Chronic Compression of the Trigeminal Ganglia

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DESCRIPTION (provided by applicant): Trigeminal neuralgia (tic douloureux) is a devistatingly painful craniofacial disease, characterized by intense stabbing pains of the face which may be elicited by light touch. In the majority of cases, the pain can be traced to chronic compression of the trigeminal nerve roots by a blood vessel, leading to demyelination of the compressed roots. These compression and myelination changes may then alter Na+ channel density along the nerve root, possibly leading to ectopic discharges, and abnormal fiber-to-fiber transmission of impulses. Although some Na+ channel blocking anti-seizure drugs are helpful in the short-term, many patients end up having invasive neurosurgery to decompress the nerve root. Even surgery however, typically only provides temporary relief. A primary issue limiting the development of new, more effective therapies, has been the lack of an animal model which accurately simulates trigeminal neuralgia. One of the two main goals of RFA-DE-07-006 "New Models of Pain Relevant to the Trigeminal System" is to "stimulate the development and utilization of novel animal models of chronic orofacial pain conditions. As an adjunct to these two goals, this Initiative also encourages the development of novel measures of pain in patients and animals that are non-invasive and objective and that permit a behavioral or functional assessment of pain." The goal of the proposed research fits closely with this goal, in that we plan to develop an accurate, predictive animal model of trigeminal neuralgia. Our preliminary work has shown that transcranial placement of a biocompatible superabsorbant polymer next to the trigeminal nerve root pushes the root against the bone, providing a means of non-inflammatory chronic compression, simulating human pathology. The technique is relatively non-invasive and simple to perform. Furthermore, these experiments have shown that these animals demonstrate behavioral and electrophysiological changes that are highly consistent with the symptoms and signs of trigeminal neuralgia. We propose to further characterize this model, providing clear endpoints to test potential therapies and a means to examine mechanisms underlying trigeminal neuralgia. These mechanistic studies, in turn, can lead to the determination of new targets for pharmacdceutical development, as well as for gene therapy approaches.