Date of Graduation

Summer 2008

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Paul Durham

Keywords

trigeminal nerve, TNF-α, gap junctions, MAP kinases, MKPs

Subject Categories

Biology

Abstract

The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has been implicated in the underlying pathology of joint disorders including those of the temporomandibular joint (TMJ). Trigeminal nerve activation is important in mediation of inflammation and pain within the TMJ. The goals of this study were to study gap junction activity within the trigeminal ganglion (TG) and to determine the cellular signaling pathways activated in response to TNF-α injection into the TMJ capsule. Initially, the retrograde tracer dye True Blue was used to identify the neurons innervating the TMJ capsule. To determine the gap junction activity in response to TNF-α injection into TMJ, dye movement was monitored using fluorescent microscopy. Following TNF-α injection, the dye moved from neuronal cell bodies to surrounding satellite glial cells, indicative of increased gap junction activity. To identify cellular signaling pathways activated in the TG by TNF-α, immunohistochemistry was used to determine the effects of TNF-α injection into TMJ on mitogen activated protein kinases (MAP kinases). While low levels of active p38, ERK and JNK were seen in the V3 region of the ganglia from untreated control animals, increased levels of active p38 and ERK, but not JNK, was observed in both the neurons and satellite glial cells in ganglia from animals treated with TNF-α for 30 minutes and 2 hours. Surprisingly, the increased levels of p38 and ERK were also seen in the V2 and V1 regions of the ganglia. Levels of MAP kinase phosphatases (MKPs) MKP-1, MKP-2, and MKP-3 were also increased 30 minutes and 2 hours after TNF-α treatment. This study provide evidence that TNF-α activation of sensory neurons in the TMJ leads to changes in MAP kinase signaling pathways in neurons and satellite glia within the TG. These TNF-α mediated cellular events are likely to play an important role in peripheral sensitization, and therefore inflammation and pain associated with TMJ pathology.

Copyright

© Srikanth Damodaram

Campus Only

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