Neuromuscular Post doctoral fellowship: Emory University, Atlanta, GA
Temporomandibular disorders (TMDs) are characterized by chronic muscle
tenderness and pain in the masticatory muscles and/or temporomandibular
joints. The disease disproportionately affects women. A variety of etiologic
factors have been suggested as the cause of this pain and dysfunction in
the temporomandibular system. Head or neck trauma is highly correlated with
the development of clinical symptoms of TMDs. Masticatory muscles have
different biochemical properties as compared to other skeletal muscles which
may increase the vulnerability to trauma, affect the reparative process
as well as the response to inflammatory mediators normally released during
tissue damage. One of the features of TMDs is the spread of pain from a
localized trauma to involve numerous masticatory structures. Activation
of nociceptive neurons during tissue damage leads to release of inflammatory
neuropeptides. Such activation and release may result in the release of
similar peptides from surrounding intramuscular neurons, leading to an amplification
of localized immune or inflammatory responses which occur during tissue
damage. The overall goals of this proposal are to 1) define the
response of the masseter muscle to localized trauma and 2) evaluate
the action of inflammatory peptides both on reparative processes within
the muscle and on stimulation of masticatory afferents. An overall theme
to these studies is that sex hormones differentially affect the response
of masseter muscle to injury or inflammatory peptides. Therefore, in all
cases we will examine gender based differences in specific tissue responses.
The specific hypotheses to be tested are 1) The normal regenerative
response to localized injury in the masseter muscles differs from that in
limb muscle 2) Focal injury to the masseter muscle stimulates production
of inflammatory peptides in masticatory afferent neurons 3) Perturbations
of the temporal expression of inflammatory peptides alter the normal response
of masseter muscle to localized injury. Gene transfer into skeletal muscle
provides an approach to define the role of specific gene products in tissue
pathology. Using gene transfer in mice, the action of inflammatory mediators
on the masseter and on masticatory afferents can be directly tested. Elucidation
of the role of inflammatory mediators in masticatory muscles is important
for both understanding the etiology of and designing novel therapeutic strategies
for the treatment of TMDs.