Myofascial pain conditions, including those associated with temporomandibular joint and muscle disorder (TMD) affect millions of people. These conditions are extremely difficult to treat, often leaving patients with a poor quality of life. The long-term objective of this application is two-fold: 1) to elucidate novel cellular signaling mechanisms underlying the development of mechanical hyperalgesia, a major symptom associated with myofascial pain conditions such as TMD and 2) to use this scientific endeavor as a training vehicle for acquiring the knowledge and skills needed to become a successful independent pain scientist. P2X3 receptors are nonselective cation channels that have been implicated in nociceptive processing, including the mediation of mechanical hyperalgesia. TRPV1 and TRPA1 (TRPV1/A1) channels have also previously been implicated in the development of mechanical hyperalgesia in muscle. They are suggested to be inflammatory signal integrators following the activation of pro-inflammatory receptors. Preliminary data suggests direct activation of P2X3 induces mechanical hyperalgesia and pretreatment of the same muscle with TRPV1/A1 antagonists inhibits this hyperalgesia. Calcium permeable P2X3 channel activation could lead to the initiation of signaling cascades which results in the activation of kinases such as CaMKII and PKC, which are known to sensitize TRP channels. This study proposes to use behavioral assays, calcium imaging, and biochemical means to characterize the functional interactions between P2X3 and TRPV1/A1. These same techniques will also be used to elucidate the signaling pathways mediating these interactions. The identification of new mechanisms underlying mechanical hyperalgesia during myositis conditions could contribute to alternative treatment strategies for the management of TMD and other muscle pain conditions.

Public Health Relevance

Orofacial muscle pain particularly that associated with temporomandibular joint and muscle disorder affects approximately 12% of the population. The currently available treatments are inadequate because of the ambiguity surrounding the underlying pathology of the condition. In accordance with the missions of the NIDCR and the FOA: PA-10-108 this study proposes to 1) determine novel cellular mechanisms linking purinergic and TRP channels which could serve as future therapeutic targets and 2) provide a vehicle for the development and training of a rising pain scientist.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DE020966-02
Application #
8261843
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2011-03-01
Project End
2012-10-31
Budget Start
2012-03-01
Budget End
2012-10-31
Support Year
2
Fiscal Year
2012
Total Cost
$19,315
Indirect Cost
Name
University of Maryland Baltimore
Department
Other Basic Sciences
Type
Schools of Dentistry
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201