A comprehensive review on biomarkers associated with painful temporomandibular disorders

Abstract

Pain of the orofacial region is the primary complaint for which patients seek treatment. Of all the orofacial pain conditions, one condition that possess a significant global health problem is temporomandibular disorder (TMD). Patients with TMD typically frequently complaints of pain as a symptom. TMD can occur due to complex interplay between peripheral and central sensitization, endogenous modulatory pathways, and cortical processing. For diagnosis of TMD pain a descriptive history, clinical assessment, and imaging is needed. However, due to the complex nature of pain an additional step is needed to render a definitive TMD diagnosis. In this review we explicate the role of different biomarkers involved in painful TMD. In painful TMD conditions, the role of biomarkers is still elusive. We believe that the identification of biomarkers associated with painful TMD may stimulate researchers and clinician to understand the mechanism underlying the pathogenesis of TMD and help them in developing newer methods for the diagnosis and management of TMD. Therefore, to understand the potential relationship of biomarkers, and painful TMD we categorize the biomarkers as molecular biomarkers, neuroimaging biomarkers and sensory biomarkers. In addition, we will briefly discuss pain genetics and the role of potential microRNA (miRNA) involved in TMD pain.

Preclinical models of deep craniofacial nociception and temporomandibular disorder pain

“…Biochemical studies demonstrate the changes in the level of inflammatory mediators, which can sensitize the nociceptors in the deep craniofacial tissues [ [22] , [23] , [24] , [25] ]. Proinflammatory mediators affect nociception in the deep craniofacial tissues.…”

“…Painful TMD with disk displacement (DD) without reduction displays higher levels of IL-1 beta, TNF-alpha and TNF-beta in the TMJ compared with that with DD with reduction [ 27 ]. TMD patients suffering from osteoarthritis show a higher level of IL-1 beta in synovial fluids [ 22 , 26 , 27 ]; however, most cytokines except IL-1 beta are less correlated with pain [ 26 ]. IL-1 beta has been reported to play critical roles on the development and progression of TMD pain [ 22 , 24 ].…”

“…TMD patients suffering from osteoarthritis show a higher level of IL-1 beta in synovial fluids [ 22 , 26 , 27 ]; however, most cytokines except IL-1 beta are less correlated with pain [ 26 ]. IL-1 beta has been reported to play critical roles on the development and progression of TMD pain [ 22 , 24 ]. IL-2, -8 and -13 in the blood serum also indicate significant effects on generalized pain in TMD patients [ 28 ].…”

“…Myofascial TMD pain patients display changes in the level of inflammatory mediators in the masseter muscle [ 22 ]. For example, the levels of cytokines including IL-6, 7, 8 and 13 are elevated in the masseter muscle; however, there is no direct cause-relation between pain and cytokine levels [ 30 ].…”

“…Neural changes in the CNS play critical roles on TMD pain [ 6 , 14 , 19 , 21 , [53] , [54] , [55] ]. Painful TMD displays less tissue injury in the deep craniofacial tissues, while the correlation of elevated inflammatory mediators with chronic pain is inconsistent [ [22] , [23] , [24] , 26 ]. TMD pain could be associated with comorbid negative psychology and disturbances in the body [ 14 , 16 , 18 ].…”