March 07, 2014
In a poster presentation at the 30th Annual Meeting of the American Academy of Pain Medicine, researchers from the University of New England identified a surprising early link that could ultimately open new avenues for the treatment of chronic pain, a serious public health problem with major economic and societal costs.
The researchers found initial confirmation that a novel scaffold protein previously unassociated with the mu opioid receptor (MOR) regulates MOR-induced signaling activation. The MOR is the target of opioid drugs like morphine and is an important mechanism for pain regulation in the body.
The investigators in the March 7th presentation noted that decades of research aimed at discovering new, safer and more effective drugs to treat chronic pain have met with limited success.
“The most surprising result of this study was that we were able to find a novel regulatory protein that no one had ever associated with the MOR or pain, and show in cells that this protein regulates MOR signaling,” said senior study author John Streicher, PhD, assistant professor at the University of New England in Biddeford, Maine.
Two UNE undergraduate students—and now full-time UNE laboratory technicians—Katie Edwards ’13 and Justin LaVigne ’13, and University of Maine graduate student Emmanuel Moses-Fynn, are co-authors of the study.
“What this finding may allow us to do is design new drugs to target the MOR to produce pain relief with reduced side effects. More broadly, understanding the molecular mechanism of MOR signaling will open up many new strategies for improved drug design.”
Once identified, candidate proteins can be manipulated in cells and the effects on MOR signaling determined, as was done with one candidate protein in this study, Streicher explained. Previous research work has validated this basic approach and though promising, has been limited so far because the signaling complex and regulators of opioid receptors have not been defined with sufficient detail, which would be crucial for success, according to Streicher.
From the data gathered in the study presented today, the investigators plan to identify a list of potential signaling regulators of the MOR and will further test the candidate proteins for their ability to regulate pain and MOR activity. Studies using live animal models to address these questions with the regulatory protein already identified will get under way within the next few months.
Streicher notes that the path from research to drug discovery and development is a long one. Moving from pre-clinical studies to applying for Investigational New Drug (IND) status with the Food and Drug Administration, to conducting the necessary human trials can take more than 10 years. The current research result is in the very beginning stage of this process, but Streicher says, “It is exciting to build something from the very beginning. UNE has a unique entrepreneurial culture where we have the freedom to pursue new ideas and collaborate with one another. It’s a very collegial research environment.”
Streicher extends that collaboration to his own lab, where three UNE undergraduate students are actively involved in his research. His undergraduate researchers are exploring different aspects of opioid receptor function and regulation, each with their own unique project. UNE has a strong culture of undergraduate participation in research, where many faculty, including Dr. Streicher, support their students to develop as independent scientists and often present their work at national and regional conferences.
“Ultimately, what we hope to accomplish is to develop an array of drugs using different molecular strategies to achieve a desired effect,” Streicher adds. “If successful, patients may one day be able to select specific drugs for difficult-to-treat chronic pain states like neuropathic pain, or to reduce specific –or all– side effects.”
The study was funded through a pilot project grant (P20GM103643) to UNE from the Centers of Biomedical Research Excellence, a division within the National Institutes of Health.
The American Academy of Pain Medicine is the premiere 2,400-member medical association for pain physicians and their treatment teams. Now in its 30th year of service, the Academy’s mission is to optimize the health of patients in pain and eliminate it as a major public health problem by advancing the practice and specialty of pain medicine through education, training, advocacy and research. Information is available on the Academy’s website.