Rethinking Acute Pain Management: The Next Frontier of Pain Relief with James Hackworth – Episode 266

James discusses why undertreated severe pain carries risks of its own, how researchers are exploring the NOP receptor system and what acute pain trials can reveal about new analgesics.

Acute pain treatment presents a difficult balance: inadequate pain relief can have serious consequences of its own, while stronger analgesics such as opioids carry severe risks of physical dependence, misuse and life-threatening respiratory depression.

In this episode of the Xtalks Life Science Podcast, host Dr. Mohammad Ali speaks with James Hackworth, PhD, Cebranopadol Development Lead at Tris Pharma, about how researchers are approaching this crucial balance and what clinical trials can tell us about the next generation of pain medicines.

James witnessed the devastating impact of opioid addiction up close. His experiences, along with his interest in the science of pain, drew him to the field.

“People think of pain as only a comfort issue,” James explained. When severe pain is not well treated, prolonged pain signaling can, in some cases, lead to lasting changes in the nervous system through neuroplasticity.

When pain signals fire for too long, the nervous system can get “stuck.” Even after the physical injury has fully healed, it may continue firing as if the damage were still there, much like the phantom limb pain that can occur after an amputation.

Researchers are also looking beyond traditional opioid pathways for ways to relieve pain while reducing treatment-related risks. James highlighted the nociceptin (NOP) receptor system, a “regulatory system” in the body.

But why does he bring this up?

While traditional opioids can provide powerful pain relief, they can also trigger dopamine release in the brain’s reward pathways, contributing to euphoria and abuse potential.

James explained that stimulating the NOP system alongside opioid receptors can act like a biological “brake,” helping maintain analgesic effects while attenuating effects associated with abuse potential, respiratory depression and physical dependence.

James also demystified why acute pain trials rely on bunion removals and tummy tucks (abdominoplasty). These standardized procedures serve as “proxies” for hard-tissue (bone) and soft-tissue pain. Testing a compound in both models can help indicate how it may perform across other surgical and non-surgical acute pain settings.

Listen to the full episode to hear James discuss how researchers determine whether pain relief is “clinically meaningful.”

The podcast is available for streaming every other Wednesday on Apple Podcasts, Spotify and wherever you stream your podcasts.

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