Tiny protein discovery may transform future of pain relief

Researchers have made a surprising discovery about how the brain controls pain. They found a specific pathway the brain uses to switch pain “on,” and identified that neurons can release an enzyme outside the cell that triggers pain signals, without affecting normal movement or other senses. Essentially, the team has uncovered a way to potentially reduce pain while avoiding the serious side effects that come with many existing pain treatments.

The enzyme, identified by the team as vertebrate lonesome kinase (VLK), changes proteins in its proximity in such a manner that elevates pain and intensifies connections linked to memory and learning. Critically, researchers found that in the removal of VLK, for mice post-surgery, this had the effect of significantly diminishing pain experienced. Additionally, through the removal of VLK it was found that normal functioning of both cells and brain was sustained, leading researchers to highlight the breakthrough could pave the way tods safer and more efficient pain treatments across multiple conditions and recoveries.

Sending messages

The work, co-led by Matthew Dalva, director of the Tulane Brain Institute and professor of cell and molecular biology, alongside a coalition of partners, has caught the attention of scientists, pharmaceutical industry and health and aged care sectors across the world. The team, comprised of researchers from nine institutions have identified a completely unknown, until this year, way in which nerve cells send messages.

The encouraging sentiment in the medical community is that this discovery is likely to alter how scientists and the medical community comprehend pain, and powerfully direct the advancement of safer and more efficient treatment of pain.

Outside the cell

Dalva and his co-lead, Ted Price of the University of Texas have articulated that the study highlights that neurons are able to release an enzyme outside the cell, which then trigger pain signals after an injury or surgery. The study, reported and published in Science, also provides further insight into how brain cells reinforce links during moments of memory and learning.

Speaking from his Tulane University platform, Dalva says, “This finding changes our fundamental understanding of how neurons communicate,” continuing, “we’ve discovered that an enzyme released by neurons can modify proteins on the outside of other cells to turn on pain signaling — without affecting normal movement or sensation.”

The study explains that neurons utilise VLK in order to communicate in the area outside of, but in the vicinity of, the cell, where the effect is to change the proteins in the proximity so that signals traveling between nerve cells are influenced.

Broad implications

Through Tulane University messaging Price also explains further implications. “This study gets to the core of how synaptic plasticity works – how connections between neurons evolve,” he contributes, as director of the Center for Advanced Pain Studies, professor of neuroscience at the University of Texas at Dallas’ School of Behavioral and Brain Sciences and a co-corresponding author of the study. “It has very broad implications for neuroscience, especially in understanding how pain and learning share similar molecular mechanisms.”

Of particular interest to providers and clinical heads must be the opportunities for the treatment of pain in far safer ways than previously on offer to the medical community.

Dalva notes that the findings signal the opportunity to pursue safer ways to alter pain pathways through the targeting of enzymes like VLK instead of relying on the widely used route of blocking NMDA receptors. While this route has been effective in influencing communication between nerve cells, it is widely evident in the science and its real-world implementation that there can be grievous side effects when these communications are interrupted.

Better treatment

Dalva weighs in on the findings, in articulating that they provide a novel first example of approach in structuring communications between cell-surface proteins outside of the cell itself. He assesses this could simplify drug development and limit collateral damage in off-target effects as the drug would be prevented from entering the cell.

It is worthwhile for provider and clinical heads to be closely watching the development of this area of research as the implications for the thousands of seniors requiring improved pain management is significant. Through more targeted and safer pain management approaches, not only is it that providers may be able to elevate care and resident quality of life but minimise the cost of treating unintended and grievous side-effects for residents.

Further possibilities

Dalva and the research team also highlight the need for further research from this initial breakthrough. He notes that the next course of action is to assess whether the function of VLK is a mechanism specific to only a few proteins or is a component of a larger and as yet, unappreciated section of biological understanding. His messaging cautiously nudges the possibilities into the realm of significant breakthroughs in highly needed areas, noting understanding the broader functions could reshape treatment possibilities for a wide range of complex neurological and other diseases.

Collaboration is key

Highlighting a model of scientific study and leveraging of talent and resources that Australia’s public personnel, providers and clinical researchers are encouraged to continue and pivot towards, Dalva reinforces the critical nature of collaborative research.

“Our findings were only possible through this kind of collaboration,” Dalva indicates. “By combining Tulane’s expertise in synaptic biology with the strengths of our partners, we were able to reveal a mechanism that has implications not just for pain, but for learning and memory across species.”

As Australia’s generation continues to age, and the needs of care and pain management only increase, the need for safe and targeted options is only going to grow. The need for providers and clinical heads to be closely monitoring advancements in the international space for breakthroughs is worthwhile. The opportunity to leverage skills, time and resources, across sectors, to be at the forefront of advancements is ideal.