Animal Models of Temporomandibular Disorder

Abstract

Temporomandibular disorders (TMD) are a group of diseases in the oral and maxillofacial region that can manifest as acute or chronic persistent pain, affecting millions of people worldwide. Although hundreds of studies have explored mechanisms and treatments underlying TMD, multiple pathogenic factors and diverse clinical manifestations make it still poorly managed. Appropriate animal models are helpful to study the pathogenesis of TMD and explore effective treatment measures. At present, due to the high cost of obtaining large animals, rodents and rabbits are often used to prepare TMD animal models. Over the past decade, various animal models have been intensively developed to understand neurobiological and molecular mechanisms of TMD, and seek effective treatments. Although these models cannot carry out all clinical features, they are valuable in revealing the mechanisms of TMD and creating curative access. Currently, there are multitudinous animal models of TMD research. They can be constructed in different means and summarized into four ways according to the various causes and symptoms, including chemical induction (intra-articular injection of ovalbumin, collagenase, formalin, vascular endothelial growth factor, intramuscular injection of complete Freund's adjuvant, etc.), mechanical stress stimulation (passive mouth opening, change of chewing load), surgical operation (partial disc resection, joint disc perforation) and psychological stress induction. Here, we summarize and discuss different approaches of animal models for determining neurophysiological and mechanical mechanisms of TMD and assess their advantages and limitations, respectively.

Preclinical models of deep craniofacial nociception and temporomandibular disorder pain

“…Pain research to investigate its mechanism has shown significant progress with the establishments of preclinical models [ [14] , [15] , [16] , [17] , [96] , [97] , [98] ]. In particular, behavioral alterations of nociception have been key indicators for the investigation of the similarity between animals and human pain.…”

“…As TMD pain is multidimensional experiences, preclinical models need to possess such characters. It is, however, difficult to incorporate those into a single animal model [ [15] , [16] , [17] ]. Researchers have often picked one or two risk factors like local injury (e.g.…”

“…inflammation), psychological stress and different levels of hormones. Then, effects of the risk factor that we built in the animals artificially have been determined on nociception in the deep craniofacial tissues [ 6 , 14 , 15 , 17 , 90 , 96 ].…”

“…The other well-known local inflammatory model is the animals receiving formalin into the facial region [ 15 , 107 , 140 ]. The advantages of this model include that nociception in the deep craniofacial tissues could be quantified by the spontaneous behaviors in animals [ 107 ].…”

“…First, the neural mechanisms for TMD pain are discussed based on the clinical and preclinical studies. Emphasis is directed on the discussion of validity and characteristics of preclinical models for TMD [ [14] , [15] , [16] , [17] ]. Further, the experimental procedures to identify the nociceptive responses in the deep craniofacial tissues are discussed in the preclinical models.…”