Peripheral tissue damage or nerve injury to somatosensory neurons in rats results in functional and cytochemical changes in sensory neurons and pain behaviors that resemble clinical neuropathic states. The long-term objectives of our research are to understand the role of voltage-gated calcium channels in the peripheral and central mechanisms associated with neuropathic pain. The proposed studies offer several unique opportunities. First, the studies will examine the normal pattern of expression and localization of voltage-gated calcium channels in the trigeminal ganglion and in teeth. Second, changes in the expression of these channels will be assessed in two models of neuropathic pain. The first model is coronal pulp exposure, which leads to pulpal necrosis and chronic inflammation and the second model is unilateral inferior alveolar nerve crush. Use of these two models will allow comparisons to be made between tissue and nerve damage. Each experiment will also assess changes in calcium channels compared to terminal marker proteins (syntaxin and synaptotagmen) as well as several neuropeptides (substance P and calcitonin gene-related peptide) at various post-operative time points. Our hypotheses are that discrete changes in calcium channels will occur and will differ for the two models. Behavior tests will allow us to determine whether or not those changes have behavioral correlates. The trigeminal system provides an ideal model system in which to investigate these changes since its somatotopic organization is well known and changes which are known to occur following lesions of the trigeminal system differ from those of injured segmental nerves. The studies outlined in this proposal will lead to a greater understanding of the changes in calcium channels that occur after trigeminal sensory nerve injury and will have important implications for future drug therapies for inflammatory and neuropathic pain.
