November 25, 2012
An article by by Drs. David K. Lam and Brian L. Schmidt of the NYU College of Dentistry’s Bluestone Center for Clinical Research made the cover of the October 10, 2012, issue of The Journal of Neuroscience.
Dr. David Lam is a post-doctoral fellow at UCSF. Dr. Dongmin Dang, Jianan Zhang, and Dr. John C. Dolan from NYU Cancer Pain Laboratory also contributed to the article, “Novel Animal Models of Acute and Chronic Cancer Pain: A Pivotal Role for PAR2.”
According to Dr. Lam, while modern cancer therapies allow cancer patients to live longer, they now face new challenges from severe and chronic cancer-induced pain. “The major impediment for developing new treatments for cancer pain has been our limited knowledge of the basic mechanisms that drive cancer pain,” says Dr. Lam.Dr. Lam’s research investigates these mechanisms by observing the role of protease activated receptor 2 (PAR2) in the progression of pain from acute to persistent to chronic levels using three novel preclinical models. These models provide a solution to the lack of adequate cancer pain models required to study the molecular and neural pathways that generate and maintain cancer pain.
While previous research suggests a role for PAR2 in pain, Dr. Lam’s models go beyond the existing models which utilize reflex responses as dependent pain measures and are unable to reflect the temporal and anatomical progression of cancer pain. The preclinical models in this study parallel the anatomical, temporal, and functional progression of pain and impairment experienced by humans with head and neck cancer.
Specifically, Dr. Lam found that the interactions between serine proteases and PAR2 induce acute and chronic cancer pain, and chronic pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in the peripheral nerves. Most strikingly, cancer pain remained undeveloped in PAR-2 deficient models. Thus, targeting PAR2-serine protease interaction can help with the treatment of acute cancer pain and prevent chronic cancer pain. These findings have significant implications for targeted therapy for cancer pain.