Chronic nerve pain can be extremely difficult to treat, and many people live with it for months or years.
Researchers at Weill Cornell Medicine and the Burke Neurological Institute are developing a new type of medicine that could one day offer pain relief without the addiction risks linked to opioid drugs.
Nerve pain, also called neuropathic pain, develops when nerves are damaged or stop working normally. People may experience burning, shooting, stabbing, or electric-like pain even when there is no new injury.
The condition can develop after diabetes, infections, injuries, surgery, or some medical treatments. Because damaged nerves can continue sending pain messages to the brain, the discomfort may remain long after the original cause has disappeared.
Current treatments do not work well for everyone. Doctors may prescribe medicines such as gabapentin, which was originally developed to treat seizures, or duloxetine, an antidepressant that can also reduce some types of nerve pain.
These medicines can help some patients, but their effects vary and they can cause unwanted problems such as dizziness, tiredness, or changes in mood. Opioids may also reduce pain, but long-term use can bring risks including dependence, addiction, and overdose.
The researchers therefore looked for a different way to control pain. Their work focused on proteins known as HCN ion channels, which help control electrical activity in nerve cells.
When these channels become too active in damaged nerves, the cells can become unusually easy to trigger. This may cause them to repeatedly send pain signals even when the body is not facing immediate harm.
Targeting HCN channels is challenging because they are not found only in pain-related nerves. They also have important jobs in the brain and heart, so a drug that blocks them throughout the body could cause serious unwanted effects.
Dr. Gareth Tibbs and his colleagues developed an experimental drug called BP4L-18:1:1 to overcome this problem. The drug is designed to act on nerves outside the brain while limiting its effects on other important organs.
The researchers created the compound by modifying propofol, a well-known anesthetic used during medical procedures. They attached a chemical structure that helps prevent the drug from easily entering the brain.
This approach is sometimes compared with putting an anchor on a boat. The added chemical feature helps keep the medicine where researchers want it, allowing it to calm overactive pain-related nerves without producing the strong brain effects associated with propofol.
In experiments with rats, the drug reduced signs of nerve pain when it was given by mouth. The researchers also reported that the animals did not show the unwanted effects that might be expected if the drug strongly affected the brain or heart.
These animal findings are promising, but the treatment is still experimental. A drug that works safely in rats may behave differently in people, so carefully controlled human studies will be needed before doctors could consider using it as a treatment.
The researchers are working toward clinical testing to determine whether the approach is safe and effective in humans. Akelos, a company involved in developing the treatment, is helping move the experimental drug toward further testing.
The work also received support from the Daedalus Fund for Innovation, which helps researchers turn early scientific discoveries into possible medical treatments. The study highlights how changing where a drug can travel in the body may help scientists target pain more precisely.
If future clinical trials are successful, this approach could provide another option for people whose nerve pain does not respond well to existing medicines. It may also help reduce reliance on opioid painkillers by treating abnormal nerve activity without producing the same addiction risks.
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