Block that conversation, and you dial down the pain signal
For the roughly one-third of Americans living with chronic pain, relief has long come tethered to risk — the risk of dependence, of diminishing returns, of trading one suffering for another. Researchers at NYU have now proposed a different bargain: a gene therapy that does not silence the body's pain machinery outright, but instead interrupts a precise molecular conversation within nerve cells, quieting pain signals without the collateral damage that has made opioids so costly a solution. The work, still awaiting human trials, carries the particular weight of a discovery that has held across species — suggesting that what was learned in a laboratory mouse may one day matter to a person.
- Chronic pain touches one in three Americans, yet the dominant treatments — opioids — carry their own devastating costs, leaving millions trapped between suffering and dependency.
- The NaV1.7 sodium channel has long been a tantalizing target for pain researchers, but every attempt to simply shut it down has failed, stalling progress for years.
- NYU's Rajesh Khanna found a way around the wall: rather than blocking the channel itself, his team disrupted the regulatory protein CRMP2's ability to communicate with it — a precise intervention made possible by a binding site unique to NaV1.7.
- Delivered via an adeno-associated virus already trusted in human medicine, the gene therapy reversed pain in mice within one to ten days across multiple pain types, including chemotherapy-induced neuropathy.
- Results held across rodents, primate cells, and human cells in culture — a consistency that has prompted the founding of two biotech companies and patents, signaling that the path toward clinical trials is being actively built.
A research team at NYU College of Dentistry's Pain Research Center has developed a gene therapy that quiets chronic pain by interrupting a molecular conversation inside nerve cells — offering a fundamentally different path for the one-third of Americans living with chronic pain who have long had few options beyond opioids.
The therapy targets NaV1.7, a sodium ion channel long known to govern pain sensation. People born unable to activate it feel no pain; those with overactive versions suffer chronically. The instinct has always been to block the channel — but years of attempts have failed. Rajesh Khanna, who leads the center, chose a different approach: rather than attacking NaV1.7 directly, he targeted its relationship with a regulatory protein called CRMP2. The two molecules communicate constantly, shaping how much sodium flows through the channel. Disrupt that conversation, Khanna reasoned, and the pain signal dims without destroying the channel's other functions.
The key was finding where CRMP2 attaches to NaV1.7 — a binding site unique to this channel among its nine-member family. That specificity means a therapy targeting this interaction could reduce pain signaling without cascading side effects. The team engineered a small peptide that mimics this binding region and inserted it into an adeno-associated virus — a delivery vehicle already proven safe in treatments for blood and eye disorders. Once carried into neurons, the peptide blocks the CRMP2-NaV1.7 exchange and dampens pain. In mice, the therapy reversed sensitivity to touch, heat, and cold, as well as chemotherapy-induced neuropathy, within one to two weeks.
The results held across rodents, primate cells, and human cells in culture — a consistency that meaningfully raises the prospect of human translation. Khanna's team has since founded two biotech companies and secured patents on the method. Human trials remain ahead, but for patients — particularly cancer survivors navigating neuropathy — this research represents a genuinely new kind of possibility.
A team at NYU College of Dentistry's Pain Research Center has engineered a gene therapy that quiets chronic pain by intercepting a conversation between two molecules inside nerve cells. The work, published in the Proceedings of the National Academy of Sciences, offers a fundamentally different approach to a problem that has frustrated pain researchers for years: how to treat the roughly one-third of Americans living with chronic pain without reaching for opioids.
The target is a sodium ion channel called NaV1.7. Scientists have known for years that this channel matters—people born with mutations that block it feel no pain at all, while others with mutations that flood the channel with sodium experience debilitating chronic pain. The obvious move would be to simply shut NaV1.7 down. Researchers have tried for years. It hasn't worked. Rajesh Khanna, who directs the Pain Research Center, took a different path. Instead of attacking the channel directly, he decided to disrupt the relationship between NaV1.7 and a regulatory protein called CRMP2. The two molecules communicate constantly, modulating how much sodium flows through the channel. Block that conversation, Khanna reasoned, and you dial down the pain signal without destroying the channel itself.
The breakthrough came when Khanna's team identified the exact spot on NaV1.7 where CRMP2 attaches. This region is unique to NaV1.7—CRMP2 doesn't bind readily to the eight other sodium channels in the same family. That specificity matters enormously. It means a therapy targeting this interaction could affect pain signaling without disrupting other critical functions those channels perform elsewhere in the body. When the researchers removed that binding region in laboratory tests, CRMP2 could no longer regulate the channel. The door had closed.
To translate this discovery into a treatment, the team engineered a peptide—a small piece of genetic material—that mimics the region where CRMP2 binds. They inserted this peptide into an adeno-associated virus, a delivery vehicle already proven safe in human medicine for treating blood disorders and eye diseases. The virus carries the genetic instruction into neurons, where it blocks the CRMP2-NaV1.7 conversation and dampens pain signals. In mice experiencing various forms of pain—sensitivity to touch, heat, and cold, as well as neuropathy from chemotherapy—the therapy worked. Within one to two weeks, pain was reversed.
The researchers replicated these results across multiple species: rodents, primate cells, and human cells in culture. That consistency suggests the approach might actually work in people, though human trials remain ahead. Khanna and his colleagues have already founded two biotech companies to develop the technology further, and they hold patents on the method. The long-term goal is clear: a gene therapy that cancer patients and others suffering from chronic pain could receive to reclaim their lives. For a population that has endured decades of inadequate options and the dangers of opioid dependence, this represents a genuinely different kind of hope.
Citações Notáveis
We found a way to take an engineered virus containing a small piece of genetic material from a protein that all of us have and infect neurons to effectively treat pain.— Rajesh Khanna, director of NYU Pain Research Center
There is a significant need for new pain treatments, including for cancer patients with chemotherapy-induced neuropathy. Our long-term goal is to develop a gene therapy that patients could receive to better treat these painful conditions.— Rajesh Khanna
A Conversa do Hearth Outra perspectiva sobre a história
Why does blocking the conversation between these two molecules work better than just shutting down the channel itself?
Because NaV1.7 does other important things in the body. If you destroy it entirely, you might solve pain but create new problems. By just interrupting one specific interaction, you're turning down the volume on pain without silencing the whole system.
And CRMP2 only talks to NaV1.7, not the other sodium channels?
That's the key discovery. Yes. The binding site is unique to NaV1.7. That's why this works—you get precision. You're not hitting eight different channels by accident.
How long until people can actually receive this treatment?
The animal work is done. They've tested it in rodents and confirmed it works in human cells grown in the lab. But human trials take time. Years, probably. The science is solid, but medicine moves carefully.
What about the virus itself? Isn't that risky?
It's a fair question, but adeno-associated viruses have already been used safely in humans for other gene therapies. This isn't a new delivery method—it's proven. The novelty is what's being delivered.
For someone in chronic pain right now, what does this mean?
Not an immediate answer, unfortunately. But it means the research community is moving away from opioids toward something more targeted. It means someone is thinking about their specific problem in a new way.