In a significant advancement in brain science, researchers from Tulane University in New Orleans have identified a novel nerve signaling mechanism that activates a ‘pain switch’ outside the cell. This discovery could pave the way for safer pain medications that provide relief without the common side effects associated with traditional treatments.
The research team, led by brain scientist Matthew Dalva, revealed that the process of phosphorylation—typically understood as a cellular activity—also occurs outside cells in a way that influences how pain receptors function. The scientists aimed to determine the role of this modification on the exterior parts of synaptic proteins and its impact on the signaling of nerve connections in living organisms.
Their findings indicate that nerve cells interact through an enzyme called vertebrate lonesome kinase (VLK). When active neurons release VLK, it enhances the functionality of pain receptors. Dalva stated, “This opens up an entirely new way of thinking about how to influence cell behavior and potentially a simpler way to design drugs that act from the outside rather than having to penetrate the cell.”
The researchers conducted experiments on mice, where they noted that eliminating VLK from pain-sensing neurons resulted in a lack of the expected post-surgery pain response, while still allowing normal sensation. Conversely, increasing VLK levels heightened pain responses. This discovery underscores the potential for an enzyme released by neurons to modify proteins on the exterior of other cells, effectively turning on pain signaling without interfering with normal movement or sensation.
The implications of this research are substantial, suggesting a shift in how pain management drugs can be developed. By targeting enzymes like VLK, rather than blocking receptors at synapses—which can lead to adverse effects—scientists may find a more effective path to delivering pain relief.
Despite the promising nature of this breakthrough, the researchers caution that further investigation is necessary to fully explore the broader effects of VLK on proteins related to neurological functioning. Future studies will aim to assess how this discovery might extend to the treatment of other brain diseases beyond pain.
This study was published in the journal Science last week, marking a pivotal moment in the understanding of pain mechanisms and drug development. As research continues, there is hope that next-generation pain medications could emerge from these findings, improving outcomes for patients while minimizing side effects.
