Research reveals alternative to opioids for chronic pain

FEM-1689, a specific σ2R/TMEM97 ligand, eases neuropathic pain.


Researchers at The University of Texas at Austin are progressing in a new approach to treating neuropathic pain. This type of pain, often caused by nerve damage in various body tissues, is challenging to alleviate and can result in sensations like electric shocks, tingling, burning, or stabbing. 

Conditions such as diabetes, multiple sclerosis, chemotherapy, injuries, and amputations are linked to neuropathic pain, affecting millions globally. Current pain medications for this type of pain are moderately effective and carry severe side effects and addiction risks. 

The UT Austin team, UT Dallas, and the University of Miami have identified a molecule that, in mouse trials, reduces hypersensitivity by binding to a protein associated with neuropathic pain. The study is published in the Proceedings of the National Academy of Sciences.

Stephen Martin, the June and J. Virgil Waggoner Regents Chair in Chemistry at The University of Texas at Austin and co-corresponding author of the paper. Said, “We found it an effective painkiller, and the effects were rather long-lived. When we tested it on different models, diabetic neuropathy and chemotherapy-induced neuropathy, we found this compound has an incredible beneficial effect.”

A new compound, FEM-1689, shows promise as a non-addictive alternative to existing pain medications. Unlike opioids, it doesn’t engage opioid receptors. FEM-1689 reduces sensitivity and regulates the integrated stress response (ISR), which is crucial for the body’s injury and disease response. 

Proper ISR regulation promotes healing, while dysfunction can contribute to diseases like cancer and diabetes. The goal is to develop FEM-1689 into a safe and effective drug for chronic pain. NuvoNuro Inc., co-founded by the researchers, received a grant from the NIH HEAL Initiative to develop this potential solution further amid the national opioid crisis.

Theodore Price, a professor of neuroscience at The University of Texas at Dallas and co-corresponding author of the paper, said, “This work is the culmination of a wonderful five-year collaboration with our colleagues at UT Austin and is a great example of academic drug discovery pushing the field of non-opioid pain therapeutics forward.”

This study marks a significant step forward in the pursuit of non-opioid treatments for chronic pain. The collaboration between these institutions, coupled with support from renowned funding bodies, highlights the importance of finding safer alternatives to address the challenges associated with opioid-based pain management. The disclosed potential conflicts of interest reflect a commitment to transparency in advancing research with real-world applications.

Journal reference:

  1. Muhammad Saad Yousuf, Hongfen Yang, et al., Highly specific σ2R/TMEM97 ligand FEM-1689 alleviates neuropathic pain and inhibits the integrated stress response. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2306090120.


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