Clinical and biological factors distinguishing subjects with and without pain

Objectives: To identify clinical and biological mediators that may distinguish subgroups of temporomandibular disorders (TMD) subjects and controls without TMD using cluster analyses. Methods: Three subject types were recruited: TMD subjects with TMD pain and disc displacement (n=23), pain-free TMD subjects with DD (n=15), and pain-free controls without TMD (n=13). Plasma, muscle biopsies, and TMJ synovial fluid were collected to measure F2-isoprostane (F2I), and substance P (SP). Ward's minimum variance cluster analysis (SAS software) was performed including depression and anxiety (SCL-90R), present pain intensity (0-10 NRS), characteristic pain (Global Chronic Pain Scale), and sensory-affective characteristic of pain (McGill Pain Questionnaire). Chi-square and ANOVA were used to evaluate differences across clusters on variables that did not take part in the generation of clusters to validate the cluster solution: RDC/TMD diagnoses, pressure pain threshold (PPT) and mediators. Results: External validation of the cluster solution supports 3 group profiles: Cluster 1, pain-free TMD and control subjects (n=25), Cluster 2 subgroup of 80% TMD subjects with pain (n=15), and Cluster 3 subgroup of 100% TMD subjects with pain (n=8). Specifically, PPT was significantly lower in cluster 3 when compared to clusters 1 and 2 (P <0.01). Pain characteristics were significantly more severe in cluster 3 when compared to cluster 2 (P < 0.05). There were no significant differences on level of psychological variables among all clusters (P>0.05). SP in plasma was significantly lower in cluster 2 and F2I in muscle was significantly lower in cluster 3, when compared to other clusters (P<0.05). Conclusion: SP and F2I may differentiate sub-groups of painful TMD with central sensitization being more prominent in cluster 3 based on elevated pain characteristics and the lower PPT compared to cluster 2. These results suggest different pathophysiological mechanisms may be present in painful TMD sub-groups (Supported by NIH/NIDCR U01 DE013331-01).