The long-term objective of our NIH-supported research is to elucidate the central mechanisms and neuroplastic processes underlying acute and chronic dental and orofacial pain conditions and their control. Our recent data have revealed tooth pulp-induced neuroplastic changes in nociceptive brainstem neurons of the rat subnucleus oralis and caudalis that involve N-methyl-D-aspartate (NMDA) mechanisms. These changes appear to reflect a process analogous to the """"""""central sensitization"""""""" recently described in spinal nociceptive pathways that has been implicated in the development of the hyperalgesia and spread and referral of pain that may occur after injury and inflammation of peripheral tissues. The relative importance of oralis and caudalis to the central expression and modulation of these nociceptive phenomena is however still unclear, and there is very limited information available of thalamic nociceptive mechanisms and neuroplasticity associated with the central mediation of pulp pain. Given the well-documented role of caudalis in orofacial pain mechanisms and its direct projections to both thalamus and oralis, and the limited information on brainstem and thalamic neuroplasticity, it is proposed to use single neuron recordings in anesthetized rats, to address Hypothesis I: The pulp-induced neuroplastic changes in subnucleus oralis nociceptive neurons can be manifested in ventrobasal thalamic neurons and are dependent on subnucleus caudalis; and Hypothesis II: Pulp-evoked neuronal discharges but not pulp-induced neuroplastic changes in ventrobasal thalamic neurons are primarily dependent on subnucleus oralis. The properties of ventrobasal thalamic neurons will be documented before and after molar pulp stimulation in rats with or without disruption of caudalis or oralis to determine if neuroplastic changes are manifested in thalamic nociceptive neurons and non-nociceptive neurons and if these changes an other neuronal properties are dependent on caudalis or oralis. Hypothesis III: Pulp-induced neuroplastic changes in subnucleus oralis nociceptive neurons but not pulp-evoked oralis neuronal discharges are dependent on subnucleus. The properties of oralis neurons will similarly be assessed to determine if the pulp-induced oralis neuroplastic changes and other neuronal properties are dependent on caudalis. This project will provide further new insights into the central processing of pulp afferent information and its relationship to orofacial pain and inflammation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE004786-23
Application #
6379702
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (01))
Program Officer
Kousvelari, Eleni
Project Start
1978-01-01
Project End
2002-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
23
Fiscal Year
2001
Total Cost
$155,763
Indirect Cost
Name
University of Toronto
Department
Type
DUNS #
259999779
City
Toronto
State
ON
Country
Canada
Zip Code
M5 1-S8
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Kumar, Naresh; Cherkas, Pavel S; Chiang, C Y et al. (2012) Involvement of ATP in noxious stimulus-evoked release of glutamate in rat medullary dorsal horn: a microdialysis study. Neurochem Int 61:1276-9

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