Pain is easy to understand until it isn’t. A stubbed toe or sprained ankle hurts, but it makes sense because the cause is clear and the pain fades as you heal.
But what if the pain didn’t go away? What if even a breeze felt like fire, or your leg burned for no reason at all? When pain lingers without a clear cause, that’s neuropathic pain.
We are neuroscientists who study how pain circuits in the brain and spinal cord change over time. Our work focuses on the molecules that quietly reshape how pain is felt and remembered.
We didn’t fully grasp how different neuropathic pain was from injury-related pain until we began working in a lab studying it. Patients spoke of a phantom pain that haunted them daily – unseen, unexplained and life-altering.
These conversations shifted our focus from symptoms to mechanisms. What causes this ghost pain to persist, and how can we intervene at the molecular level to change it?
More than just physical pain
Neuropathic pain stems from damage to or dysfunction in the nervous system itself. The system that was meant to detect pain becomes the source of it, like a fire alarm going off without a fire. Even a soft touch or breeze can feel unbearable.
Neuropathic pain doesn’t just affect the body – it also alters the brain. Chronic pain of this nature often leads to depression, anxiety, social isolation and a deep sense of helplessness. It can make even the most routine tasks feel unbearable.
About 10% of the U.S. population – tens of millions of people – experience neuropathic pain, and cases are rising as the population ages. Complications from diabetes, cancer treatments or spinal cord injuries can lead to this condition. Despite its prevalence, doctors often overlook neuropathic pain because its underlying biology is poorly understood.
Neuropathic pain can be debilitating.
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There’s also an economic cost to neuropathic pain. This condition contributes to billions of dollars in health care spending, missed workdays and lost productivity. In the search for relief, many turn to opioids, a path that, as seen from the opioid epidemic, can carry its own devastating consequences through addiction.
GluD1: A quiet but crucial player
Finding treatments for neuropathic pain requires answering several questions. Why does the nervous system misfire in this way? What exactly causes it to rewire in ways that increase pain sensitivity or create phantom sensations? And most urgently: Is there a way to reset the system?
This is where our lab’s work and the story of a receptor called GluD1 comes in. Short for glutamate delta-1 receptor, this protein doesn’t usually make headlines. Scientists have long considered GluD1 a biochemical curiosity, part of the glutamate receptor family, but not known to function like its relatives that typically transmit electrical signals in the brain.
Instead, GluD1 plays a different…
