Editor’s Note: The following is an excerpt from “Fresh Approaches” in the latest edition of UT Dallas Magazine.
From left: Drs. Ted Price BS’97, Greg Dussor and Zak Campbell devote their research to relieving pain.
In an era of increased opioid-related addiction and deaths, the way we treat all pain patients is under the microscope.
From 2013 to 2016, the National Institutes of Health (NIH) spent more than $1.9 billion to fund pain research. At stake, the well-being of more than 25 million U.S. adults who in 2012 reported suffering from daily chronic pain — a subset of which is affected by the ongoing opioid crisis.
According to January 2018 data from the NIH, more than 90 Americans each day die after overdosing on opioids — prescription pain relievers, heroin and synthetic opioids like fentanyl. Between 21 and 29 percent of chronic-pain patients who are prescribed opioids misuse them, and 8 to 12 percent develop an opioid-use disorder.
Three University of Texas at Dallas scientists — Drs. Ted Price BS’97, Greg Dussor and Zak Campbell — are attacking this ever-present problem from varied angles, each with his own focus, background and motivation for understanding it, reducing it and pre-empting it.
The Pain That Lingers
Dr. Ted Price knows pain in every sense of the word. As a researcher, he has studied the signaling pathways in pain-sensing neurons for 15 years.
Read More
The Pain Beyond Our Reach
Dr. Greg Dussor’s pursuit is to improve our understanding of migraine.
Pinpointing Pain’s Origins
Dr. Zak Campbell’s team has devised a way to block creation of the proteins that set pain in motion.
As an athlete, he has endured the aftereffects of a spinal injury. And as an advocate, he’s spoken with federal officials and worked with programs to address the opioid addiction epidemic plaguing our nation.
Price’s current quest is to find a permanent replacement for opioids — to find something that truly treats chronic neuropathic pain.
“Opioid use for chronic pain shouldn’t exist. The drugs don’t work,” said Price, a Fellow, Eugene McDermott Professor in the School of Behavioral and Brain Sciences. “But there’s no alternative, and I think physicians feel morally obligated to offer something.”
Price describes clinical pain as a situation where nerve cells, or neurons, become extraordinarily sensitive. He’s focused on the molecular signals that turn up the amplification. In 2011, Price published work identifying the AMP-activated protein kinase (AMP-K) enzyme as a negative regulator of that amplifier — it turns the knob back down.
“In the years since we’ve published, about 100 papers have been written confirming that AMP-K activators reduce pain,” he said.
A Safe, Inexpensive Drug
Price advocates for repurposing existing medications, and it just so happens that an omnipresent drug fits the bill for his project.
“We found that metformin, a drug used for Type 2 diabetes, has really strong effects as an AMP kinase activator,” Price said. “It is the most widely prescribed drug in the world. It’s very safe and very inexpensive.” With momentum building toward a prospective clinical trial for metformin, Price describes himself as “extremely hopeful.”
“If we find something that suggests we could use metformin for pain associated with chemotherapy, that’s amazing,” he said. “That situation is becoming increasingly common. We could prevent a tremendous amount of suffering, then perhaps do more trials in other populations to increase the scope of these drugs.”
At the same time, Price has a backup plan. Through an NIH grant, CerSci Therapeutics — a company Price helped to form to find non-opioid pain solutions — is working on more potent AMP-K activators for treatment of post-surgical pain.
“We want to replace opioid use. That’s when most people become addicted, through a prescription for acute pain related to surgery,” Price said. “Pharmaceutical company Merck studied long-term dosing of AMP-K activators and proved these compounds are safe. I think there’s a great chance these compounds can be approved for a variety of diseases.”
A Slow Battle
Regardless of the strength of the evidence, Price knows that supplanting opioids in the market will be a tough task. “The oldest pain medicines humans have are aspirin, marijuana and opioids,” Price said. “Can we eliminate reliance on them in the short term? Probably not. It may be that there’s simply nothing better than opioids for acute pain — for the first 24 hours after surgery or a horrific injury. But we can do better after that.”
From his experience with advocacy on the issue, Price knows it’s a slow battle.
“It’s going to take a coordinated effort, and a lot of political will. But we’re now equipped with data on two major fronts that moves the needle,” he said. “We know now that using opioids for acute pain increases the incidence of chronic pain. Secondly, opioid use for chronic pain really doesn’t do anything, and probably makes people even worse.”
Price can speak on that topic from experience. In 2006, a degenerative disk he’d dealt with since he was 17 pushed into his spinal cord, causing intense, debilitating pain “so severe that I could see it — a bright red glow.”
“I thought that I knew what really severe pain was like. I didn’t,” he said. “I’m just flat-out lucky that it went away. I had surgery that had a 50-50 chance at working, and it did. I can’t imagine having a productive life with that. I can’t imagine my wife having a productive life with me being in that state.”
With that understanding came a sense of empathy. “There’s a stigma against people who have chronic pain,” Price said. “Many are accused of being drug addicts or drug seekers, which is completely unfair.”
Though he was already studying neuropathy when his injury happened, Price says his plight did change his sense of urgency for the problem — and his interest in taking his quest beyond the laboratory. He’s been involved in federal programs on the opioid crisis, including as a co-chair on the Federal Pain Research Strategy’s work group on the transition from acute to chronic pain.
If he’s to leave his mark in this pursuit, Price knows his advocacy is as likely as his research to make the difference.
“It’s totally ridiculous to think that I’m going to be the one to solve this problem,” he said. “It’s going to be hundreds, if not thousands, of people working together. But somebody has to champion that. And I, along with a couple other people around the country, have put in a lot of effort to do that. And what happened to me had a big impact.”