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Peripheral mechanisms of oral cancer pain in a mouse model

Institution: University of California, San Francisco
Investigator(s): Brian Schmidt, DDS, MD, PhD
Award Cycle: 2003 (Cycle 12) Grant #: 12KT-0166 Award: $265,332
Subject Area: Cancer
Award Type: New Investigator Awards

Initial Award Abstract
In the United States approximately 30,000 new cases of oral cancer are diagnosed each year. All forms of tobacco smoking, including cigarette, pipe and cigar use, are strongly linked to oral cancer. Tobacco increases the risk of oral cancer in a dose-dependent manner. Patients with oral cancer experience severe debilitating pain from the early stages until death. Patients experience significant functional problems related to oral cancer pain including difficulty swallowing, talking and eating. Disruption of oral function leads to a depressed mood and a very poor quality of life. We currently do not understand the underlying biology of oral cancer pain, why it is so severe, and why medications are not able to alleviate these symptoms. Presently, narcotics are the only analgesics available for oral cancer pain. While narcotics, such as morphine, offer some relief, tolerance rapidly develops. Given that oral cancer is often incurable, it is important for research to be focused on the causes of oral cancer pain.

Our research will be one of the first to investigate the underlying mechanisms contributing to oral cancer pain. We plan to use a mouse model to evaluate the impact of pain on oral functioning (drinking and eating). To pursue this aim we will be using innovative behavioral assays to evaluate pain behavior resulting from oral cancer. In addition, we will evaluate the specific biological characteristics of the tumor that contribute to pain and difficulty with oral functioning. A new technique, called TagMan PCR, will be employed to analyze the role of chemical mediators, such as cytokines, in the tumor microenvironment. Thus, we will combine biochemical /genetic analysis with behavioral factors that associated with pain during the progression of the disease.

We anticipate identifying the peripheral factors that make oral cancer pain so severe and debilitating. This will offer insights into possible means of managing these symptoms of oral cancer. The new animal model generated in this study could be used to develop and evaluate analgesic therapies. Ultimately, this will lead to improved overall quality of life for patients with oral cancer.

The development of an oral cancer pain mouse model.
Periodical: Journal of Dental Research Index Medicus:
Authors: Liu SY, Connelly ST, Schmidt BL ABS
Yr: 2004 Vol: 83 Nbr: A Abs: Pg:

Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain
Periodical: European Journal of Pain Index Medicus:
Authors: Schmidt BL ART
Yr: 2007 Vol: 11 Nbr: Abs: Pg: 406-414

Elevated salivary endothelin levels in oral cancer patients - a pilot study. Oral oncology
Periodical: Oral Oncology European Journal Cancer B Index Medicus:
Authors: Schmidt BL ART
Yr: 2007 Vol: 43 Nbr: Abs: Pg: 37-41

Effect of peripheral endothelin - 1 concentration on carcinomainduced pain in mice.
Periodical: European Journal of Pain Index Medicus:
Authors: Schmidt BL ART
Yr: 2007 Vol: Nbr: Abs: Pg:

Validation of the University of California San Francisco Oral Cancer Pain Questionnaire
Periodical: European Journal of Pain Index Medicus:
Authors: Schmidt BL ART
Yr: 2007 Vol: Nbr: Abs: Pg:

Tobacco free workplace policies and low socioeconomic status female bartenders in San Francisco
Periodical: Journal of Epidemiol Community Health Index Medicus:
Authors: Moore RS, Lee JP, Antin TM, Martin SE. ART
Yr: 2006 Vol: 60 Nbr: Abs: Pg: 51-56