New Painkiller Could Bring Relief to Millions—Without Addiction Risk

https://www.scientificamerican.com/article/new-pain-medication-suzetrigine-prevents-pain-signals-from-reaching-brain/

The medication initially known as VX-548 blocks sodium channels in nerves, blocking pain signals before they reach the brain

hen doctors ask Sara Gehrig to describe her pain, she often says it is indescribable. Stabbing, burning, aching—those words frequently fail to depict sensations that have persisted for so long they are now a part of her, like her bones and skin. “My pain is like an extra limb that comes along with me every day.”

Gehrig, a former yoga instructor and personal trainer who lives in Wisconsin, is 44 years old. At the age of 17 she discovered she had spinal stenosis, a narrowing of the spinal cord that puts pressure on the nerves there. She experienced bursts of excruciating pain in her back and buttocks and running down her legs. That pain has spread over the years, despite attempts to fend it off with physical therapy, anti-inflammatory injections and multiple surgeries. Over-the-counter medications such as ibuprofen (Advil) provide little relief. And she is allergic to the most potent painkillers—prescription opioids—which can induce violent vomiting.

Today her agony typically hovers at a 7 out of 10 on the standard numerical scale used to rate pain, where 0 is no pain and 10 is the most severe imaginable. Occasionally her pain flares to a 9 or 10. At one point, before her doctor convinced her to take antidepressants, Gehrig struggled with thoughts of suicide. “For many with chronic pain, it’s always in their back pocket,” she says. “It’s not that we want to die. We want the pain to go away.”

Gehrig says she would be willing to try another type of painkiller, but only if she knew it was safe. She keeps up with the latest research, so she was interested to hear earlier this year that Vertex Pharmaceuticals was testing a new drug that works differently than opioids and other pain medications.

That drug, a pill called VX-548, blocks pain signals before they can reach the brain. It gums up sodium channels in peripheral nerve cells, and obstructed channels make it hard for those cells to transmit pain sensations. Because the drug acts only on the peripheral nerves, it does not carry the potential for addiction associated with opioids—oxycodone (OxyContin) and similar drugs exert their effects on the brain and spinal cord and thus can trigger the brain’s reward centers and an addiction cycle.

In January Vertex announced promising results of clinical trials of VX-548, which it is calling suzetrigine, showing that it dampened acute pain levels by about one half on that 0-to-10 scale. The company is applying for U.S. Food and Drug Administration approval for the drug this year.

Other pain drugs that target sodium channels are now being developed, some by firms motivated by Vertex’s success. Navega Therapeutics, led by biomedical engineer Ana Moreno, is even using molecular-editing tools such as CRISPR to suppress genes involved in chronic pain. “We are definitely hopeful that we can replace opioids, and that’s the goal here,” she says.

One in five U.S. adults—51.6 million people as of 2021—is living with chronic pain. New cases arise more often than other common conditions, such as diabetes, depression and high blood pressure. Yet pain treatments have not kept pace with the need. There are over-the-counter pills such as aspirin, acet­aminophen (Tylenol) and nonsteroidal anti-inflammatories (NSAIDs) such as Advil. And there are opioids. The glaring inadequacy of existing medications to alleviate human suffering has fueled the ongoing opioid epidemic, which has led to more than 730,000 overdose deaths since its start.

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