A Magic Bullet for Pain? A Biomarker for Pain? The 2018 North American Pain School Trainees Take the Gloves Off to Make Their Cases

From a unique take on classic rap songs to a “conversation” with the US President, all was fair game at the NAPS debates

Editor’s note: The third North American Pain School (NAPS) took place June 24-28, 2018, in Montebello, Quebec, Canada. An educational initiative of the International Association for the Study of Pain (IASP) and Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), and presented by the Quebec Pain Research Network (QPRN), NAPS brings together leading experts in pain research and management to provide 30 trainees with scientific education, professional development, and networking experiences. This year’s theme was “To Boldly Go… : The Future of Pain Treatment.” Six of the trainees were also selected to serve as PRF-NAPS Correspondents, who provided firsthand reporting from the event, including interviews with NAPS’ six visiting faculty members and summaries of scientific sessions, along with coverage on social media. Here, PRF Correspondent Katelynn Boerner, PhD, a postdoctoral fellow at BC Children’s Hospital, University of British Columbia, Vancouver, Canada, reports on two debates that took place at the 2018 version of NAPS.

On the final evening of the 2018 North American Pain School (NAPS), trainee attendees (a.k.a. “NAPSters”) took to the stage for one final challenge: The Great NAPS Debates, emceed by Jeff Mogil, director of NAPS. Initial secret ballots were cast to determine the audience’s own pre-debate stances. After the closing statements by each side, a show of hands would be taken to determine the final tally of “pros” versus “cons”; the winner would be the team that swayed the most audience members to their side.

Graduate student debate

The first debate was taken on by the graduate student trainees of NAPS, who argued for or against the following resolution: “That sometime in the next 30 years, a ‘magic bullet’ molecule or device will be developed and approved that will be broadly and strongly effective against the symptoms of chronic pain.”

The “pro” team

Michael Chiang, University of Pittsburgh, US, kicked off the opening statements for the “pro” team with a passionate plea, describing the devastating impact of chronic pain, including decreased functioning and detrimental effects on mental health. He argued for investment in new lines of therapeutics to provide people with pain the quality of life they deserve. Chiang said that now is the perfect time to find a magic bullet, citing technological advancements such as brain imaging and genetic tools that have pushed the field to heights previously thought unattainable. He finished by describing NAPSters (except those on the “con” team) as the researchers who will turn the dream of a magic bullet into reality.

Olivia Eller-Smith, University of Kansas Medical Center, Kansas City, US, followed by reminding the audience of other diseases previously thought to be untreatable, such as leprosy, smallpox, scurvy, rabies, and human papillomavirus (HPV). She reminded the audience of NAPS visiting faculty member Judy Watt-Watson’s presentation from earlier that day, where she had described the increasing recognition of the societal burden of pain. Eller-Smith also pointed to the growing awareness of the need to expand pain research funding, with $500 million having been provided recently by the US Congress to the National Institutes of Health (NIH) to fund pain research, with a particular focus on non-addictive drugs and devices (see PRF related news article). Thus, she argued for the equation: rapidly developing technology + increases in funding for, and interest in, chronic pain = a magic bullet.

The “con” team

Not to be outdone by the pro team’s attempts to sway the audience with personal insults, Anne Burke, University of Adelaide, Australia, suggested that her colleagues on the “pro” team were “well-meaning but deluded.” Burke cited numerous interventions that seemed to promise a magic bullet, including cocaine, heroin, opioids, codeine, intrathecal blocks and spinal fusions, none of which have fully lived up to the promise of pain relief or been broadly effective. In fact, she emphasized, these treatments have ranged from moderately effective at best, to downright dangerous.

Following Burke was the University of Tulsa’s Edward Lannon, who provided a slide diagram showing a “brief” (read: extremely complicated) summary of what can go wrong in the pain system. Lannon argued that even if researchers could find a treatment that would address all of these aspects of the chronic pain experience, only 1 in 5,000 compounds in pre-clinical testing make it to market, and it takes, on average, 12 years for a drug to be approved. Therefore, he concluded: it’s not going to happen.

The rebuttals

Rebuttals began with Carleton University’s Annemarie Dedek, from the “con” side, who stressed that while NAPSters have clearly dedicated themselves to the important pursuit of a cure for chronic pain, they are not naïve to the significant challenges facing pain research. She argued that the notion that all the various chronic pain conditions could be addressed with a single treatment is misguided, and spoke of the need to take combination approaches rather than search for a single solution. She encouraged the audience to be realistic, and to remember that a complex problem requires a multifaceted solution.

Candler Paige, University of Texas at Dallas, US, came back to support the “pro” team, calling the “cons” a bunch of “negative Nancys,” and encouraging them to reflect on the numerous treatment innovations over the past 30 years, including triptans and gabapentin.

Closing statements

Valerie Bourassa, McGill University, Montreal, Canada, provided the closing statement for the “pro” team, reflecting on the potential impact that pain researchers can have on patients’ lives, and the importance of maintaining hope. She harkened to the major advances made in the field of amyotrophic lateral sclerosis (ALS) research since the ice bucket challenge of 2014, and wondered why pain research shouldn’t be able to do the same. She concluded with a video of the “pro” team members each doing the ice bucket challenge, set to the music of Journey’s classic song, Don’t Stop Believin’ (provoking much laughter and applause from the audience).

Giovanni Berardi, Marquette University, Milwaukee, US, offered the closing statement for the “con” team, urging the audience not to be fooled, by stressing that the “pro” team arguments had not addressed other factors (such as depression, anxiety, and fatigue) associated with decreased quality of life for people living with chronic pain.

And the winner is…

With a sway of just three audience members to the “pro” side, the “pro” team was declared victorious!

Postdoc debate

Not to be outdone by their junior colleagues, the postdocs took to the stage to debate the following resolution: “That sometime in the next 30 years, a ‘biomarker’ will be discovered that will gain broad acceptance as an objective measure of pain.”

The “pro” team

The “pro” team started strong with Inge Timmers, Stanford University, Palo Alto, US, who pointed to the many accepted biomarkers for other conditions, including blood tests to measure glucose levels for diabetes, temperature to measure fever, and pregnancy tests to measure hormone levels. Timmers reminded the audience of the identification of a brain signature specific to pain (see PRF related news article). She also provided various examples of promising potential biomarkers, including microneurography and skin/nerve biopsies to identify small-fiber neuropathy.

Then, in a presentation for the “pro” team that skilfully weaved strong scientific arguments with rap references from the 1990s, Kate Sadler, Medical College of Wisconsin, Milwaukee, US, highlighted that even the rappers Tupac Shakur and Notorious B.I.G. would agree that a biomarker for pain would eventually be discovered, because “you’ve got ‘til the end of time” and “mo money, mo problems [to solve].” Sadler cited the significant advances in technology over the past 30 years that are pushing pain research forward, including optogenetics, the human genome project, CRISPR gene editing, and functional MRI. She argued that the influx of money from private companies makes the potential for significant advances even greater, and encouraged the audience to look at the glass as half full.

The “con” team

Amanda Stone, Vanderbilt University School of Medicine, Nashville, US, opened for the “con” team by arguing that because biomarkers need to be accurate and observable, the idea that one may be identified in the next 30 years is far-fetched. Stone referenced recent debates about the very definition of pain, noting that if pain researchers cannot even agree on a definition, then they certainly cannot expect to identify an objective biomarker. The audience was reminded of the incredible variability in the pain experience between humans and across cultures, as well as between pain conditions. Stone argued that finding a single biomarker across the population is not reasonable.

She was followed by Staja Booker, University of Florida, Gainesville, US, who reiterated the challenge of finding a biomarker that is unique to pain, timely and replicable, and able to assess the multidimensional nature of pain.

The rebuttals

Boriss Sagalajev, Hospital for Sick Children, Toronto, Canada, began a humorous rebuttal for the “con” team, suggesting that his Estonian and Russian background gave him direct access to the U.S. President. With “Trump” on the phone (thanks to the magic of app technology) to provide his opinion on the debate, Sagalajev said the best approach is to hope for the best (finding a biomarker) but prepare for the worst (not finding one).

“Pro” team rebuttal leader Vijay Samineni, Washington University, St. Louis, US, reminded the audience of other serendipitous scientific discoveries (such as Viagra), suggesting that “chance comes to only prepared minds.” Samineni described how machine learning and artificial intelligence could likely be used to identify a biomarker, and how sources of big data have been used before to address such problems. He urged the audience not to give up.

Closing Statements

Finally, David Ferreira, University of Pittsburgh, US, and Hadas Nahman-Averbuch, Cincinnati Children’s Hospital, US, closed for the “pro” team by urging the the audience not to think too small, pointing to the many companies that are working on biomarkers right now.

Vanderbilt University’s Michelle Failla proved to have a hidden talent as she rapped the closing statement for the “con” team. Here’s just a flavor of it, to the tune of DJ Jazzy Jeff & The Fresh Prince: “In West Philadelphia born and raised, in labs is where I spent most of my days/Chilling out, maxing, relaxing all cool, shooting capsaicin and then making it cool…/I got into one little debate and we all got scared and said: ‘there ain’t no biomarker for pain that’s fair.’”

A curious tally

With the “con” team having managed to swing an additional five audience members to their side, they were declared the winner! This announcement was received with raucous applause. The audience also applauded Mogil for having “picked good questions.”

With the debates concluded, there was little more to do than to toast a highly successful 2018 North American Pain School, new friends, and great science. With spirits high amongst both the winning and losing sides, a wonderful night was had by all (even by the unlucky souls assigned to the 5:45 AM airport shuttle the next morning).

Far be it from this writer to question the highly ethical procedures of the debate count, but it should be noted that the initial count was 18 “pro”/13 “con”, and the final count 15 “pro”/18 “con.” Where the two extra votes came from remains a mystery…

Katelynn Boerner, PhD, is a postdoctoral fellow at BC Children’s Hospital, University of British Columbia, Vancouver, Canada.