Editor’s note: The second North American Pain School (NAPS) took place June 25-29, 2017, 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 “Where Does It Hurt and Why: Peripheral and Central Contributions to Pain Throughout the Body.” 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. This is the third installment of interviews from the Correspondents, whose work is featured on PRF and RELIEF, PRF’s sister site for the general public. See the first, second, fourth, and fifth installments of NAPS interviews.
Martin Schmelz, MD, is a professor in the Department of Anesthesiology at the University of Heidelberg in Germany. His current work focuses on the translatability of electrophysiological work in animal models and experimental pain paradigms in humans to persistent pain in patients. Schmelz sat down at NAPS with PRF-NAPS Correspondent Harriet Kemp, a clinical research fellow at Imperial College London, UK, to discuss collaborative research, mentorship, and translational pitfalls. Below is an edited transcript of their conversation.
How did you become interested in pain research?
It was completely by chance. I had wanted to become a cardiologist or a neurologist, but when I graduated from medical school I found a job in occupational medicine. From the outside that might seem really boring, but it was actually very interesting. While I was in that job, a clinical research center was starting at the University of Erlangen, and it was looking for postdoctoral applicants for a collaborative project on pain. I loved physiology and thought, “Why not apply?” So that was the start, and I stayed with this group because the atmosphere and spirit were so great.
During this year’s NAPS there has been a lot of talk about mentorship. Throughout your career, which mentors have you learned from or have shaped your research?
There are two main aspects to mentorship. First, what can I learn from how a mentor teaches? Two mentors who inspired me are Hermann Handwerker and Peter Reeh in Erlangen—working with them was a unique situation. They switched back and forth between disciplines, had open discussions with different groups without making false distinctions based on the types of experimental method each group used, and tried to strengthen collaborations wherever possible. They were not particularly picky about things like authorship; they just wanted to move the research forward.
Second, they loved what they were doing, and that is what kept me in the field of pain research. They would always focus on content and important scientific questions rather than get stuck worrying about personalities and politics. So they were not mentors in the traditional sense of the word, in terms of directing your career, but you learned from their approach to research. They gave postdocs free rein to explore their ideas and try new directions, which showed that they trusted you.
You do a lot of translational work. How applicable are the experiments pain researchers do in animals and in healthy people to the human pain experience?
The approaches we have in animals and in human volunteers are valuable for understanding certain aspects of pain. However, what we currently observe in clinical work is too dominated by ideas coming from the experimental field. Think about some of the key questions in pain—for example, the transition from acute to chronic pain, spontaneous pain and supra-threshold pain. Then look at the models and the terminology that we use—these are all based on threshold responses such as heat and mechanical pain withdrawal thresholds. These are very different things.
This is probably because it is so hard to come up with different behavioral measures in animals. It’s complex—the animal won’t talk to you! But the patients do, so it is a strange situation: We accept these threshold limitations in patients rather than playing to the strength that humans have in differentiating among stimulus intensities. So a lot of the translation that we currently pursue is actually going in the wrong direction. It would be much better to play to the strength of the species in which we do our investigations.
What is holding researchers back from doing this?
It is very problematic to devise new models—it takes time, and there is always the pressure to publish. If you use a known measure such as quantitative sensory testing (QST), you know you can get published, and that helps your career impact factor-wise. But does this really help move the field forward? We need to take some time to have an overall vision and direction that may be different than the status quo. We must constantly ask, Is this experiment really taking us in the right direction, and is this solving a question that is clinically relevant?
But you do see it sometimes, don’t you? Someone has a completely novel idea, and it takes the whole field in a new direction?
Yes, but there is always the intermediate phase where no one believes or listens, and the researcher is told all the time why he or she is wrong. You need lots of accumulated evidence and data to convince people, but that can take five or 10 years. It is often a battle between the old and new generation of researchers.
Earlier you mentioned collaborative research. What are the benefits of this approach?
Your motivation is much higher, and when you invite people into your laboratory as guests, you are more likely to be strict with yourself and stick to the plan. Standards are also better because you have to be open to input from others. You also have discussions that act as an internal check: What are the limitations of our work? What should we change? What is really good? Collaboration really does the work of the journal referees, and this is particularly important for trainees. If your collaboration has clinicians and basic scientists, both sides help to keep the work in perspective and to improve your concepts.
Is there any downside to collaboration?
If you are very open with your ideas, of course the downside is that the ideas might spread without your name attached to them. Sometimes you win, sometimes you lose, but overall it will always be a win, as it is more fun. You need to like coming to work in the morning and like the people who are there. If you don’t, you probably are not in the right environment. If I were forced to be secluded and secretive in what I was doing, I would hate it because the fun comes from the exchange of new results and ideas, and the feedback that others give you to guide your research. If the alternative to sometimes seeing your ideas pursued by others is to work alone, I definitely think that would be worse.
How do you deal with tricky aspects of collaborations such as authorship?
It really depends on the personality and situation. Sometimes you have a PhD student who desperately needs first authorship. As I see it, within a group you are all working on slightly different aspects of the research, and therefore you can distribute first authorship more easily; often you can negotiate across several papers so an individual does not lose out. Students need to understand that they also win by freely sharing their data so that they can contribute to a better paper rather than just doing everything on their own. As you become more senior it is your role to act as the moderator.
You also mentioned before that one of the big questions in pain research is the transition from acute to chronic pain. How are we doing on this problem?
We have a feeling that treating acute pain might prevent the transition to chronic pain. This may or may not be true, but there aren’t many clinical studies on this aspect. I assume it is because this type of research is very involved—it requires time and money, but it is crucial. We do cross-sectional studies to understand this issue, since these are easier to do, but what we need are prospective studies.
As an anesthetist, I am very concerned about what I can do to treat acute pain in order to prevent chronic postsurgical pain in my patients. Anesthetists are taught that this transition can partly be due to central sensitization and that if we limit acute painful input, this will reduce the risk of persistent pain. Is there enough evidence that central sensitization even exists in humans?
In the strictest sense, central sensitization means an increased response at the spinal level to the same electrophysiological input, and I don’t think there is any doubt that this exists. But whether this is required for the development of ongoing pain is another question. For example, a patient may or may not have punctate hyperalgesia or brush-evoked allodynia but may still develop ongoing pain.
During the talks at NAPS we were discussing a newer concept: the ability of the central nervous system to judge how important a pattern of input is, which involves a learning process. This learning involves both strengthening descending inhibitory control and potentially increasing noxious input through nociceptive sensitization in the central nervous system. It is these learning processes, which we haven’t figured out yet, that are crucial for the transition from acute to chronic pain, and which could be a target for treatment.
Additional Reading
Helås T, Sagafos D, Kleggetveit IP, Quiding H, Jönsson B, Segerdahl M, Zhang Z, Salter H, Schmelz M, Jørum E
Eur J Pain. 2017 Sep; 21(8):1316-25.
Namer B, Ørstavik K, Schmidt R, Kleggetveit IP, Weidner C, Mørk C, Kvernebo MS, Kvernebo K, Salter H, Carr TH, Segerdahl M, Quiding H, Waxman SG, Handwerker HO, Torebjörk HE, JørumE, Schmelz M
Pain. 2015 Sep; 156(9):1637-46.
Itch and pain differences and commonalities.
Schmelz M
Handb Exp Pharmacol. 2015; 227:285-301.
Inflammation meets sensitization - an explanation for spontaneous nociceptor activity?
Rukwied R, Weinkauf B, Main M, Obreja O, Schmelz M
Pain. 2013 Dec; 154(12):2707-14.
High spontaneous activity of C-nociceptors in painful polyneuropathy.
Kleggetveit I P, Namer B, Schmidt R, Helås T, Rückel M, Orstavik K, Schmelz M, Jørum E
Pain. 2012 Oct; 153(10):2040-7.
Obreja O, Ringkamp M, Turnquist B, Hirth M, Forsch E, Rukwied R, Petersen M, Schmelz M
Pain. 2011 Sep; 152(9):2138-46.
