Young Investigator Spotlight on Hadas Nahman-Averbuch: A Lifespan Approach to Preventing Migraine

By Neil Andrews

Hadas Nahman-Averbuch, PhD, is an assistant professor of anesthesiology at Washington University School of Medicine in St. Louis, US. She obtained an MSc and a PhD from the Technion-Israel Institute of Technology in Haifa. While in Haifa, she worked with Professor David Yarnitsky at the Laboratory of Clinical Neurophysiology, specializing in pain modulation mechanisms in adults with chronic pain. She completed her postdoctoral fellowship at Cincinnati Children’s Hospital Medical Center in Ohio, US, with Professor Robert Coghill. During her fellowship, she focused on neuroimaging techniques to examine neural changes in pediatric patients with chronic pain and in response to interventions such as cognitive-behavioral therapy.

Dr. Nahman-Averbuch opened her lab in 2021, with a focus on the impact of sex hormones on chronic pain conditions like migraine. In this interview, she speaks with Neil Andrews, a science journalist and Executive Editor of the Migraine Science Collaborative, to discuss her work, what it's like to launch a new lab, and her advice for young investigators. The interview has been edited for clarity and length.

What is the overall goal of your research?

I want to learn how sex hormones impact the prevalence and intensity of pain, and I’m taking a lifespan approach to do that. Specifically, I'm looking for a better understanding of the changes that are happening during puberty, including changes in sex hormones. That fits perfectly with migraine, because puberty is the time when there are significant changes in migraine prevalence; some adolescents have more symptoms starting around that time.

But you can take this even further to other periods in life with significant changes in sex hormones, such as older women who are in menopause or women who are pregnant. There are many times in one’s life when sex hormones are changing and can impact pain. I was very surprised to see how little work there is about this.

How are you studying this, and what are you most interested in learning?

I’m interested in so many things about this! First, we really don’t know, even with healthy adolescents without chronic pain, how the pain system and pain sensitivity change during pubertal maturation. Most of the studies show a reduction in pain sensitivity, but we don’t know how this happens – what is driving it? I think it is hormonal changes that will cause this reduction in pain sensitivity, but is it driven by changes in testosterone? If so, is it through an effect on the brain? Are psychological parameters important? We also don’t know what is happening during pubertal maturation in adolescents with chronic pain, including migraine. Do they still show the reduction in pain sensitivity?

One of our studies will focus on healthy individuals, and I’m trying to make sure I choose participants who are not likely to develop chronic pain symptoms as they mature. A second study is looking at healthy adolescents who are at higher risk of developing chronic pain. A third study will look at adolescents with pre-existing chronic pain and see, as they mature, if they have changes in their chronic pain severity or response to experimental pain. Migraine is the main condition we will be investigating in these studies.

What do you hope to know 10 years from now that we don't currently know?

My hope is that we will know who is going to be diagnosed with chronic pain, during or after puberty, and that we will be able to implement interventions that will delay this or reduce the pain intensity, or even completely prevent chronic pain from emerging.

What we do now in the field is treat pain after it has already occurred. But if we know someone is at high risk – say, for instance, there is someone who has a good chance of having migraine as they go through puberty – then let’s do something in advance and lower that risk. Preventing chronic pain will be the Holy Grail.

Do you anticipate that preventive treatments that could be developed for migraine and other painful conditions will be psychological treatments, pharmacological treatments, or everything under the sun?

My plan is to conduct a clinical trial that will come after my current study, and my first choice is going to be psychological or behavioral interventions. This is because we know these interventions help adolescents who already have migraine, so maybe these approaches can help them before they develop migraine. This will have fewer side effects than biological treatments. I don’t know how feasible it will be to give preventive medications to adolescents who don’t have migraine yet, but the behavioral ones will definitely be feasible.

If we are talking about sex hormone levels, there are medications that impact them, such as oral contraceptive pills or opioids. So maybe for adolescents at high risk, perhaps changing their hormonal status a bit will protect them during this critical time.

But the main consideration will be feasibility: things that have fewer side effects, that people have access to, and that they may try anyway.

Some of your previous research has looked at the effects of cognitive behavioral therapy (CBT) on migraine. Will this continue to be a focus of your work?

Yes – CBT is going to be my first choice for a behavioral intervention to prevent migraine onset.

Switching gears, your lab website states that the lab “includes a multidisciplinary team and fosters collaborations between physicians, psychologists, physiotherapists, and basic scientists to better understand chronic pain mechanisms.” Why are these multidisciplinary and collaborative aspects so important?

As much as I want to say that I know everything – and when I was young, maybe I thought that I did! – I now acknowledge that I don’t. Each topic is so complicated, and I won't be able to do good research without collaborating with other experts.

When you go to the clinic, it’s very different than in the research world, and we need to acknowledge this. The bottom line is to help patients, to make sure that their lives are getting better, and so researchers need to be connected with clinicians.

However, it is not always easy to link researchers with clinicians; it can actually be very challenging. For example, when I go to headache conferences, the majority of attendees are clinicians. When I talk with people or go to dinner with them, I am with people I didn't know before and they are talking about things I don’t know about, such as medications and patients – life in the clinic. It's very different from what I know, and it’s very difficult to talk with someone who you don’t have shared experience with; it's difficult to contribute to that conversation. And then the things that I talk about are probably foreign to them.

So, as a researcher, I tend to attend more pain conferences. When I go to a pain conference, that’s my tribe. People understand what I’m saying, more or less, and I understand what they’re saying. We are talking in the same language, and I can have a conversation with them. There are clinicians there, but not as many.

It is not optimal, but this is the current situation and we need to change it and make sure there are more discussions between researchers and clinicians.

You opened your lab just last year. What was that like?

It was very different from everything I had ever experienced! No one really prepares you for it. I compare it to opening a small business: You do the marketing, you are a mini-HR, you’re managing people, you're managing the budget – you’re like the accountant. You’re doing so many things, and while I know the science, I don’t know all those other things.

It’s exciting that you finally get to do your own research, and starting my own lab is what I was dreaming about, but it gets very busy, very quickly. Everything that you thought is going to take a month takes six months. It’s a very exciting and interesting experience, but it's also scary: All of a sudden, it’s all up to you.

Are there things that are particularly challenging or surprising?

What is challenging is how to make sure that I’m choosing the right people for the lab. This was especially true during COVID, when you don’t see people in person and everything is done over Zoom. Making sure that I’m a good mentor is also challenging. I hope I am, but I wish I received more training about this.

What advice do you have for early-career people?

They need to know that in our field of work, there’s so much rejection. But it’s really not about them; a lot of times it’s just being in the right place at the right time.

I would recommend to people that they network. Networking is helpful and it’s never too early to start. Start talking with people and let them know if you’re looking for a postdoc or a faculty position. You want to be on people’s radar.

Also, I know it’s difficult during COVID or even during regular times to just go talk to someone or send them an email. But most people are very nice; they’re not intimidating. It’s okay, even as a PhD student, to send an email to a professor. I’m surprised sometimes that people don’t realize that. But it really is okay: Yes, you can just send an email and say, “Hi, I love your research. Do you have time to talk?” The worst-case scenario is that they will say no or will not respond. But again, most people are very nice and willing to help.

I think that younger folks in particular have a hard time asking for help.

I used to be so shy; I probably did not speak for the first six months when I started my master’s degree. And now I don’t stop talking!

A lot of people have imposter syndrome – it is real, and it is okay to feel this way. I want early-career people to know that other people, too, are not sure about themselves, even if they don’t show it. So, don’t feel bad about yourself. I think it's especially important for early-career people to know this.

There’s been more attention recently on gender issues in science, particularly in helping women advance in their field and navigate their careers. What are your thoughts about that?

I have kids, and I was really lucky to have mentors who acknowledged and accepted that; if one of my kids was sick, I was able to stay at home with them. So, having a supportive mentor is one thing you need to consider when you are searching for a PhD or a postdoc. I have a supportive husband as well, who was willing to move with me to the United States.

I am also very involved with professional societies. Being a woman could actually be a benefit in some societies because there are not a lot of women represented at these societies and they want to add diversity. So, if you want something, volunteer. The worst-case scenario is that you will not be selected.

However, it is important to remember that it can be a double-edged sword, because your time is the most precious resource that you have, so it’s also okay to say no to things. You need to be aware of how much work you’re taking on.

You also need time with your family – that’s not something that you need to apologize for. You can take vacation days and just disconnect, because otherwise it will impact your work.

Now, I know I’m saying this, but I’m not good at it; I can be on the beach and be thinking about work! But I know I need to get better at this – acknowledging it is half the battle.

This interview was originally posted on Migraine Science Collaborative.

Neil Andrews is a science journalist and Executive Editor of the Migraine Science Collaborative.