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North American Pain School 2019: A Conversation With Visiting Faculty Member Cheryl Stucky


9 October 2019


PRF Interviews

CherylStucky

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 Andy Tay, a postdoctoral scholar, Stanford University, Stanford, US, interviewed visiting faculty member Cheryl Stucky, PhD. Stucky is the Marvin Wagner Endowed Chair at the Medical College of Wisconsin (MCW), Milwaukee, US. She is also director of the Neuroscience Doctoral Program and director of the Pain Division of the Neuroscience Research Center at MCW. Her lab studies the molecular, cellular, and physiological mechanisms of sensation, particularly how we sense touch and pain. She is interested in how our skin cells communicate with sensory neurons to convey touch and cold, the causes of severe pain in sickle cell disease, migraine pain, and the causes of neuropathic and inflammatory pain.

 

Here, Stucky talks about her path to pain research, her work on the TRPA1 ion channel, science communications, and diversity in science. Below is an edited transcript of the conversation.

 

How did you become interested in science?

 

I grew up in Kansas on a farm, so I spent a lot of time outdoors with animals, and I was always fascinated with flowers, trees, and biology.

 

My mom was a medical technician in a hospital and ran the technical aspects of the hospital and the clinic, and she would let me work with her to help with her assays—and I was only eight years old when I did that! So she would give me blood samples on slides, and I could do blood counts underneath the microscope. I would also put together the EKG traces for the patients’ charts for the doctors. She would say to me to never, ever let the doctors know that I was doing this for her. She also paid me to wash out tubes of blood—and I was doing it with my bare hands because we didn’t know anything about bloodborne pathogens at that time! It was a very memorable experience.

 

How did you become interested in pain research?

 

I decided to enter a graduate school program in neuroscience because I had an opportunity as an undergraduate to study norepinephrine receptors in rats. For that study, I had to get rats from the pet store. It was crazy! I bought around 12 rats, and I put them in a bucket to take them with me. The woman who sold me these rats was very suspicious!

 

I later went to the University of Minnesota’s neuroscience graduate program and had a few lab rotations. I was undecided which lab to join, but my PhD advisor, who was in pain research, told me that if I went to her lab, we would publish the paper that I had worked on during my rotation with her, and she would make me the first author.

 

So it was an accident that I went into pain research but also the best decision. This is because pain was, and still is, a fairly small field. You can carve out your own niche. It’s also a very translatable type of work, which is really attractive to MD and PhD students. It’s a place where you can make an impact. At least I sure hope so!

 

What do you think are the three biggest questions in pain research?

 

The first is, How are we going to get targets from animal models and, using our genetic assays, decide which targets are the best to take into the clinic? We have been talking about this throughout NAPS, and I still think that is one of the biggest questions out there.

 

The second question is, Why is pain so different in different people? Why do people who appear to have the same or similar injury or disease experience pain in such dissimilar ways? Why do some patients with a pain disorder respond to a drug and others do not? This gets into personalized medicine and how different genetic factors affect pain.

 

Then, the third question is about the influence of epigenetics. It’s fascinating that the experiences you and I have had in our lifetime could change our genome and could change genetic expression in our kids. Are these protective factors against pain, or are they pain-promoting factors? Do they give us resilience or susceptibility? And how can we sort that out?

 

In your work, you found that the ion channel TRPA1 plays a role in pain. Can you say more about it?

 

TRPA1 is affectionately known as the wasabi receptor. When you eat wasabi with sushi, the perception of that hotness, which goes up your nose and straight to your brain, comes from the activation of TRPA1. TRPA1 is a receptor that can be activated by a number of things—by a lot of different exogenous factors in the environment.

 

But TRPA1 can also be activated by things your body makes, like hydrogen peroxide and lipids. And so, what we and others have shown is that the TRPA1 channel seems to serve as an amplifier in sensory neurons. That is, although TRPA1 is not directly involved in how a neuron responds to a mechanical stimulus, once you have an injury, especially one that involves inflammation, it’s the booster signal. If you can block that signal by blocking TRPA1, you can ease pain hypersensitivity, but leave tactile information and acute pain detection intact.

 

How can we synthesize all the information we have about the roles of different ion channels, receptors, and molecules involved in pain?

 

You’re getting at such a good question. We all know that a given sensory neuron doesn’t only express TRPA1—maybe it also expresses TRPV1, certain sodium channels, and other types of channels. How do we deal with multiple channels on a single neuron? What’s the most important thing?

 

It gets even more complicated, though, because when you have a painful stimulus on your skin, for example, you’re not just activating a single neuron, but a population of neurons that have overlapping receptive fields. So you’re dealing with spatial summation and multiple types of afferent fibers. There are also inhibitory neurons that are dampening down the signal at multiple different levels of the CNS.

 

It really depends on what ultimately gets encoded in the signal through each level, from the periphery to the spinal cord and up to the brain, and how that signal gets through. In the end, though, I would say that if a therapy can, let’s say, peripherally block 30 percent of the signal across a summated amount of afferent firing, then potentially that’s therapeutic.

 

Still, it amazes me that a given compound against a certain target can have such a marked effect on its own—I just have a hard time getting my head around that one. How is it that when I block TRPA1 in the skin, or in the primary afferents, this has such a marked effect on pain behavior?

 

Chronic pain affects so many people, and I personally know people who have lost faith in the pace of treatment development. As a pain researcher, how do you communicate the field’s progress so that people with pain can be hopeful?

 

We need to talk more about our successes but also show that we are very aware that we need to do more and think harder, considering that pain is such a complex problem. It is also important that patients understand that there is hope, but we don’t want to overextend our findings to the point where we are sensationalizing them.

 

It’s about striking the right balance of saying, “This is exciting, it is an advance, it has potential, but there’s still a lot to do to ensure that it’s effective, safe, and will work in many people.” Also, you’re talking about taking very complex issues—issues that are complex for pain researchers themselves—and trying to explain them all in a way that makes sense to the public.

 

I really believe in communicating to the public. I am a Mayday Fellow, and part of my goal is to engage the public and talk about pain research and the advances we are making. I regularly give talks to Kiwanis Clubs, Rotary Clubs, and other community groups, and I would like to broaden this impact beyond Milwaukee, Wisconsin, because it is so important, and I enjoy doing it.

 

There is a lot of conversation right now about diversity in science. How do you think we can better train underrepresented groups in STEM (science, technology, engineering, and mathematics)?

 

First of all, you have to open your mind to having underrepresented students. For example, you need to have high school and undergraduate programs to bring people in and get them excited about science. Next, you have to keep them in your pipeline to develop not only their skills but also their self-confidence. Self-confidence is not to be underestimated when it comes to any trainee, but certainly for those who come from underrepresented groups, that is one really important thing. Because I had low self-confidence as a child, I understand it well and am probably more sensitive to this when I see it in trainees. I really enjoy having a diverse lab, including members of the LGBT community, and I believe that they find my lab welcoming and inclusive. Finally, it’s important to get them out to give talks, network, and highlight their work.

 

The academic job market is highly competitive now. Do you have any advice for those who want to become faculty members?

 

For those that are interested in an academic position, I strongly recommend doing an academic postdoc. I also strongly recommend publishing, but I do not think you have to publish “major-level” papers. You just need a good number of solid papers where you are the first author and the main driver. Overall, you want to be productive, well rounded, and know your project, your science, and your area as well as possible, so you can really nail all those questions you will be asked to find out if you were the driver on a paper. It also helps a lot to hone your communication skills and to know how to professionally engage with others. The job talk should never be underestimated. It is critical to give an outstanding job talk, and that is something you have a lot of control over. You need to convey that your project is yours and that you own it.

 

Interested to know more about Stucky’s research? Take a look at her lab website.

 

Andy Tay is a postdoctoral scholar at Stanford University, Stanford, US.

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