Temporomandibular disorders (TMD) affect approximately 12% of the US population, predominately women in their childbearing years and of those affected by TMD, greater than 60% have masticatory muscle pain as their main complaint. Muscle pain has been shown to be associated with inflammation and muscle fiber injury generated after concentric or eccentric contractions in limb muscle and may similarly occur in jaw muscle after concentric or eccentric contractions during bruxism. Several studies have demonstrated that the masseter muscle has an impaired regenerative capacity; however, the cellular basis for this impaired capacity is unknown. Evidence exists for decreased satellite cell activation and proliferation in masseter in response to injury. However, it has yet to be established if this defect resides in satellite cell number, in their ability to effectively activate and proliferate in response to factors released in injury or in inflammatory response mechanisms. We provide preliminary evidence that the inflammatory response may be augmented and prolonged in masseter in response to freeze-injury and is manifested by increased numbers of mast cells. Mast cells have been demonstrated to be not only associated with a decrease in muscle viability after damage, but also may be responsible for pain associated with muscle inflammation. Thus one objective of this proposal is to examine events in masseter and in limb muscle repair in response to a freeze injury, to detect differences that might explain the impaired repair capacity of the masseter and to examine how mast cell response may contribute to this decreased regenerative potential. Standardized injury models that duplicate naturally occurring muscle damage in ? masseter during bruxism are essential to our understanding of the processes that contribute to muscle inflammation and pain in TMD. Therefore, we propose to also examine a more physiologically relevant model of muscle injury to determine if localized damage to the masseter elicited by eccentric and concentric contractions also generates an augmented inflammatory response and results in delayed repair.
Two specific aims are proposed.
Specific Aim 1 : Examine events in the inflammatory response to a freeze-induced injury in masseter and tibialis anterior.
This specific aim i s designed to test the hypothesis that the primary defect in masseter muscle repair resides in its inflammatory response to damage, manifested as increased numbers of mast cells and recurrent necrosis and resultant fibrotic repair;
Specific Aim 2 : Examine events in masseter muscle repair in response to damage from concentric and eccentric contraction. In this specific aim we propose to examine muscle fiber injury and repair in masseter after experimental stimulation to elicit concentric or eccentric contractions.
This specific aim will allow us to experimentally test the hypothesis that concentric or eccentric contractions such as those experienced during jaw clenching or bruxism result in muscle fiber damage in the masseter that prompts a prolonged inflammatory response and delay in repair. ? ? ?