Translational Research and Tool Development

July 30, 2021
2:00 pm - 4:00 pm
CSRB 4th floor seminar room, 4939 Childrens Pl, St. Louis, MO 63110

Instructors: Dr. Copits and Dr. Ruyle

Translational pain research using human neurons (Dr. Copits)
Chronic pain is a disabling disease with limited treatment options. While animal models have revealed important aspects of pain neurobiology, therapeutic translation of this knowledge requires a detailed understanding of these cells and pain signaling pathways in humans. To do this, we have pioneered the use of human nervous system tissue for physiological testing of pain pathways in research labs. We established a collaboration with a local organ donor network, where we surgically extract sensory neurons and spinal cord tissue from donors. Back in the lab we process the tissue for our experiments. This approach enables genetic
sequencing efforts to characterize human neuronal phenotypes and physiological testing to better understand basic biological processes directly in human neurons. We hope that this reverse translational approach will lead to better identification of drug targets and the validation of new therapies for pain relief.

Developing a closed loop oximeter-naloxone reservoir to prevent opioid overdoses lethal outcomes (Dr. Ruyle)
Opioids are frequently used to treat acute and chronic pain, but are prone to misuse and addiction. One serious consequence of opioid addiction is a potentially lethal impairment of breathing. Intravenous administration of fentanyl produces profound and sustained inhibition of breathing known as opioid-induced respiratory depression (OIRD). While the specific mechanisms through which this occurs are not completely understood, it is believed that opioids exert powerful effects on mu opioid receptors (MORs) located in brainstem cardiorespiratory nuclei. Opioid-induced respiratory depression can be reversed with the opioid receptor antagonist Naloxone. While this treatment can be effective, it must be given in a timely manner and requires the presence of someone else to administer the drug. Our lab is part of a joint collaboration working to develop a wireless, implantable oximeter that chronically measures tissue oxygen saturation. The device has a reservoir containing naloxone, which is released upon detection of reduced oxygen saturation. This device provides a life-saving dose of naloxone without the need for intervention by another party, and could significantly reduce mortality.