporomandibular disorders; comorbid pain conditions; headache; multisystem dysregulation.

Figure 1

Percentage of subjects within TMD subgroups with GCPS Grades II to IV at different pain locations. GCPS Grade I, low disability–low intensity; Grade II, low disability–high intensity; Grade III, high disability–moderately limiting; and Grade IV, high disability–severely limiting. GCPS Grades II to IV were selected to represent “clinical significant pain.” *P < .001 for the following: TMD + ≥2 pain vs TMD only; TMD + ≥2 pain vs TMD + 1 pain.

Figure 2

Likelihood of being TMD subgroup cases by total MDI score. The MDI total score is differently associated with the odds of being TMD subgroups based on the number of comorbid persistent pain conditions. Odds ratios were calculated for each case classification relative to controls from a multinomial logistic regression model adjusted for age (n = 230 females). *P = .002, **P < .001.

Figure 3

Likelihood of being TMD subgroup cases by sensory domain score. The MDI sensory domain score is differently associated with the odds of being TMD subgroups based on the number of comorbid persistent pain conditions. Odds ratios were calculated for each case classification relative to controls from a multinomial logistic regression model adjusted for age and dysregulation from autonomic, inflammatory, and psychological domains (n = 230 females). *P ≤.001.

Figure 4

Likelihood of being TMD subgroup cases by autonomic domain score. The MDI autonomic domain score is not associated with the odds of being TMD subgroups based on the number of comorbid persistent pain conditions. Odds ratios were calculated for each case classification relative to controls from a multinomial logistic regression model adjusted for age and dysregulation from sensory, inflammatory, and psychological domains (n = 230 females).

Figure 5

Likelihood of being TMD subgroup cases by inflammatory domain score. The MDI inflammatory domain score is not associated with the odds of TMD subgroups based on the number of comorbid persistent pain conditions. Odds ratios were calculated for each case classification relative to controls from a multinomial logistic regression model adjusted for age and dysregulation from sensory, autonomic, and psychological domains (n = 230 females).

Figure 6

Likelihood of being TMD subgroup cases by psychological domain score. The MDI psychological domain score is differently associated with the odds of TMD subgroups based on the number of comorbid persistent pain conditions. Odds ratios were calculated for each case classification relative to controls from a multinomial logistic regression model adjusted for age and dysregulation from sensory, autonomic and inflammatory domains (n = 230 females). *P < .001.