A Path Towards Better Pain Treatments and Outcomes: A Conversation with Dennis Turk

Editor’s Note: The first-ever North American Pain School (NAPS) took place June 26-30, 2016, in Montebello, Quebec, Canada. An educational initiative of the International Association for the Study of Pain (IASP); Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); and the Quebec Pain Research Network (QPRN), NAPS brought together leading experts in pain research and management to provide 30 trainees with scientific education, professional development, and networking experiences. Six of the trainees were also selected to serve as PRF-NAPS Correspondents, who provided first-hand reporting from the event, including summaries of scientific sessions and interviews with NAPS’ six visiting faculty members, along with coverage on social media. This is the second installment of interviews from the Correspondents, whose work is featured on PRF and on RELIEF, PRF’s new sister site for the general public.

Dennis Turk, PhD, is the John and Emma Bonica Endowed Chair in Anesthesiology and Pain Research; Professor of Anesthesiology and Pain Medicine; and Research Director of the Center for Pain Research on Impact, Measurement, and Effectiveness (C-PRIME), at the University of Washington in Seattle, US. Turk’s research has focused on the assessment and treatment of a range of chronic pain conditions, including fibromyalgia, whiplash-associated disorders, headache and temporomandibular disorders, clinical trial design, comparative effectiveness research, subgroup identification and treatment matching, and coping and adaptation. Turk also helped to create Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), which develops consensus reviews and recommendations for improving the design, execution, and interpretation of clinical trials of treatments for pain. Turk sat down with PRF-NAPS Correspondent Luke Legakis, an MD/PhD student at Virginia Commonwealth University, Richmond, Virginia, US, to discuss his current research interests, including IMMPACT, clinical trials of fibromyalgia treatments, and studies in geriatric populations, among other topics. Below is an edited transcript of their conversation.

What was your path to pain research?

I went to graduate school at the University of Waterloo in Ontario, Canada, because there was a professor there, Donald Meichenbaum, whose research I loved and who I wanted to work with. As fortune would have it, it turned out that I met his sister, who is now my wife, and that was another incentive to go there because I had met him through family, not just through research.

I moved to Canada, and the concern that he and I both had was whether it would look awkward for me, being his brother-in-law, to have him as my mentor. We thought that wasn’t a good idea, and so that’s how I joined my other mentor, a professor named Ken Bowers. He was doing pain research using hypnosis, and the most important thing I was learning with him was that perceptions of pain could be manipulated. I became fascinated with pain, especially as I learned more about its complexities.

I then did a summer clerkship for four months at Toronto General Hospital in a pain clinic, and I had a chance to see real patients who were experiencing pain. From both the laboratory work and clinical work that I did, I decided that I really wanted to do something about pain. Although I knew I couldn’t eliminate all the pain that people had, I wanted to find a way to help people cope and adapt to it, given that they’re going to have a pain problem potentially for the rest of their lives. That became my passion.

What are you working on now?

One area I’m involved with is clinical trials in patients with fibromyalgia. Fibromyalgia is typically characterized by widespread pain all over the body, with lots of comorbid, characteristic symptoms. There is a range of different treatments that have been used, and while they all have some effect, none of them are sufficient. What we are doing now is asking, rather than just using one of these treatments, whether we can maximize the benefit by using a combination of treatments.

For example, we now have an NIH [U.S. National Institutes of Health] grant looking at the combination of tramadol with cognitive-behavior therapy (CBT). The reasoning behind utilizing tramadol is that it has dual-action; at lower doses it has an anti-depressive effect, and at higher doses it has an analgesic effect, so potentially the patient could benefit from both effects. By itself, tramadol has been shown to provide about a 30% reduction in pain, and CBT also has about a 30% reduction—could we synergize those? Our study is now in its fourth year, and we’re looking to see if, in fact, we’ll have an additive benefit of having both the active drug as well as the CBT. Maybe we can get better than the 30% benefit for either alone by using that combination.

What other areas are you focusing on?

Another major research area involves IMMPACT [Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials] and ACTTION [Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks]. IMMPACT came from discussion I had with Robert Dworkin at the University of Rochester. We were sitting at the 2002 IASP [International Association for the Study of Pain] World Congress on Pain, and we were bemoaning that there were all of these studies on pain, but we couldn’t bring them together and compare them because they had different diagnoses, criteria, and outcomes (see PRF related news story). We decided to have a meeting that would bring pain researchers together to see if we could come up with some agreed-upon criteria that should be used in clinical trials. We had the meeting and it was quite successful; people felt it was very useful. We published the IMMPACT paper, and then people said there were a lot of other areas where some consensus was needed on the design of trials, and on how to analyze the data, for example. We agreed, and now IMMPACT is in its 16th year.

ACTTION came about from participation of the FDA [US Food and Drug Administration], who we had invited to come to all of the IMMPACT meetings because they are involved with outcomes in clinical trials. They said that they liked what we were doing by publishing all of these papers and bringing people together, and asked if we would take a broader approach on other aspects related to improving the outcomes of those trials. IMMPACT is now a part ACTTION.

What considerations should be made when determining whether a drug relieves pain?

In the United States, getting a drug approved by the FDA requires that certain, very rigorous standards be met, but they are limited standards. It’s typical, for instance, to see trials lasting three months for chronic pain conditions. The pharmaceutical industry has very good researchers, but they also know the reality that clinical trials are expensive studies to do, so if the FDA says a trial should last three months, they’ll do trials lasting three months, because they want to get a drug approved. The trouble is that chronic pain conditions go on for years, so why would you expect that three months’ worth of any drug that’s approved would have beneficial effect years down the line? There’s just no consideration of that right now.

The FDA also has a very strict guideline about outcome criteria. Right now, their criteria for an analgesic drug is that it reduce pain, so therefore the primary outcome is pain reduction or elimination, or less medication use, but it’s all about pain. Yet pain is only one outcome, and the association between reducing pain and improving function is very poor. Researchers and the FDA—and they are discussing this—need to realize that in addition to a primary outcome measuring pain, you might also want a composite outcome, or co-primary outcomes; you may need to think about function as well as pain, and not have pain be the exclusive outcome.

You also have an interest in geriatrics. How did that come about?

I was fortunate enough to recruit a collaborator, Kushang Patel from the National Institute on Aging, who is an epidemiologist doing research on physical functioning in aging. He became interested in pain, so he and I spend a lot of time now working not only on epidemiologic studies looking at pain outcomes, but also developing measures of physical function. Whereas typically the measures of physical function in pain studies have been self-reported measures, he is very knowledgeable about some of the other measures and of actigraphy, which is a way of objectively measuring activity.

We now have some clinical trials ongoing in a community-dwelling geriatric population of people with knee osteoarthritis. We’re trying to see if we can use exercise programs and behaviorally oriented programs to improve functioning, and to deal with what is a unique problem for our older population, which is fear of falling. One of the concerns that people who are aging are most worried about is losing independence —being in a nursing home, for example, or being unable to get out of their home—and therefore they also are very well aware that if they fall, they’re more likely to have an injury that can lead to those consequences.

What happens is that because they have pain and are afraid of falling, they do less, and as they do less, they become more disabled. What we’re trying to understand is whether we can deal not only with the pain, but also with the fear of engaging in activities to keep people functioning. The two pilot projects in this area we have going on now, similar to the clinical trials for fibromyalgia I mentioned earlier, are looking at combination treatments, but this time for a geriatric, community-based population. Here, we don’t want to do this in a clinic; the idea is to see if we can put these treatments into community centers, YMCAs, and other places of that kind.

Looking at the pain field more broadly, what is the biggest challenge for pain research today?

The biggest challenge we’ve had is how to disseminate information from funded clinical trials and translate it into clinical practice. In the United States, there is also a concern that the funders make the decisions, so if I could show them that a rehabilitation program could be more cost-effective and have clinical outcomes that were beneficial both to the patient and to the payer, the question becomes whether the funders would be interested in that, rather than more surgery, nerve blocks, or spinal cord stimulation. Those procedures, while they may reduce symptoms, are terribly expensive, rarely cure anyone, and end up causing more problems.

The challenge is that we bring people in for a clinical trial, do some type of intervention such as physical therapy or behavioral rehabilitation, observe them for a certain number of weeks or number of sessions, and then they’re done—but they continue to live with pain because neither of these interventions cures anyone. What they do, potentially, is reduce some of the symptoms, and help people function better, but they don’t eliminate pain. But once the study is done, we tell patients to keep doing all the things we’ve taught them to do, but we know that people won’t—just look at how hard it is for people to keep New Year’s resolutions, for instance, or to reduce smoking or obesity.

There are a number of people working on developing ways to enhance adherence, and I think that’s going to be huge. Until we have a cure, and as long as people are going to live for decades with their pain problems, even though these may be reduced, we need to figure out how to keep people doing these interventions, and how to deal with flare-ups, bad days and the process of aging itself.

Another big challenge is getting young people into the pain field, which is a difficult and very complex area of research—how do you find young people willing to devote their careers to working in this area? I don’t think we’re going to find a cure for pain any time soon, and there are other lucrative things young scientists could be doing, so how do we get them to study pain? It’s a challenge for all of us, to understand how to keep the momentum and enthusiasm going that moves research forward. If we don’t have young people, who are going to be future leaders, stay interested in the research, then the field is going to wither away.

What advice do you have for young researchers?

There are 24 hours in the day, and you can only spend so much time on your academic pursuits. You have to sleep too, so that leaves a finite number of hours to do things—and every time you add something in one area, you’re subtracting from another area of your life. I would like young researchers not to forget that someday they will be 65 or 70 or 75 years old and looking back on their careers and asking themselves if they really got what they wanted out of their lives. You’ve got to find balance, and it’s hard because there are a lot of other demands on you, such as having a family or a significant other, and these are the easiest things to sacrifice, unfortunately—because the grant deadlines aren’t going to change. So that’s where wisdom meets passion.

My other advice for young researchers is to make sure you find mentors who are going to mentor you not just to self-aggrandize themselves, but because they really have a commitment to seeing you develop.

Thanks for speaking with PRF.

Thank you.

Additional reading

Using a biopsychosocial perspective in the treatment of fibromyalgia patients.
Turk DC, Adams LM
Pain Manag. 2016 May; 6(4):357-69

Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations.
Edwards RR, Dworkin RH, Turk DC, Angst MS, Dionne R, Freeman R, Hansson P, Haroutounian S, Arendt-Nielsen L, Attal N, Baron R, Brell J, Bujanover S, Burke LB, Carr D, Chappell AS, Cowan P, Etropolski M, Fillingim RB, Gewandter JS, et al.
Pain. 2016 May 5.

Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations.
Taylor AM, Phillips K, Patel KV, Turk DC, Dworkin RH, Beaton D, Clauw DJ, Gignac M, Markman JD, Williams DA, Bujanover S, Burke LB, Carr DB, Choy EH, Conaghan PG, Cowan P, Farrar JT, Freeman R, Gewandter J, Gilron I, et al.
Pain. 2016 Apr 7

Pain intensity rating training: results from an exploratory study of the ACTTION PROTECCT system©.
Smith SM, Amtmann D, Askew RL, Gewandter JS, Hunsinger M, Jensen MP, McDermott MP, Patel KV, Williams M, Bacci ED, Burke LB, Chambers CT, Cooper SA, Cowan P, Desjardins P, Etropolski M, Farrar JT, Gilron I, Huang I-Z, Katz M, et al.
Pain. 2016 May; 157(5):1056-1064.