Thesis Title

Characterization of an in Vivo Model of Temporomandibular Joint Inflammation

Date of Graduation

Fall 2007


Master of Science in Biology



Committee Chair

Paul Durham


trigeminal nerve, nitric oxide, protons, MAP kinase, gap junction

Subject Categories



Activation of trigeminal nerves is involved in temporomandibular joint (TMJ) inflamation and pain transmission. The proinflammatory molecule nitric oxide (NO) and protons are implicated in the underlying pathology of temporomandibular joint disorders. The goal of this study was to investigate gap junction activity and identify MAP kinases activated in neurons and glia in response to NO/protons. Initially, cell bodies of neurons providing sensory innervation of the TMJ (V3 region), as well as the V1 and V2 regions, were identified by retrograde labeling with the fluorescent dye True Blue. To identify signal transduction pathways activated by NO/protons in trigeminal ganglia, the effect of injection of the NO donor SNP at pH 5.5 into both TMJs on MAP kinases was determined by immunohistochemistry. Low levels of active ERK, JNK, and p38 were localized in the cytoplasm of untreated trigeminal neurons. However, increased levels of active ERK and p38, but not JNK, were detected in V3 neuronal cell bodies and adjacent satellite glial cells 15 minutes and 2 hours following bilateral TMJ injection. Unlike ERK, p38 levels remained elevated 24 hours after injection. Somewhat unexpectedly, increased ERK and p38 levels were also detected in neurons and satellite glia located in V2 and V1 regions of the ganglion. The MAP kinase phosphatases MKP-1, MKP-2, and MKP-3 were also found to be increased in response to NO/protons. Additionally, NO/protons facilitated movement of True Blue dye from neurons to surrounding glia, indicating increased gap junction activity. Results from my study provide evidence to support a role of NO/protons in mediating neuronal and glial cell activation in trigeminal ganglion that is likely to contribute to TMJ pathology and contribute to peripheral sensitization within the ganglion.


© Stacy E. Freeman