Senior manager’s note: PRF is thrilled to announce that Rebecca Seal, PhD, has agreed to serve as PRF’s new editor-in-chief. Dr. Seal is a professor in the departments of Neurobiology and Otolaryngology, and the Pittsburgh Center for Pain Research, at the University of Pittsburgh School of Medicine, US. She received her PhD training at the Vollum Institute, Oregon Health and Sciences University, Portland, US, and her postdoctoral training in the departments of Neurology and Physiology at the University of California, San Francisco, US. Her laboratory, which investigates spinal pain circuits and develops novel therapeutics, has openings for new graduate students and postdocs. You can contact Dr. Seal for further information via Twitter – @lab_seal.
Having served as a member of the PRF Editorial Board for several years, Dr. Seal is uniquely equipped to serve as its editor-in-chief. Rebecca spoke with Lincoln Tracy, a research fellow and freelance writer from Melbourne, Australia, about her path to pain research, her involvement with PRF to date, and what she hopes to achieve during her time as editor-in-chief. Below is an edited transcript of their conversation.
What was your path to pain research?
I started studying pain as a postdoc at UCSF [University of California, San Francisco]. My project was focused on a transporter – VGLUT3 – that packages glutamate into synaptic vesicles. I wanted to know what role this transporter had in the nervous system because when it was discovered, it was somewhat of a surprise. Two other transporters together were thought to account for all of the vesicular glutamate release in the mammalian nervous system, and many of the cells that expressed VGLUT3 were not known to release glutamate as a transmitter. So there was some controversy about what this transporter might actually do. When I knocked it out in mice, they were profoundly deaf. To our delight, we discovered that inner hair cells of the cochlea rely on it for vesicular glutamate signaling of sound information to downstream neurons. This set the stage for my studies to examine how VGLUT3 contributes to glutamate neurotransmission throughout the mammalian nervous system.
At one point, I had the idea – based on a paper by Peggy Mason at University of Chicago, US – that the transporter could have a role related to pain at the level of the brainstem, but our laboratory did not study pain. So we reached out to Allan Basbaum, whose laboratory was just across the courtyard at UCSF. He kindly listened to my idea and then asked his postdoc Xidao Wang if he would like to help us investigate the possibility. Indeed, though not related to the brainstem, we found that the VGLUT3 knockout mice develop little to no injury-induced mechanical allodynia [seen when touch becomes painful after injury; see related PRF interview from 2013]. From this experience, I became enthralled with studying pain and all that remains for the field to discover about the manifestations of persistent pain and how we can better treat it.
What is the aim of your research?
My laboratory continues to focus on understanding the neural circuitry and mechanisms underlying mechanical allodynia. When I started my lab, we determined that VGLUT3 has a role in the spinal cord circuitry for mechanical allodynia, and I was excited to go on this journey into the cellular organization of the dorsal horn and its role in persistent pain. Since that time, we and others in the field have developed a new framework for the dorsal horn circuitry for mechanical allodynia. The work points to the existence of a complex network that is differentially activated depending on the nature of the injury. We are really interested in carefully dissecting the neurons that are involved and the different mechanisms for how this circuitry is activated by various kinds of injury. Non-opioid-based therapeutic strategies derived from these studies are also in development.
We are also actively developing tools to study primates and just completed a study to characterize the neuronal organization of the dorsal horn across species from rodent to primate. For therapeutic efforts, we compare what we learn from interrogating circuits in mice and what our colleagues see in humans to try and synthesize the available information – what are the similarities and what are the differences? By doing this, we hope people can use our findings to translate their work more efficiently from rodents to humans. There isn’t a lot of primate research going on, and there are a lot of challenges – cost, availability, additional space requirements, etc. However, optimizing critical new pain therapies like the targeted gene therapies we are developing requires using models other than mice.
Your research goes beyond just pain, as seen in your work looking at glutamate signaling in cochlear neurons. What can different areas of the nervous system teach us about pain?
I think it’s helpful to understand how different sensory systems work, as they can teach us a lot about pain and somatosensation. We can learn a lot about how different sensory systems integrate with one another, which happens throughout the brain. My interest in looking at pain and the auditory system started when I learned about people with hearing loss. These individuals experience tinnitus, or a ringing in the ears, but can also suffer from hyperacusis, where they become overly sensitive to sounds. It gets to the point where they perceive normal sounds to be unbearable and agonizing.
Now, this hasn’t really been described as pain per se, but having met people with this condition, I’ve seen how unpleasant it is and how it really affects their lives. It makes me wonder about injury-induced hypersensitivity in the somatosensory system – is there something conceptually similar going on in the auditory system of these individuals?
Is there something within your area of research that we don’t currently know, but hope we will know in the next 5-10 years?
Well, we don’t really know a lot about the circuitry and connectivity between the periphery and the central nervous system. I think this is somewhere we will make a lot of progress over the next five years. We also don’t have many good non-opioid therapeutics. As I said earlier, I think one of the most fundamental things that will help pain treatment is having a systematic understanding of the dynamics of neural circuits when you are injured, and of the nature of the injury, and the relationship between the two – both in mice and humans. The more we can understand this, the better the therapeutics we will be able to develop.
How did you first get involved with PRF and join the Editorial Board?
Although I knew about PRF – which is such a gem for our field – and I was a huge fan of Neil [Andrews, former PRF executive editor], I didn’t know a lot about the Editorial Board and exactly what they were doing. I was nevertheless excited and obviously honored to be invited to participate as the Board was – and is – made up of scientists I really admire. Ted Price, who is so passionate and energetic, was an amazing editor-in-chief of the Editorial Board.
What are you hoping to achieve during your time as editor-in-chief?
One goal I have is to increasingly integrate Editorial Board members in the development of new content and other aspects of PRF. The Pain Beat podcast came when the Editorial Board was discussing content and Petra [Schweinhardt, Balgrist University Hospital, Zurich, Switzerland] suggested that PRF do a podcast. That sounded exciting to me, so I approached Neil and Ted after the meeting to let them know that I thought it was a fantastic idea and would be excited to be involved. Things took off from there.
The point of The Pain Beat, which is on Spotify and Apple Podcasts in addition to PRF, was to capture casual conversations that happen amongst pain experts, as what might happen over drinks in a bar at a conference. It is often one of the more fruitful ways that scientists can share ideas, thoughts, and theories that lead to new projects and collaborations. I thought it would be nice to capture conversations like these. Often in panel discussions at conferences, people aren’t willing to really go “out on a limb.” That’s exactly what we want on the podcast – to hear what people think and then debate it if there are differing opinions among the guests. During the pandemic, we held them over Zoom. I’m looking forward to being back at in-person meetings, holding them there, and continuing to create episodes over Zoom.
The other thing I would really like to do is facilitate increased communication between different organizations involved with the Editorial Board, like the IASP Chapters and the Rita Allen Foundation. I’d love to see PRF functioning as a truly global hub for pain researchers to get to know each other’s work.
Honestly, it is my goal to carry on the phenomenal job that Neil and Ted did. Neil gave so much to PRF, and nurtured it from the early days to the point where thousands of pain researchers absolutely love it – it’s such a great concept and platform, and, as far as I know, unique to the pain field. I really appreciate all their efforts and will strive to embody the high standards they set. I am enjoying working with Greg Carbonetti, the new senior manager of PRF, who is also fantastic. He has lots of energy, passion, excitement, and is open to new ideas to keep PRF growing and thriving.
What do you do when you’re not doing research – any interesting hobbies or secret talents?
I’ve adopted a couple of dogs recently, and we’ve been having a lot of fun spending time together. One is a boxer/coonhound mix and one is an Australian blue heeler. They’ve brought a lot of joy to my life. As you probably know, Lincoln, the blue heeler listens really well, but never sits still. Anyway, it’s been great to get out and take them on long walks.
Lincoln Tracy is a researcher and freelance writer from Melbourne, Australia. You can follow him on Twitter – @lincolntracy.