The long-term objective of our NIH-supported research is to elucidate the central mechanisms and neuroplastic processes underlying cute and chronic dental and orofacial pain conditions and their control. We have previously shown the role of the trigeminal (V) brainstem complex in processing afferent inputs from the tooth pulp as well as cutaneous and deep tissues, and V brainstem neuronal neuroplasticity resulting from pulp deafferentation or loss of small afferent fibers. We have also recently documented that application of the C-fiber excitant and inflammatory irritant mustard oil (MO) to deep craniofacial tissues can also induce neuroblastic changes in rat V nociceptive neurons reflecting a process analogous to the """"""""central sensitization"""""""" recently described in spinal nociceptive pathways; they are accompanied by increases in electromyographic (EMG) activity of jaw muscles and involve N-methyl-D- aspartate (NMDA) and opioid neurochemical mechanisms. These central changes and mechanisms have been implicated in the development of the hyperalgesia and spread and referral of pain that are characteristic of injury and inflammation to deep tissues. We have now acquired preliminary data revealing that application of MO to the rat tooth pulp can also induce increased jaw muscle EMG activity that is modulated by an opioid mechanism. This acute pulp inflammatory model and our expertise with the V brainstem complex allow us to address whether C-fiber excitants inducing pulp inflammation also induce neuroblastic changes analogous to those of central sensitization of V brainstem neurons and involving NMDA and opioid mechanisms. Over the next 3 years, we will address Hypothesis I: The application of the C-fiber excitant and inflammatory irritant mustard oil (MO) to the rat molar pulp induces neuroplastic changes in subnucleus caudalis and subnucleus oralis neurons reflected in altered receptive field (RF) and response properties. The RF and response properties of caudalis and oralis neurons will be documented before and after MO application to determine the effects on V brainstem neurons of a C-fiber excitant producing acute pulp inflammation. Hypothesis II; The altered receptive field (RF) and response properties of caudalis and oralis neurons induced by the application of the C-fiber excitant and inflammatory irritant mustard oil (MO) to the rat molar pulp involve excitatory amino acid (EAA) mechanisms. The NMDA antagonist, MK-801 will be administered systemically to determine if the neuroplastic changes are dependent upon NMDA mechanisms. Hypothesis III: The altered receptive field (RF) and response properties of caudalis and oralis neurons induced by the application of the C-fiber excitant and inflammatory mustard oil (MO) to the rat molar pulp involve an opioid mechanism. The opiate antagonist naloxone will be administered systemically to determine of the neuroplastic changes involve an opioid suppressive mechanism. Since dental pain of an acute or chronic nature is commonly associated with inflammation (e.g. pulpitis), such studies of potential central V neuroplasticity will provide new insights into brainstem neural mechanisms underlying inflammatory-related pain from the pulp.
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