Strategic Initiative Fund (SIF)

A Novel Strategy for Effective and Non-Addictive Pain Management

This proposal presents a novel strategy for effective, non-addictive pain management aimed at addressing the major public health and economic burden of acute and chronic pain. Pain affects a large share of adults in the U.S., reduces quality of life, and costs the economy an estimated hundreds of billions of dollars annually. Current pain treatments remain inadequate: opioids are effective but carry serious risks of addiction, overdose, constipation, nausea, dizziness, and dependence, while many non-opioid alternatives have limited efficacy or problematic side effects. The project seeks to develop a safer, non-opioid therapeutic approach that could improve pain treatment while avoiding the addiction risks and other adverse effects associated with current opioid-based care. If successful, the project could establish a new class of non-addictive pain therapeutics and position U-M as a leader in next-generation pain management.

The project focuses on the delta opioid receptor (DOR), a promising but underused target for pain relief. The project’s central hypothesis is that increasing the amount of DOR delivered to the neuronal surface will increase the pain-relieving effectiveness of DOR agonists without increasing adverse effects. The work will build on strong preliminary evidence from the team showing a neuron-specific checkpoint that blocks DOR delivery to the cell surface. Rather than discovering entirely new DOR agonists, the project aims to identify compounds that promote DOR trafficking to the neuronal surface, which could then be combined with DOR agonists. This represents a new therapeutic strategy. The team will screen large compound libraries, use AI and biological validation to identify promising compounds, and optimize them through medicinal chemistry and safety testing, aiming to deliver a lead compound that could impact the quality of life of roughly a fifth of the world's population.