Editor's Note: Three young investigators were honored with awards at the International Association for the Study of Pain’s 16th World Congress on Pain in Yokohama, Japan, 26-30 September 2016. After the meeting, the award winners spoke by phone with Neil Andrews, PRF executive editor, to discuss their research. Below is an edited transcript of an interview with Luana Colloca, winner of the Patrick D. Wall Young Investigator Award for Basic Science. Interviews with the two other award winners will appear soon on PRF. Also see interviews with Marco Loggia and Tasha Stanton.
Luana Colloca, MD, PhD, is an associate professor at the University of Maryland School of Nursing, and School of Medicine, in Baltimore, US, where she leads a lab focused on placebo analgesia and nocebo hyperalgesia. Colloca earned an MD from the University of Catanzaro Medical School, Italy, in 2002; a PhD in neuroscience from the University of Turin Medical School, Italy, in 2007; and an MA in bioethics from the University of Turin in 2008.
Why did you become a pain researcher?
I started my PhD in neuroscience with a project on Parkinson’s disease, working with Fabrizio Benedetti at the University of Turin in Italy. This was quite an interesting line of research, which looked at changes at the level of single neurons after a pharmacological intervention, such as the anti-Parkinson’s drug apomorphine; we did this research in surgical patients (Benedetti et al., 2004). During this time, I became very interested in placebo effects, but the research was very slow to address the questions I was interested in, since we had only about two patients per month, and there were also many ethical restraints in working with patients with severe Parkinson’s disease.
I wondered what the best way was to address my questions about placebo effects, and I decided that it was by studying pain, for two reasons. First, you can investigate pain in a laboratory setting. Second, studying pain appealed to me as a physician because it is common across so many different diseases and patient populations. I also thought that what I learned about placebo could eventually be translated to help patients with pain.
What is the focus of your lab?
My lab examines behavioral and neural mechanisms of placebo analgesia and nocebo hyperalgesia in healthy volunteers and in patients with chronic pain. We are also investigating the genetics of pain as well as demographic factors, including sex, race, and age, and how those factors affect pain modulation.
Some of the issues we are interested in understanding are the differences between placebo responders and placebo non-responders; the extent to which placebo analgesia is a protective factor against pain; and if the ability to activate the descending pain modulation system is a predictor for the response to pain killers, as well as for lesser severity of pain.
In what ways do you hope to translate your research to the clinic?
We have two perspectives on this. First, we want to exploit placebo effects in patients to improve pain management. Placebo analgesia is a model to target the descending pain modulation system, and we aim to discover how to encourage the release of endogenous substances to reduce pain―both its intensity and its affective components―to improve descending modulation of pain in people.
Second, from the perspective of clinical trials, placebo effects are a huge problem. The proportion of pain trials that fail because of placebo responses is extremely high, so there is a need to improve clinical trial research methodology in order to minimize the placebo effect. At first, people were skeptical about this, but now there is interest in educating patients and physicians about placebo effects before starting a clinical trial, in carefully measuring patient expectations, and in strategies to reduce the placebo effect as much as we can. It's possible that this will eventually result in new designs for clinical trials.
What is the most exciting finding from your lab so far?
People have believed that placebo analgesia is primarily linked to opioid, cannabinoid, and dopamine signaling. But we recently found, for the first time, evidence that arginine vasopressin given intranasally can enhance placebo analgesia (Colloca et al., 2016). We were also able to show a sexually dimorphic effect, where this enhancement of placebo analgesia occurred only in women and not in men. These findings come from a clinical trial where we compared healthy people receiving intranasal vasopressin to those receiving intranasal oxytocin as a positive control, intranasal saline, or no treatment.
For future research, my goal is to go back to the vasopressin system and learn more about how vasopressin can modulate not just placebo analgesia but also pain at a neural level. There isn't too much in the literature on this topic, and it is fascinating that there is a dimorphic hormonal influence.
What is the most surprising finding from your lab to date?
One of the most surprising things is that we can learn to develop placebo analgesia just by observing other people (Colloca and Benedetti, 2009). When I started doing research in this area, the main theory was that placebo analgesia was related either to expectation or to subconscious conditioning. But I was always a little bit skeptical that this was the whole story.
What we showed was that perceiving analgesia in another person, without any direct experience about the interventions the other person was going to receive, produced a robust placebo response comparable to that from prior experience with a conditioning procedure. So we can modulate pain merely by social observational learning. This was surprising because it challenged the current framework for placebo analgesia (Colloca and Miller, 2011), which emphasizes psychological mechanisms, but we showed there is a social component, too.
What are the key questions in the field of placebo analgesia, and where do you think the field will be a decade from now?
The main question in our field is to understand why there is such large variability in placebo analgesic responses across healthy individuals and across patients. Henry Beecher, who started this line of research in 1955, worked to understand this question, but today we have more tools and knowledge to address it. Over the next 10 years, by combining genetic and brain imaging approaches, we will be able to target, more and more, the neurobiological mechanisms underlying placebo analgesia and understand why some people respond and others do not.
Another interesting aspect for the future is to understand how the modulation of pain induced by expectation, by conditioning, and by learning is integrated across systems, such as the opioid, dopamine, and vasopressin systems.
Clinically, I have hope that we can actually harness placebo mechanisms to help patients cope with pain. Placebo analgesia can be thought of as a kind of inner healing system, and we don't really take advantage of it. The goal will be to develop strategies to harness placebo analgesia in real-world settings by empowering our expectations, for instance, or by improving the doctor-patient relationship. Placebo analgesia is really an example of the complexity of pain modulation and the necessity of a multidisciplinary approach to pain management.
What is the biggest challenge facing young scientists?
Science is quite competitive, and so one of the challenges is to identify an area of research where you can contribute with passion, creativity, and novelty. When you have this kind of attitude and motivation, other challenges, like finding a position or a grant, are easier to face.
If you could have dinner with one scientist, living or dead, in the pain field or outside of the pain field, who would it be and why?
I would love to have dinner with Eric Kandel. When I started my medical degree and was studying neurophysiology, I decided to read his book [Principles of Neural Science] to learn more about brain physiology. It was inspiring, and I decided eventually to do a PhD in neuroscience once I finished my medical degree. At the end of my PhD, I actually met Kandel in person, but I was too young to fully appreciate meeting him. Now that I am wiser than before in science, I would appreciate it more.
When you're not doing science, what are you doing? Any hobbies?
I love music. For example, I regularly attend the Baltimore Symphony Orchestra to listen to classical and contemporary music. I also like to volunteer.
Is there anything else you’d like to mention that we haven’t discussed?
Considering the influence that Kandel’s book had on me, I think we should introduce, in any basic book on neuroscience, a chapter on placebo analgesia/descending pain modulation for PhD students in neuroscience. This is something that doesn’t get covered in graduate programs, and I think it's a real need. We are learning a lot about placebo analgesia and brain modulatory systems, and it's time to consider this with the seriousness that other big topics in neuroscience receive.
