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Clinical Trial Builds Upon Yale Studies to Provide Proof-of-Concept that Subtype-specific Sodium Channel Blockers can Reduce Pain in Humans

August 03, 2023
by Lakshmi Bangalore

Pain is a pervasive symptom encountered by physicians worldwide and a longstanding medical challenge, particularly against the backdrop of the opioid crisis. However, a study published in the August 3 issue New England Journal of Medicine brings hope for more effective pain control says Yale neuroscientist Stephen G. Waxman in an accompanying editorial that he wrote for the journal.

The publication by Vertex Pharmaceuticals revealed results of a clinical study assessing Nav1.8 blocking drug for patients suffering from postoperative pain. The study demonstrated a significant reduction in pain when compared to placebo, with no apparent safety issues.

The Vertex study builds upon a series of discoveries made by Waxman and his colleagues at Yale beginning in the year 1997. Their research established that Nav1.8 channels play a crucial role in generating nerve impulses in pain-signaling neurons, leading to the prediction that targeting these channels could offer potential relief from pain.

In the editorial, Waxman recounted the history of this type of work, starting with the discovery in the 1950s on sodium channels by Hodgkin and Huxley. Building upon that in the 1990s, investigators around the world, including Waxman and his coworkers at Yale, showed that there are multiple types of sodium channels in our body’s cells. This triggered the questions of whether there might be sodium channels that are expressed specifically in peripheral pain-signaling neurons and not in the heart or brain, and if so, whether targeting such channels might allow reduction in pain without central side effects such as dizziness or confusion.

“The importance of this work is that it is a step toward proof-of-concept that a Nav1.8-selective sodium channel blocker can reduce pain in humans,” notes Waxman. “This work will hopefully spur additional studies on subtype-specific sodium channel blockers. It will not happen tomorrow, or next month, or even next year. But I am confident that, sooner or later, we will have a new class of non-opiate pain medications, fulfilling a very substantial unmet medical need.”

Submitted by Zachary Restifo on August 03, 2023