Program Provides Research Opportunities for Undergraduate Students
By Michael Haederle
Researching Relief
UNM Scientists Developing Novel Antibody Treatment for Chronic Pain
New federal funding for cutting-edge research at The University of New Mexico Health Sciences Center offers the prospect of relief for the one in five Americans living with chronic pain.
A two-year, $1 million grant award from the National Institutes of Health Helping to End Addiction Long-Term (HEAL) Initiative will fund development of an antibody that dampens the pain response in the brain, says contact principal investigator Karin Westlund High, PhD, professor in the Department of Anesthesiology & Critical Care Medicine.
Westlund High, who has spent the past 35 years exploring pain treatments, says there are distinct differences in gene expression in the brains of people experiencing short-term pain versus those suffering from chronic pain – who see increased production of harmful proteins.
The current study focuses on cholecystokinin (CCK), a peptide hormone that lives in the stomach, where it helps with digestion, and in the brain, where it aggravates nerve cells, which have receptors for the molecule.
The cholecystokinin receptor in the brain is tied to pain and emotion – anxiety and depression
“The cholecystokinin receptor in the brain is tied to pain and emotion – anxiety and depression,” Westlund High says. When more CCK is produced, she says, “it starts a big chain reaction involving the nerves and microglia and ends up causing chronic pain.”
This inflammatory response triggers a feedback loop, she says. “Interacting together causes this continual neuronal firing, which then allows inflammation to continue in this vicious cycle.”
Working with a mouse model, Westlund High and dual principal investigators Sascha Alles, PhD, an assistant professor in Anesthesiology & Critical Care Medicine, and former UNM researcher Adinarayama Kunamneni, PhD, now at the Mayo Clinic in Jacksonville, Fla., have developed a small antibody capable of reaching the brain and attaching itself to the neuronal CCK receptor, blocking the effect of the inflammatory hormone.
In mice, the antibody alleviates pain and is effective in preventing the anxiety and depression that often accompanies chronic pain, she says.
The next step will be to “humanize” the mouse antibody, which shares 85 percent of its DNA sequence with humans, by replacing a few of its amino acids so that it matches the human version, she says. That work is being done by Kunamneni under a subaward.
The UNM team will gauge the pain-relieving efficacy of the antibody on neuron-like cells cultured from stem cells collected from human blood samples that have been exposed to CCK. “We can apply the antibody and check the (neuronal) firing rate to see if it will calm them in the dish,” Westlund High says.
The blood samples come from UNM Hospital patients, some of whom are pain free, and others who are experiencing chronic pain, she adds.
Westlund High credits Eugene Koshkin, MD, and Katie Reyes, MD, both associate professors in Anesthesiology & Critical Care Medicine, as well as Justin Baca, MD, PhD, in the Department of Emergency Medicine, and Hossein Mousavi, MD, a resident in the Department of Neurology, with helping to recruit patients.
Under HEAL Initiative guidelines, if the project hits its anticipated milestones in the first two years it can be extended for three additional years and eventually be tested in humans in Phase 1 and Phase 2 clinical trials, Westlund High says.