Researchers at Tulane University in New Orleans have made a significant advancement in understanding pain mechanisms in the brain. Their discovery involves a nerve signaling process that operates outside the cell, effectively flipping a metaphorical “pain switch.” This breakthrough could lead to the development of safer pain medications that provide effective relief without the common side effects associated with current treatments.
The study, published in the journal Science last week, focuses on the role of phosphorylation—an important process regulating proteins. While phosphorylation has been well studied within cells, its function outside the cell remained largely unclear. The team aimed to investigate whether this modification, which occurs on the exterior parts of synaptic proteins, influences how nerve connections communicate or impacts behavior in living organisms.
The researchers identified an enzyme known as vertebrate lonesome kinase (VLK) that facilitates communication between nerve cells outside the cell membrane. When active neurons release VLK, it enhances the function of pain receptors. According to Matthew Dalva, a brain scientist at Tulane and the lead author of the study, this finding “opens up an entirely new way of thinking about how to influence cell behavior.”
By targeting mechanisms that operate externally, rather than requiring drugs to penetrate cells, the study suggests a simpler approach to drug design for pain relief. In experiments where VLK was removed from pain-sensing neurons in mice, the animals did not experience the typical pain following surgical procedures. Conversely, increasing the level of VLK in these neurons heightened their pain responses. Dalva stated, “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.”
This advancement is crucial in reshaping the approach to developing pain medications. Rather than blocking receptors at synapses, which can lead to unwanted side effects, targeting enzymes like VLK could streamline the process of delivering effective pain relief.
Despite the promising nature of these findings, the researchers emphasize that extensive work remains before next-generation pain medications can be realized. Their future research will focus on exploring how broadly this mechanism affects proteins involved in neurological functioning, potentially paving the way for treatments for other brain diseases beyond pain management.
As the implications of this discovery unfold, it highlights the importance of innovative approaches in the ongoing quest for safer and more effective pain relief solutions.
