Non Addictive Medication for Pain Revealed

According to new research, an experimental medicine fine-tuned to a specific pain pathway might alleviate post-surgery symptoms, which could someday offer an alternative to highly addictive opioids.

The pill, known for the time being as VX-548, targets a specific sodium channel that is exclusively active in the body’s peripheral sensory nerves, where it aids in the transmission of pain sensations to the brain. The assumption is that blocking the channel will alleviate pain without causing major systemic adverse effects, such as the risk of addiction and abuse associated with opioids.

In an early trial, researchers discovered some intriguing evidence that the medicine can alleviate post-surgery discomfort.

Among 577 individuals undergoing bunion surgery or tummy tucks, those given the highest dose of VX-548 saw higher pain reduction in the next 48 hours than those given placebo pills. And the side effects, including headache and constipation, were mild.

The findings, which were published in the New England Journal of Medicine on August 2, are not the final word on the medicine. A phase 3 experiment is currently underway to compare the efficacy of VX-548 to that of a typical opioid painkiller.

“But these findings are an important step forward in showing proof-of-principle,” said Dr. Stephen Waxman, a professor of neurology and neuroscience at Yale University School of Medicine.

Waxman, who was not engaged in the trial, contributed a commentary to the findings that provides an overview of the science underlying the experimental medicine.

“Sodium channels are the molecular batteries that allow neurons [nerve cells] to communicate,” Waxman explained.

The idea of inhibiting sodium channels to interrupt pain signaling is not novel or unusual. Waxman claims that regular novocaine operates in this manner.

However, novocaine and other comparable medicines, such as lidocaine, are “nonselective” in blocking sodium channels. If they were taken as a pill, they would impact all sodium channels, including those in the heart and brain. As a result, the medications are administered via injection into the location where pain relief is required.

Not long ago, no one realized that sodium channels solely functioned in the peripheral sensory nerves. However, the finding of numerous sodium-channel genes boosted the possibility of such channels, according to Waxman. Scientists have detected three so far: 1.7, 1.8, and 1.9.

Vertex Pharmaceuticals, based in Boston, is developing a novel medication that targets the 1.8 channel.

Dr. James Jones and colleagues at Vertex and numerous US medical institutes conducted two experiments to examine if this translates into alleviation from acute pain: One study comprised 303 individuals undergoing abdominoplasty (tummy tuck). For 48 hours after surgery, they were randomly randomized to receive VX-548 (high or moderate dose), a conventional opioid (hydrocodone plus acetaminophen), or placebo pills.

The other experiment included 274 bunion surgery patients. They, too, were randomized at random to either VX-548 (in one of three doses), hydrocodone/acetaminophen, or placebo for 48 hours.

Only the highest dose of the medicine outperformed placebo tablets in terms of reducing patients’ pain intensity levels over two days.

The experiment was not intended to compare VX-548 to hydrocodone/acetaminophen, but there were some encouraging results, according to Dr. Mark Wallace, a pain medicine specialist at the University of California, San Diego.

Wallace adds in a second editorial published alongside the report that the experimental medicine appeared to have less negative effects. In addition, fewer people on VX-548 stopped taking medication because it didn’t work, compared to individuals on opioids.

But, Wallace cautions, “limited conclusions” can be made about the drug’s pain-relieving effects compared with opioids. He described the study as “an early foray into an exciting new class of drugs in a difficult field.”

In the context of an ongoing opioid crisis, an effective pain reliever with a low potential for addiction would be appreciated. According to Waxman, based on the mechanism of action, VX-548 is unlikely to be addictive.

He did, however, emphasize that much more research is needed. This covers big-picture questions like whether targeting several peripheral sodium channels could be more effective at relieving pain.

While the most recent study focused on post-surgical pain, there are other, more difficult-to-treat types of pain.

According to a Vertex spokeswoman, the company has begun an early trial of VX-548 for neuropathic pain. This is discomfort from nerve degeneration, such as diabetic neuropathy.

Waxman stated that there is a “great need” for new neuropathic pain medicines, and that peripheral sodium channels should be explored as potential therapy targets. However, such therapy would be in the future.

“I’m confident that we will have a new class of nonaddictive pain medications,” Waxman stated. “But it will take some time.”

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