Demystifying Pain: Insights on Pain Management and Breakthroughs in Pain Relief with Dr. William Schmidt
As an orthopedic surgeon, we deal with two fundamental problems. Can we restore function to people after an injury? And can we decrease pain either from an acute injury or a chronic problem such as low back pain, a meniscus tear, a broken bone, or arthritis? Function is often easy for us. We can replace a joint, reconstruct an ACL, fix a broken bone, or simply have a patient recover from a muscle strain by going with time, ice, and physical therapy. Pain is much more complex and indeed the physiology and psychology of pain is the most challenging part of my job, particularly in the management around the initial injury and surgery. Indeed, the amount of pain that patients may have is probably the biggest concern of patients and family members alike when thinking about an upcoming surgical procedure.
For today’s 6 to 8 weeks podcast, we brought in a leading expert on pain. Dr. William Schmidt is an expert on pain and has worked over the past three decades in developing pain medications across several classes of therapeutics. We talk about the mysteries of Tylenol and how it may be extra effective when combined with other drugs, some of the nuances and dangers of opiate medications such as oxycodone, fentanyl, and Vicodin. We also talk a little bit about new drugs coming down the pipeline. He touches on drugs that work on a particular sodium channel, which is called the NAV 1.8, and drugs that function by inhibiting this channel. This drug, which was featured in the New England Journal of Medicine last year, is particularly promising as a brand new class of drug that could help acute pain clinically as soon as next year, which is really, really exciting.
As always, the transcript has been edited, but listen in on our podcast, or watch on YouTube for the complete details!
From Childhood Accidents to Cutting-Edge Pain Management: An Interview with Dr. Schmidt
Dr. Feeley: What first sparked your interest in pain management, way back when you were deciding on your career path?
Dr. Schmidt: You know, it all started when I was just five years old. I had a pretty rough accident in kindergarten, falling off a climbing platform onto a playground full of tricycles. I broke both bones in my left arm, and from that experience, I realized that most doctors didn’t really understand pain or how to manage it. That incident planted a seed in my mind, and after graduating from UC Berkeley, I took what I thought was a short summer stint at UC San Francisco’s pharmacology department. There, I worked with Dr. E. Leong “Eddie” Wei, one of the world’s leading researchers on opioid analgesics. That was when I truly fell in love with pain management and decided to devote my career to it.
Feeley: Most people, hearing about your broken bones, would assume you’d end up an orthopedic surgeon!
Dr. Schmidt: Believe me, I considered it! I had plenty of orthopedic issues growing up—broken bones, sprains—you name it. But pain management fascinated me more. There’s something about understanding how the body processes pain and how to manage it that captivated me from the start.
Feeley: Speaking of pain management, when patients come in after surgery, their biggest concern is often the postoperative pain. Can you explain what’s happening in the body that causes this pain?
Dr. Schmidt: That’s a great question, and to answer, let’s start with a rare condition—congenital insensitivity to pain. These individuals don’t feel pain the way most people do. While they can sense heat and cold, they don’t experience pain, which leads to some severe consequences. Many don’t live past their mid-20s because pain signals serve a protective function—alerting us to injury or infection. Now, through studying genetic mutations linked to this condition, we’ve identified several key genes, one of which, the SCN9A gene, produces a protein called Nav1.7. This protein is integral to pain perception. Inhibiting this specific sodium channel has been a focus for drug development, and we’re getting close to breakthroughs in new treatments for pain.
Feeley : For the average patient who isn’t genetically insensitive to pain, how do more familiar drugs like anti-inflammatories work in comparison to opioids?
Dr. Schmidt: Anti-inflammatory drugs, like aspirin and ibuprofen, work by inhibiting an enzyme called cyclooxygenase (COX). There are two types: COX-1 and COX-2. These enzymes play a role in creating the perception of inflammation and pain. By blocking these, anti-inflammatories reduce the body’s inflammatory response. Opioids, on the other hand, work differently. They bind to receptors in the brain, changing how the brain interprets pain. Opioids don’t stop pain at its source like anti-inflammatories—they simply alter how pain is experienced.
Feeley: Speaking of opioids, they’re incredibly effective, but also dangerously addictive. Why is that?
Dr. Schmidt: In some people, opioids cause euphoria, which can make them highly addictive. But not everyone reacts the same way—some people feel awful after taking opioids. The problem is that over time, regular use of opioids can lead to tolerance, where more of the drug is needed to achieve the same effect. This can lead to dependence and addiction. Fortunately, research into safer opioids and pain management alternatives has been promising. For example, new drugs targeting specific opioid receptors without causing the euphoric high—or the deadly respiratory depression that can accompany overdose—are on the horizon.
Feeley: That’s incredible! But how far are we from seeing these safer drugs in routine surgeries like ACL or rotator cuff repairs?
Dr. Schmidt: The process to develop new analgesics is slow—12 to 14 years, on average. However, there’s hope. The NIH’s HEAL Initiative (Helping to End Addiction Long-term), which started in 2018, is pouring billions into advancing pain medicine. One exciting development is a new Nav1.8 inhibitor that may soon be approved by the FDA, which could offer a powerful alternative to opioids for post-surgical pain.
Feeley: That’s amazing. Before we wrap up, can we expect advances in figuring out which patients are more prone to opioid addiction beforehand?
Dr. Schmidt: We’re working on it. Through biomarker and genetic research, we’re hoping to one day tailor pain management to individual patients, reducing addiction risk. But that’s still years away. In the meantime, starting with low opioid doses and combining them with non-opioid options, like anti-inflammatories and acetaminophen, can help minimize risk.