The Next Frontier in Pain Treatment May Lie in Changing Its Biology

Pain has become one of medicine's most persistent contradictions. The body needs pain to signal injury, yet for millions of people that warning system can continue long after the original damage has healed. U.S. data found that 24.3% of adults had chronic pain, while 8.5% experienced pain that frequently limited their life or work activities.

The scale of the problem is forcing a rethink of how pain is treated. In May 2026, the U.S. Food and Drug Administration issued draft guidance specifically addressing the development of non-opioid analgesics for chronic pain, reflecting the continuing need for new approaches in a field where therapeutic options remain constrained. The regulatory push follows a broader shift in pain medicine, including the 2025 approval of Journavx, the first drug in a new class of non-opioid medicines for moderate to severe acute pain. However, drugs for chronic pain continue to partially and ineffectively treat pain symptoms.

Acute pain and chronic pain present fundamentally different biological problems. Acute pain can act as a protective signal, encouraging the body to avoid further injury while damaged tissue heals. Chronic pain persists and involves changes within the nervous system that allow pain signalling to continue and spread into responses to sensations that would ordinarily be harmless. This process can be characterized as a loss of control within the pain system, where inflammation and heightened neuronal activity reinforce one another.

The phenomenon is known as central sensitization, and it presents a particularly difficult challenge because several biological processes can become entangled. Continued pain signalling can activate immune cells called microglia, which release inflammatory factors that alter neuronal behaviour. Neurons can then become increasingly excitable, creating a system in which pressure, temperature, or touch may trigger pain. The clinical consequences reach well beyond discomfort, affecting the ability to work and participate in ordinary life. CDC data links chronic pain with reduced quality of life and other substantial health burdens.

That biological problem is the focus of Dr. David Bravo, CEO and co-founder of Pannex Therapeutics, a New York-based biopharmaceutical company developing small-molecule therapies targeting Pannexin-1, or Panx1, to treat chronic pain. Dr. Bravo, who has researched the target for more than a decade, argues that the field needs to investigate what sustains pathological pain after the original injury has passed.

"We're not trying to just stop pain; we're trying to control the cause of that pain," Bravo says. "What is generating this pain, and how can we change the biology that is generating this pathological pain? The answers to these questions are the core of our technology."

Pannexin-1 is a membrane channel involved in cellular signalling. According to Bravo and other researchers, pathological activation of the channel can contribute to ATP release outside cells, immune-cell activation, and inflammatory signalling, while also increasing neuronal excitability. Bravo notes that Pannex Therapeutics has developed a small molecule called PX004 that blocks the channel and influences multiple elements of the pain process through one biological target in animal models.

The company's preclinical findings have produced another question: how long can a biological effect persist after the drug itself has left the body? Dr. Bravo points to animal studies in which PX004 has a relatively short half-life while the observed biological effect has lasted considerably longer after repeated treatment. He views that durability as central to the scientific proposition, alongside clinical potential, while stressing that the findings remain preclinical. "The compound is not only durable in relieving pain, but it also shows superior efficacy compared to the standard of care", Dr. Bravo notes.

Evidence is also where the argument becomes more demanding. Pannexin-1 remains a relatively new therapeutic target, and Dr. Bravo acknowledges that its role in normal human physiology requires further investigation before any clinical conclusions can be drawn. He reports that Pannex Therapeutics has conducted testing involving locomotor function, sedation, coordination, and organ analysis, including extended high-dose animal studies, without observing side effects so far. Dr. Bravo states, "These findings are part of our preclinical program, and they cannot establish human safety yet. That is our next step."

The broader significance lies in the question the research raises. If persistent pain is partly sustained by biological changes within the nervous system, treatment strategies may need to address those mechanisms directly. FDA action in 2025 and 2026 demonstrates that developing safer non-opioid approaches remains an active priority, while the emergence of new targets points towards a wider scientific search for alternatives.

For patients living with chronic pain, the value of that search is ultimately measured in possibilities. "We're not trying to just stop pain," Dr. Bravo says. "We're trying to control the cause of that pain to bring hope to people suffering from it." The potential of their work, in his view, is less about promising a cure and more about determining whether changing the biology of pain can produce persistent relief that lasts beyond the presence of a drug itself.