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 Marco Loggia, winner of the 2016 IASP Ulf Lindblom Young Investigator Award for Clinical Science. Also see interviews with Luana Colloca and Tasha Stanton.
Marco Loggia is an assistant professor of radiology at Harvard Medical School, Boston, US; associate director of the Center for Integrative Pain NeuroImaging (CIPNI); and a faculty member at the MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, US. He received a PhD in neurological sciences from McGill University, Montreal, Canada, in 2008.
Why did you become a pain researcher?
As an undergraduate student at Vita-Salute San Raffaele University in Milan, I fell in love with the study of neuroscience. I knew I wanted to pursue a graduate degree in it, hopefully abroad, and within a field with potential clinical impact—that was something important to me. So when the time came to choose graduate schools, I rapidly zeroed in on McGill University. McGill was—and still is today—a world-class institution with a great and historic neuroscience program. McGill also happened to have the additional appeal of being located in Montreal, which is an incredibly multicultural, vibrant, and fun city; this was definitely an important aspect for a 20-something-year-old.
I quickly discovered that McGill was home to one of the most important pain research centers in the world, now called the Alan Edwards Centre for Research on Pain. I didn’t know much about pain, but it did fit the bill as a neuroscience topic that could have clinical impact, and it sounded like a very interesting field. I ended up applying for a position in the lab of Catherine Bushnell, the center's first director and also a pioneer in the field of pain neuroimaging. To my delight, I was accepted into the lab.
What does your lab focus on?
My lab studies how the human central nervous system—mostly the brain but recently the spinal cord as well—processes and is affected by pain. We focus on the nervous system because it is increasingly obvious that this is where many changes take place during chronic pain. We study humans—in large part chronic pain patients—because I would like the gap between discoveries made in my lab and their clinical impact to be as small as possible.
What are the major projects you are working on now?
Most of my lab's work right now is focused on evaluating the role of neuroinflammation in human chronic pain. In the preclinical literature, there are many wonderful studies showing that glial cells, such as microglia and astrocytes, have an important role in the establishment and/or maintenance of persistent pain. If you block glial activation, pain behavior in animals can be prevented or reversed. But, while we know how to minimize pain in rodents, we don’t do that as well in humans, and the evidence linking glia to human pain is weak. Demonstrating that glial cells have a role in human pain, as they do in animal models, would open many new avenues for diagnosis and treatment of chronic pain.
To address this issue, we are using brain imaging in chronic pain patients, using a radioligand that binds to proteins expressed in active glia. So we are able to visualize glial activation in vivo, which is something that is pretty exciting. Early attempts to use inhibition of glia as a means to achieve pain relief have not been successful in people so far, and the question is, Why? What we’re suggesting is that by performing glial imaging studies, we might be able to identify patients that may benefit the most from glial modulation as a treatment approach.
What is the most exciting finding from your lab so far?
Last year, in 2015, we published in the journal Brain the article that I consider my most important contribution to the field so far [see PRF related news story]. In this study we used integrated positron emission tomography/magnetic resonance imaging (PET/MRI) to show that patients suffering from chronic low back pain show significant elevation in brain levels of a translocator protein that is a marker of glial activation. These results are exciting because they suggest that glial cells may indeed have an important role in chronic pain in humans, as predicted by many fantastic animal studies, and therefore may be viable therapeutic targets for pain.
What is the most surprising finding from your lab to date?
In our study in Brain, we were very surprised by the consistency with which the patients demonstrated elevation in the glial activation signal. Typically, brain imaging data are a bit noisy, so you need to do a lot of averaging across multiple subjects to find a signal of interest. In our study, the signal elevation was so consistent that just by looking at individual-level data you could tell who the patients with chronic back pain were and who the controls were. This is very rare in human imaging studies.
Another surprising thing I learned from my studies, more generally, is how committed chronic pain patients are to research. They really go to great lengths to help out even when they know that they may not experience any direct benefits from the study they’re participating in. I’m really grateful for their commitment.
What future projects do you have planned?
We are now focused on gaining a better understanding of the significance of our initial observations and potential implications arising from them. For example, do all chronic pain conditions show neuroinflammation? Do they all show similar patterns, or are there disease-specific glial signatures? Can neuroinflammation predict the transition to chronic pain? Can we modulate neuroinflammation pharmacologically or otherwise, and if so, does that affect patients? An important prerequisite to the exploration of all these questions will be, first of all, to replicate our original findings. While exploring something new is usually seen as more exciting (and, ultimately, more "fundable"), assessing the replicability of our original observations is extremely important to me.
Where do you see the field of brain imaging in the next 10 years?
These are really exciting times for the field of brain imaging, because it’s undergoing a process of critical introspection as we speak, which is aimed at strengthening its scientific rigor. There is a big range in the quality of brain imaging studies out there, and I think this is going to change. Undoubtedly, this will increase the impact that brain imaging can produce.
In addition to "rigor," another key concept in the next 10 years will probably be "integration." This means combining multiple imaging modalities, including PET, MRI, electroencephalography, transcranial magnetic stimulation, and others. It also means integrating brain imaging with other disciplines, such as genetics, immunology, and others.
What is the biggest challenge facing young scientists?
One of the biggest challenges is finding the means to support the establishment of one’s own niche. When young scientists want to make the leap from being a trainee to finding an independent position, it can be quite difficult to convince study sections and grant review committees that they can do something quite different from what they learned in their mentor’s lab. This is a problem because it limits the rate of innovation that can be achieved from one generation of scientists to the next. It also limits the cross-fertilization that occurs when someone from a different discipline enters a field. If, for instance, someone from an immunology background wanted to get into brain imaging, that person would bring fresh ideas that could really propel the field. By allowing themselves to be more risk tolerant, funding agencies may make a huge difference.
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 the legendary Brenda Milner. When I was at McGill, she was actually part of my advisory committee, but I did not have the opportunity to have a chat with her much besides annual committee meetings. When I was doing my PhD, she was already in her late 80s, yet she was going to the lab every day and often surprised me with her sharp mind and acumen; she was pretty incredible. I still have a copy of my PhD thesis proposal with her handwritten edits, which I keep as a very treasured item.
I would choose her because she’s had an incredible career spanning more than six decades, and has made major contributions to the field of cognitive neuroscience. Dr. Milner was the first person to study “H.M.” [Henry Molaison], the most famous patient in cognitive neuroscience. She has also worked with historical figures such as Donald Hebb, who was her PhD advisor, and the neurosurgeon Wilder Penfield (famous for his somatosensory and motor "homunculi" that are in every neuroscience textbook). She would have so many interesting anecdotes.
When you are not doing science, what are you doing? Any hobbies?
I have played piano and keyboard in many bands throughout my life. For instance, I played keyboard in a rhythm and blues band, and was a pianist in a gospel choir. I was also the keyboard player in two different Pink Floyd tribute bands, and when I was in Montreal, I played in jazz combos at the McGill Conservatory. I’ve also done some studio recording. But all this happened before three little people came into my life—my kids. So as of late, I mostly play the soundtrack from the cartoons they watch, but I’ll be back onstage again in the near future. Stay tuned….