Editor’s note: The fourth North American Pain School (NAPS) took place June 23-28, 2019, in Montebello, Canada. Six of the NAPS trainees were also selected to serve as PRF Correspondents, who provided firsthand reporting from the event, including interviews with six visiting faculty members and summaries of scientific sessions, along with coverage on social media. At NAPS 2019, PRF Correspondent Kyle Vader, a PhD student in rehabilitation science at Queen’s University, Kingston, Canada, interviewed visiting faculty member Troels Jensen, MD, DMSc. Jensen is professor of neurology at Aarhus University Hospital in Denmark, as well as professor of Experimental and Clinical Pain Research and director of the International Diabetic Neuropathy Consortium at Aarhus University. He also served as president of the Scandinavian Association for the Study of Pain from 1989 to 1994, and president of the International Association for the Study of Pain from 2005 to 2008.
Here, Jensen talks about his research, what has led to his success as a pain investigator, and even his chance meeting with “Lady Diana.” Below is an edited transcript of the conversation.
Tell me a bit about yourself and your path to pain research.
After I started my MD, I went to France for a year where I studied clinical neurology and became very fascinated by the ability to make diagnoses of the nervous system with very simple tools and your knowledge of physiology and anatomy. This led to my appointment, later on, in a clinical program of neurology at different hospitals in Denmark.
During my clinical training, I also had the chance to go into research full time, causing some delay in my final clinical education. I went into research following a meeting in Denmark, where I heard a talk about pain processing by Patrick Wall. I was completely carried away and knew that pain should be my topic of research; I became totally fascinated by it.
At the same time, I had the chance to study spinal nociceptive reflexes in rats in the Department of Psychopharmacology at Aarhus University in Denmark, where I looked at how these reflexes were modulated by monoamines. This was at the beginning of the 1980s, where I had just read the first publications about intrathecal administration by Tony Yaksh at the Mayo Clinic in the US, and how this technique allows for focal administration of drugs to the spinal cord. My interest was in the role of descending modulation by monoamines from the brainstem to the spinal cord.
I undertook these initial studies with a colleague, without any supervision, and we soon needed specific guidance. I had communications with Tony, and it soon became clear that I could not get any further in my research without having a visit to his lab. This resulted in a fascinating and very productive research period, thanks to extraordinary inspiration from Tony, and I finished my thesis.
What specific experiments did you do?
As I mentioned, my focus was on descending pain control with a focus on the role of the monoaminergic system, which includes serotonin, noradrenaline, and dopamine. We made injections of morphine and glutamate into key areas of the brainstem and tried to antagonize the antinociceptive effect by administering dopaminergic, serotonergic, and noradrenergic antagonists into the spinal cord, This work on descending pain modulation complemented similar studies by researchers including Howard Fields, Allan Basbaum, Jerry Gebhart, Ron Dubner, Jean-Marie Besson, and others.
What happened next?
After these exciting studies in basic pain research, I became more interested in clinical neurology, and gradually had to give up basic research. However, I wanted to use the knowledge I learned about the neuropharmacology of pain and apply it to humans, particularly to human diseases of the nervous system. This led to a series of studies looking at pain in many different conditions within neurology, including limb amputations, painful neuropathies, trigeminal neuralgia, spinal cord injury pain, multiple sclerosis, and stroke, and seeing how pain in these different conditions might be connected.
We clarified the epidemiology of these conditions and tried to dissect some of the mechanisms underlying central and peripheral neuropathic pain. I’ve been lucky to have support from various grants so that I could hire various PhD fellows. Over the years, I’ve had over 30 PhD fellows who have completed their PhD programs—all excellent individuals who have really done the hard work behind the studies over the years.
What has led to your success as a pain researcher?
Hard work is one thing, and the other is focus; I concentrated my work on the importance and characteristics of pain in different neurological disorders. It was important for me to understand the mechanisms that are responsible for pain in neurological diseases. There are clearly commonalities, but there are also remarkable differences. This is an aspect that has been neglected because many people just talk only about neuropathic pain in general, as if it is all the same. It is not!
I didn’t want to start new basic research because it’s a very competitive area, and it’s difficult to keep up with all the new molecular mechanisms. But what I did want to do was use my knowledge about new pharmacology from animal studies and apply this to humans and see how we can treat neuropathic types of clinical pain using principles derived from the basic sciences.
You’re currently the director of the International Diabetic Neuropathy Consortium. Can you tell me a bit about that, and what the organization does?
In 2015 I received a grant I had been working on for a long time from the Novo Nordisk Foundation. It enabled me to start an international collaboration, where I established contact with neurology colleagues around the world. Eva Feldman, who is at the University of Michigan, has been looking at diabetic neuropathy for many years. David Bennett, at the University of Oxford, is another wonderful international collaborator. Together with them and colleagues at our university in Aarhus and the University of Southern Denmark, we’re looking into diabetic neuropathy pain, including the questions of who develops neuropathy following diabetes, and who develops pain on top of the diabetic neuropathy.
It’s the same principle we had been looking at before: Why is it that some patients develop pain when they have a specific disease or condition? And what are the mechanisms for that pain? Our approach is that this international collaboration is multidisciplinary, meaning it involves basic as well as clinical science.
At NAPS, you gave a talk on risk factors for the development of persistent pain. What did you want the NAPS trainees to take away from your talk?
It was a clinical talk. I wanted to emphasize that there are some mechanisms common to all sorts of pain, but that we have to take the underlying disease and its specific pathophysiology into account. Until now there has been too much “scratching the surface,” a fact that may also explain why, so far, we have not been better at identifying and documenting disease-modifying treatments.
This is an area where basic research could be helpful for understanding more about the mechanisms underlying hypersensitivity. For example, will it always be that peripheral sensitization develops into central sensitization? What are the roles of central modulating effects? What are the roles of emotional-affective factors? Which parts of the brain and which brain mechanisms can trigger central sensitization?
Also, we have neglected the role of emotional, psychological, and social factors in the development of pain—things that we have learned before, even as children. As we grow up, what are the risk factors for pain to become chronic? We need to understand that it is the combination of biological factors and all of these other factors that drives the chronicity, in one way or another.
The theme for this year at NAPS is “Biggest Neglected Problems in Pain Research and What to Do About Them.” What do you think those problems are? And what should we do about them?
For me, it really is the issue that I brought up: While we’re very good at treating acute pain, we are very bad at treating chronic pain, and we need to understand the mechanisms that drive the chronicity. Basic and clinical science have to come together in a better and more collaborative way. IASP has always been excellent in attracting researchers from the basic sciences and bringing them together with clinical scientists such as myself. This was something apparent early on with John Bonica, when he formed IASP. He felt that pain is such a complex condition that we need to bring basic and clinical scientists together, along with other health care providers, so that we can find the best management for pain.
But if you ask me what we can do about treating pain, I think there will never be a specific treatment or wonder pill that will cure it—it’s too complex for that. What we need to work on is prevention.
What type of work have you done advocating for policy change or health services?
I was heavily involved with IASP, having been on the IASP Council for many years and serving as president of the organization from 2005 to 2008. In that sense, I did quite a lot of work in this area. This included activities in developing countries in Southeast Asia, where I have been responsible for bringing IASP chapters together, and also starting new pain chapters. For example, I started the chapter in Myanmar. I’ve been invited several times to Myanmar by the government to focus on pain and what we can do about it.
What are some of your proudest moments as a pain researcher?
One of the best moments was when I completed my thesis. The opponent for my thesis was, in fact, Patrick Wall, who came and examined me, and he had some very nice remarks to me that I have kept. He is one of my heroes in pain and pain research, and I’ve been scientifically close to him and communicated with him after my thesis; I talked to him several times. He was one of the most excellent people I’ve ever met, and he was also responsible for some of my first studies on amputees and phantom pain in which we documented that pain itself is a risk factor for the development of chronic phantom pain later on. It’s interesting that a basic scientist like Wall had such insightful thoughts about clinical phenomena.
Another person who influenced me was William Livingston, who was a clinical and basic scientist in Portland, Oregon. He started one of the first pain clinics. His mantra was that “good clinical science starts with clinical observation.” I have kept this mantra as my own.
It’s also been wonderful to see all the PhD students we have educated. Several of them are now leading consultants and professors. For example, one of my former students, Nanna Finnerup, who is a wonderful person and a gifted scientist, is now the head of the pain research center at Aarhus University. So the next generation is safe, and this is wonderful to see.
Is there anything you’d like to say about where the field of pain research should place its efforts, moving forward?
It is great to see a new generation of researchers and health care providers getting involved in pain research and management. It is important to note that pain is the most common condition that brings a patient to the doctor, so we need to understand and recognize pain in order to assess and treat it properly.
At the beginning of NAPS, there was an icebreaker exercise where the faculty and executive committee made three statements, two of which were lies, and one of which was true, and then the trainees had to guess which statement was true. When it was your turn, we saw a photo of you with Princess Diana. What was it like to meet her?
Well, I will pose a question to you: Do you think the photo is real or not? Do you think it’s Princess Diana or it’s not Princess Diana?
The plot thickens.
Well, unfortunately, it’s not really Princess Diana. It was a photo taken at the IASP World Congress on Pain in San Diego in 2002. The local arrangement committee had invited actors and students to walk around dressed up as important and famous people, and this girl acted as Princess Diana. We had a long talk and a drink.
Kyle Vader is a PhD student in rehabilitation science at Queen’s University, Kingston, Canada.