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Michael Pasternak, Ph.D., is a Founding Trustee of the Facial Pain Research Foundation. Dr. Pasternak spoke with Mervyn Rothstein, who was an editor and writer at The New York Times for 30 years. Mr. Rothstein now writes the "Stage Directions” column for His first symptoms of trigeminal neuralgia occurred in 2005. 




Mervyn Rothstein and Michael Pasternak


MR: Michael, much has happened since our last interview, more than three years ago. What’s the status of the search for a cure for Trigeminal Neuralgia and related neuropathic pain? How many scientists are seeking a cure, in how many cities and countries? What are the ways your medical researchers are seeking answers, and how are they doing so? Please talk about the nine ongoing research projects to find the cure.


Our research is making great progress. Our first-ever research studies are the biggest leap toward finding the causes and lasting cures for Trigeminal Neuralgia in the last 1,000 years. But it’s complicated. Very complicated. Because in the old days, nine years ago, when we got started – January 9, 2011, when we had our first meeting, we hadn’t even started the research, the trustees came together and we made the goal to find the cure – it was all based on the belief that compression on the trigeminal nerve was the only reason for all Trigeminal Neuralgia. 

But as we began to develop projects, and do the research, we discovered that there are other reasons as well. We know that trigeminal pain can also be caused by the myelin that sheathes the nerves being unhealthy and damaged. We know that there can be mutated genes responsible, genes that are not functioning properly, that are not protecting the nervous system. We also know that the nerves themselves can be damaged, in one way or another, by surgery or for other reasons. So we had to undertake research in all those areas.

For that reason, we have 18 lead investigators working in the United States, Canada, Israel and the United Kingdom. Numerous locations. And in each location, we also have technical assistants, post-doctoral researchers, many, many people working on our nine different projects to find the cures. 

For example, to deal with the damaged nerves, we reached out to Allan Basbaum at the University of California, San Francisco, who had done work on using neuro-stem cells to fix damaged nerves in other areas of the body. And we asked him to apply his work to the trigeminal nerve. That research is ongoing, and is making progress. 

To cite another example, for our work on causal, damaged or mutated genes and DNA, we needed 1,000 DNA samples from people with Trigeminal Neuralgia from nine collection centers in the U.S., Canada and the U.K.  And we needed to make sure that the people providing the samples really had TN and not some other related disease. And we succeeded.

No other rare-disease research has ever collected that number of samples in a process that assured excellent phenotyping – screening for the disease. And now we want to look at their DNA, we want to know where the mutant genes are, what the sufferers’ genes have in common.  when you ask what’s the status, the answer has to be very complicated. But the status is that in each of our projects, we have made progress, and we continue to make progress. We now know, for example, where in the brain the pain is occurring. We know the pathway of the pain from the trigeminal nerve to the brain stem to the place in the brain where the pain is experienced. And now that we know this, we’re working on how to block the pain pathway – block the pain from getting to the pain centers. 

So the answers, and the cures, are going to be different for different people. Some will need to have their myelin repaired. For example, in our research for the last eight years at the University of Florida, we know that in tested animals there are ways to repair the myelin that can put a stop to the pain. And now, as in most of our projects, we are beginning to talk about human studies. 

MR: When the Foundation was started, you set a goal of finding a cure by the end of 2020. That’s now. How do things stand?

That’s a good question. We will soon formally announce that this year, we will be initiating our first two human treatment studies. In scientific timelines, that’s pretty amazing. Because you must remember that over the last 50 years, the treatments for Trigeminal Neuralgia have hardly changed. The same anti-seizure drugs, the same pain relievers, the same surgeries – very little has changed in that regard.  And rates of cure using the old treatments have been really disappointing – in over 50 percent of microvascular decompression surgeries, the pain returns in 10 to 12 years, according to the National Institutes of Health. And the NIH says that the other, less invasive, surgeries have to be repeated in one to three years. They also recognized that in many pain patients the surgeries and the medications aren’t working.

This year we will have our first two human studies. And we feel terrific about that. (The people for the studies will be chosen by the scientific researchers, not by the Foundation.) And in each of our other projects, we can see on the horizon, and are preparing for it, that we will be able to move toward the trials.  The Foundation has raised the necessary funds to pay for this research and the goals are becoming closer every day to being achievable.

Now some of these curative treatments may work for some and not for others, because there are those different causes. That is why we have to create different cures – to repair the myelin, to repair the nerves, to block the ability of the nervous system to send those pain signals to the brain. But we feel great about our progress during these nine years, and we’ll keep going until everyone has the opportunity to stop the pain.

MR: The Foundation is an all-volunteer organization. There are no paid employees. The volunteers handle communications, fund-raising, and all other functions. I volunteer my time because I know first-hand, as someone who has experienced and suffered from the excruciating pain of Trigeminal Neuralgia, how important it is to find a cure. How did you get the thousands of other volunteers to sign up?

I think we did an incredible job of speaking to the public. Remember when we got started, because of this disease, the suffering and the treatment, there were billions of dollars being lost annually in productivity and medical costs. And more important, and more humanly unaffordable, was how dearly the unfortunate people suffering from this disease paid in quality of life – their health and longevity and stability and dignity and independence, their careers and family roles, their relationships and social ties, their physical abilities, their shattered sense of hope, of meaning or purpose. Many of these people were totally disabled and many were reaching out and saying they’d rather be dead.

We had a very sad situation. Great strides had been made in curing other diseases or creating better treatments for them, but with Trigeminal Neuralgia nothing new had been achieved for more than 50 years. There were the same treatments for TN that had existed for a half century. So when we reached out with our communications to tell people that we wanted to create cures, and that we wouldn’t stop until we found the answers, we were readily and strongly embraced.

I think a part of it was that we expressed the commitment to be an all-volunteer organization – that nobody was going to make money off of this. That almost all of the money we collected – close to 98 percent – would go to the research projects.

And I believe that this was very meaningful to the scientists as well. Many of their institutions dropped overhead costs for us, knowing that we were a nonprofit organization paying for this research. So we saved money in that way too. And I believe that it was the right time and the right place for a group of us who had been working hard to assist people with this terrible pain, and the public appreciated what we were doing, and they joined us.

In addition, I think that 90 percent of our volunteers are sufferers or family and friends of sufferers. They are people who have first-hand knowledge of the terrible toll of this disease, and they are contributing, they are developing fund-raising events and other activities. They are an important part of this Foundation.  Without our volunteers we would not be able to fund the research to find the cures. 

MR: Is it still true that 95 to 98 percent of the donations go directly to the research projects. And how is this possible?

It’s absolutely still true. We have no employees. I think if you add up the amounts of money that we save as a result, it’s far beyond the money that we spend on the research.  Imagine hiring someone like you to do these articles for the Foundation, for the web newspaper. You’re not cheap, Merv. You’ve made a pretty good salary doing what you do. Just multiply that to all the little things that are done by all the volunteers – like a former college professor and a school principal who spend hours every week sending out thank you letters that are required by the I.R.S. for the donations. Imagine the volunteers who are meeting with the scientists on a regular basis, paying for their own travel costs to Canada or the U.K. or the East or West Coasts. When you start adding up the amounts of money that we are saving because of volunteers, it’s simply amazing what we’ve created.

MR: In the Foundation’s nine years of existence, how much money has it received in donations? How much more do you think you will need?

Cash coming in may have been $7 million, but the real number is closer to $45 million. Because we also have a program where we approach other foundations that give the money directly to our scientists – they prefer sending the money to the universities, for example. In many instances, people are giving in kind or matching money. Even the stamps we use for our envelopes are donated. It’s been very successful.

And another example is our Facebook page, which has been wonderful for getting donations. They can be $1 or $5 or $10 or $100 or $1,000, and they are anonymous. And much appreciated.

How much more will we need? That’s a great question. Much more, especially once you get to the human trials. For our first trial, much of it will be paid for by the National Institutes of Health, which is the first time something like this has occurred. But for the second trial, we’ll need probably another $3 million.

As an example, take Neurona, the company that was formed by Allan Basbaum out of U.C.S.F. for the neuro-stem research. Neurona raised close to $50 million to be able to take those neuro-stem cells and develop them, and they have 34 full-time scientists working on this project. Neurona has three directions they’re going – one is research on epilepsy, one is back pain and the third is Trigeminal Neuralgia and related neuropathic pain. They need those cells tested on animals by the very best testing service. We’re going to pay, at one of our centers, $370,000 to test those stem cells – which we believe are going to stop the pain and fix those nerves – on the animals.

When that is completed, Neurona is committed to putting at least millions into the Food and Drug Administration and clinical-trial approval process. We won’t have to pay for that. Neurona’s goal is to take the cures to the market.  This one example of how our FPRF scientific consortium can work.  In this case, the University of Florida, Neurona and us. This is  the first time there are three distinct organizations pulling together to get a research job done.  Neurona developed the cells, UF tested the cells and the Facial Pain Research Foundation covered the testing costs.  And how that happened was simply a matter of bringing those scientists together at our International Consortium of Scientists, which we hold at least every other year. And the the scientists work together on their projects. How that happened was simply a matter of the FPRF functioning in a leadership role to say how can we get this done. And it just made sense to do it this way.  And it’s not how things normally happen in scientific research.

MR: Both you and I have suffered from Trigeminal Neuralgia, and we both have been lucky. You, and other sufferers, have had a surgical procedure that has eliminated the excruciating pain. Others, like me, take medication that has been effective in keeping the pain at bay most of the time. But, as you’ve noted, the surgery and the medication don’t work for everyone, and often don’t last forever, and for the many others less fortunate, severe pain has been part of their daily existence. In truth, Trigeminal Neuralgia can be a fatal disease. It has historically been known as the suicide disease, and both you and I know of people who have so sadly decided they can no longer live with the horrible pain.  What can you say to those who still suffer? Why isn’t the research moving faster? And what can be done to accelerate the pace? Will there be a cure?

The first thing I would say to them is that I’m sorry we didn’t start earlier. We relied too long on the medical community to create better answers and better treatments. And I can say to them to have hope. To believe that a cure can really be found. If you look at our scientists, you’ll see this is something meaningful. They are outstanding in their fields. Take a look at our work and you can see that progress is being made and that you need to have hope and that there are great people working on this problem. And we’re going to get the job done. We’re committed to doing it and we believe it can be done.

It’s going to take more money. It’s going to take a great deal of money. But no scientist has said no to us, and we have been able to raise funds all along, not dependent on federal money, because we can’t wait for federal money. That system works for some, but it’s very bureaucratic. And we can’t wait for the government to pay for this research. We need it tomorrow because people are suffering.  We invite everyone to join us on this incredible journey to find the cures.



Mervyn Rothstein interviews 

Orion P. Keifer, Jr., M.D., Ph.D.


Mervyn Rothstein Interviews

Cory R. Nicholas Ph.D.



Cory R. Nicholas, Ph.D., is a co-founder and chief scientific officer of Neurona Therapeutics. He is also an adjunct assistant professor at the University of California, San Francisco. Before co-founding Neurona, Dr. Nicholas was a faculty member in the Department of Neurology at the University of California, San Francisco, where his research program was focused on investigating the development of human cortical interneurons from their earliest stages to maturity.

Dr. Nicholas pioneered methods to obtain interneuron forerunners from human immature stem cells that were capable of being transplanted into multiple animal models of neurological disease. Neurona was conceived in 2008 to investigate the potential of neuronal cell-based therapy – using such cells as a basis for eliminating neurological pain. Dr. Nicholas and his co-founders, John Rubenstein, M.D., Ph.D., and Arturo Alvarez-Buylla, Ph.D., were among the first to do research that led to the discovery that these cells could potentially inhibit hyper-excitable neural networks in relevant neurological disorders – that the injected interneuron precursor cells became integrated into neural circuitry, possibly allowing for stable repair of the injured nervous system.

The Facial Pain Research Foundation recently agreed to finance a cooperative research project between Neurona and the University of Florida’s McKnight Brain Institute to test the Neurona neuro-stem cells to see if they will stop neuropathic pain in animals. The study should take from 12 to 24 months. If it is successful, Neurona plans to seek Food and Drug Administration approval to begin studies in humans that hopefully will lead to clinical use. 

Dr. Nicholas spoke by telephone from California with Mervyn Rothstein, who was an editor and writer at The New York Times for nearly 30 years before retiring in 2010. Mr. Rothstein has also written for Playbill Magazine, and now, since 1991. He currently writes the Stage Directions column for the Playbill web site. He was diagnosed with Trigeminal Neuralgia in 2005. Dr. Nicholas spoke about his research, Neurona, the agreement with the Facial Pain Foundation, and his future hopes.

Why did you decide to focus on pain in your career?

I’m a developmental biologist and I was studying the development of the nervous system, specifically the development of inhibitory nerve cells that are the basis of the collaborative work with the foundation. And we had a colleague at the University of California at San Francisco, Allan Basbaum, who was very interested in seeing if these inhibitory cells could be applied to the treatment of pain, which is his expertise. So our groups joined forces. We were able to work together, and Allan in his laboratory took this and really pioneered application of the cellular transplants that we were studying in the brain and applied them to the spinal cord. And he was able to show that the transplantation of those cells could ameliorate and in some cases completely reverse the experimental pain sensitivities in rodent models of neuropathic pain. 

What is the importance of this Trigeminal Neuralgia research study?

I think this is a tremendous opportunity to take the next step and to build upon the work from Allan and others in our group and really to leverage the resources from the network at the Facial Pain Research Foundation. Because we’ve not yet tried putting these human nerve cells that we think can be restorative and potentially curative into any type of animal model of Trigeminal Neuralgia. One of the reasons we weren’t able to do this on our own is that we didn’t have access to the animal models of this disease. These animal models are quite nuanced and can be difficult to establish on our own. That was when we were introduced by Michael Pasternak of the Foundation to John Neubert at the University of Florida, who had this model. He’s been studying it for a while and had it up and running at his lab. Thankfully Michael Pasternak and the Foundation were able to make that introduction.

How would you describe the work being done at Neurona and its future and its progress?

We submitted a proposal to the Foundation that was just funded where we can do three things. Number one, we can see if the pain phenotype – the observable pain characteristics –  that John has studied for a long time in his animal model can be extended to an animal that does not have an immune system. We need an animal that does not have a functioning immune system to allow for the long-term persistence of the human cells in a rat, because the same kind of immunosuppressants that we will be using in the future, potentially in clinical trial for humans, those drugs don’t always work in rodents. So we had to change the animal strain – so that is the first aim, to see if we can produce a stable pain phenotype using the animal model of Trigeminal Neuralgia that John has studied.

The second aim to see whether our human interneuron cells could be delivered using neurosurgical stereotaxis – a method of locating points within the brain – specifically into the regions where we think the pain triggers are in this disease, and to see if those cells will persist with long-term stability in those rodents.

And then finally, if we succeed with the first two, to see whether the human cells can demonstrate disease-modifying activity and significant compelling pain reduction in this rodent model. If we satisfy all those conditions, then I think we really have considerable support and rationale to pursue a clinical trial in humans for treatment of drug-resistant, intractable Trigeminal Neuralgia. And of course we then have to work with the Food and Drug Administration to run a battery of safety and toxicology studies before doing the first trial. But those would be the next steps.

When do you envision (or hope) that cell-replacement treatments for neuropathic pain (including Trigeminal Neuralgia) will be tested on humans and eventually be ready for use in humans?

The first study, with John, is between one and two years long. And then it would probably be another two to three years of working with the F.D.A. to set up the clinical trial.

What are the biggest obstacles that you face in translating your preclinical findings to the clinic?

That’s a really good question. It’s one that is common not just to pain but just about to any disease, especially in the neurological disease space. And that’s quite simply because rodents are quite different from humans in many aspects. There are different anatomies, different neural circuitries. And especially with pain, where you don’t know how an animal such as a rodent is feeling. We use instead, in lieu of an actual communication as to how a rodent is perceiving pain, we use surrogate experiments to measure aversive behavior or hypersensitivities, in terms of how the animals are moving their limbs or responding to a stimulus. Those surrogates are of course never the same thing as asking a person if they’re experiencing pain. So it’s both the anatomy and the ability to be able to communicate.

On top of this, there are many confounding aspects of pain – psychological, emotional – as well as a very high placebo effect. Which makes all of this very difficult to translate from rodents into humans.

The Facial Pain Research Foundation is moving forward with a sense of urgency to find cures for Trigeminal Neuralgia and related neuropathic pain.  Why have you linked your efforts to such a new organization is the field of pain research?

We were looking for ways to apply this stem-cell technology. First of all, pain was an important potential indication for this kind of cellular transplant. But when we heard from the Foundation the stories of people who are suffering with this disease, it really pulls at your heartstrings and you want to do whatever you can to help.

It just seems like pain is an indication that really does possibly lend itself to testing this proposed cellular therapy. Because it’s a disorder that’s focal in nature – there’s a focus of pain in the facial region that can be targeted, so we have a target to deliver the cells, which is one of the criteria we have for applying the cellular therapy. Because the cells are delivered directly into a lesioned area. They’re not delivered systemically. So when we think about diseases that we can address with this technology we think about a disease that has a well-described focus – an area such as the trigeminal ganglion or other aspects near the brain stem where we think the pain trigger exists in Trigeminal Neuralgia.

This is still quite controversial in the field and nobody knows for sure. So because we don’t understand the cause, it gets back to your question about what makes it difficult to translate to humans. That’s another important aspect as to why this is a tough bridge – because we don’t really know yet what causes this disease. Which is true for many diseases. So we do our best to recapitulate using artificial triggers in rodent models.

Every day many people are contacting the Facial Pain Research Foundation asking if it is truly possible to find a cure for Trigeminal Neuralgia. How would you respond to their questions?

Absolutely I think it’s possible. And I think the Foundation is funding some tremendous work. The Foundation has wisely spent its dollars on leading-edge research to understand the causes of the disease, looking very carefully at human genetics. And complementing this basic understanding with attempts at a cure using gene therapies, and cell therapies like ours. So I think there have been very rationally thought-out efforts to try to cure the disease with the technologies we have and the information we have, along with efforts to understand the causes of the disease.

What keeps you awake at night?

It’s always how do we continue to fund this important research so that we can truly try to make a difference and help people who are suffering from this terrible disease. There are just not enough research dollars available from the National Institutes of Health. There are very few means to acquire dollars for cutting edge moon-shot types of ideas. I think this was a perfect opportunity for the Foundation to connect a couple of different research efforts, one on animal models and the other on stem cell technology, with one another to give  it a shot and see if we can see some efficacy in these animal models. And then if we do, the next step will be trying to figure out how to garner the dollars for the next step, to march this toward the first clinical trial in humans. That’s where it gets very difficult, because the dollar amounts go up. But I think the Foundation has really done a terrific job in seeding these efforts to take that important first step. And if we can determine that this can potentially represent a very effective, long-lasting therapy, possibly a cure, then there’ll be more evidence and rationale and support and enthusiasm for this to snowball. But we’re going to need all the stakeholders to come together on this and continue to raise the dollars to keep this going. And that’s always a source of anxiety – how do we get the dollars to investigate the feasibility part of this, which is what we’re talking about with this first project. But then once we demonstrate feasibility, how do we sustain that, to make this a real human-therapy clinical trial for patients who are suffering. That’s the two-fold anxiety that keeps me up. 

Mervyn Rothstein Interviews

 Dr. Wolfgang Liedtke


Wolfgang Liedtke, M.D., Ph. D., is a professor in the Departments of Neurology, Anesthesiology and Neurobiology at Duke University in Durham, North Carolina. He is an attending physician in the Neurology Clinics for Headache and Trigeminal Sensory Disorders and an attending physician in the Innovative Pain Therapy Clinics of the Department of Anesthesiology at Duke. Both as a physician and as a scientist, his focus is on understanding mechanisms critical for pain and inflammation in order to alleviate suffering of patients afflicted by therapy-refractory pain – pain that does not respond to treatment – with the emphasis on trigeminally-mediated pain (trigeminal nerve pain, also head-neck pain), but also other nerve and joint pain. As an attending physician, he has encountered more than 1,500 cases of refractory trigeminal pain disorders, as well as chronic migraines.

The Facial Pain Research Foundation has provided a grant to Dr. Liedtke and the Duke University Center for Translational Neuroscience as one of the Foundation’s projects to find cures for trigeminal neuralgia and related neuropathic pain.  Dr. Liedtke and his group at Duke are exploring how material science and material science combined with cellular engineering can be used to make transmission of neural signals in the trigeminal system normal again.

Mervyn Rothstein, who was an editor and writer at The New York Times for 30 years, now writes the "Stage Directions" column for, and is a former member of the Tony Awards Nominating Committee. His first symptoms of trigeminal neuralgia occurred in 2005.

Dr. Liedtke spoke with Mervyn Rothstein.


WF: As a junior trainee, I was exposed to pain because of the places where I trained, in Zurich, Switzerland, and in Germany. Programs there were run by expert and master physicians, and I was impressed by how they were able to help patients suffering from chronic pain. And I was also profoundly touched and moved in a very basic human level by the suffering that I saw, and that I could not fail to notice. Seeing how the physicians treated and diagnosed these patients impressed me, and I volunteered to help them from my junior perspective and work with them and do the first interview of the patient. I saw that I could do this pretty well. I have a good feel for it and can communicate well with patients who suffer from chronic pain.

When I shifted more toward basic science in a laboratory setting, I happened to make a discovery that was important and relevant to pain, which was sort of serendipitous because I was aiming much deeper and looking for basic new mechanisms. It turned out that the TRPV4 ion channel, the signaling molecule, which I discovered two decades ago, is a relevant, significant player in pain, also craniofacial pain. We found it expressed in the trigeminal ganglion in small neurons, which meant this could be relevant to pain.

Then, moving to Duke University, for my first independent faculty position, with the lure of being both a physician and a scientist, I decided that pain would be a very appropriate theme for me because it would allow me to practice pain medicine and also move forward my pain-related discovery in the basic science research lab.


I’m extremely grateful for the support of the Facial Pain Research Foundation because it enables me to take a project that is at the drawing board stage and has some initial data to it and give it a more solid base under its developing legs.

On the drawing board the imagination was to harness the power of stem cells that we engineer to become a certain type of cell that will help to function as an anti-pain generator and get that specifically engineered cell close to a key anatomical site of the trigeminal system, the cisternal trigeminal nerve root, which is the target of the well-known microvascular decompression operation and is also the target for the gamma knife radiation procedure [two medical methods of eliminating or alleviating trigeminal neuralgia pain]. Rather than operating or radiating we propose to bring cells close to the nerve root and engineering the cells so that they function anti-pain, so that they secrete and produce natural anti-pain modulators. By forcing them to reside close to the trigeminal nerve root, they will calm down and bring down the excitation level and inflammation level in the nerve root and in the entire trigeminal system.

And in positioning these cells right next to the cisternal trigeminal nerve root we will use a material that functions as a holding device. The cell-holding device we will also accomplish what the traditional, good old-fashioned microvascular decompression accomplishes, which is to protect this critical part of the trigeminal system against mechanical injury.

In a parallel approach, while we move forward with “encaged” cells, we will also try to take advantage of a new nanomaterial [material made up of building blocks that are at the nanoscale] that I have done work on previously through my collaborative network here at Duke University, where we have material scientists and chemists and we harness the novel advantageous properties of a model carbon nanomaterial to use as a shield/ wrapping material for the trigeminal system. It could be described as facilitating a neuro-protective environment.

These are the two approaches I’ve articulated and for which I’ve received support from the Facial Pain Research Foundation and which might have significant implications for other types of pain. These approaches could be applied to other nerves that were injured, resulting in nerve pain, for example a lumbar root of the sciatic nerve, the cervical nerve roots that supply the arm or other peripheral nerves (sciatic, ulnar, median). Both methods are translatable to these other types of neural injuries.


The conception of these ideas is based on the thoughts and fantasy and imagination one has but also on new theories or other findings that are sprouting up within the field, what you read and what you hear at conference meetings. Microvascular decompression works in a number of patients, not in all, and it has other issues involving it, so I was certainly not the only one thinking about trying to upgrade or make it more contemporary, more focused. What I’m proposing is based on relatively recent findings that I hope to take advantage of. So these ideas weren’t possible before these new findings were made public.


I strongly and profoundly believe that transformative steps can be taken to deal with this form of pain. It depends on the definition of cure. There is the possibility of a so-called miracle cure, where something is done and the patient is totally cured – the pain is out of the life of the patient who was tormented by trigeminal neuralgia. But the miracle cure is harder to accomplish than a decent and what I call a transformative level of pain control, whereby pain is reduced to a level where patients can lead a normal life again, can participate in life and deal with the remaining amount of pain disturbance that the disease still poses. I believe that is something we can accomplish through implementing and translating research for more and more patients.


We live in exciting times.  We have so many tools at our fingertips. If only we had the money. That is one obstacle – availability of funding to realize our ideas – not just bold ideas that lead to brave new experimental approaches on the laboratory bench but also something is translatable, and is equally daring or has a decent chance of leading to dramatic advances.

Also there are administrative and so-called red tape obstacles that would not cost a lot of money to overcome - rewriting or redoing the complex rules that govern the scientific research game and especially the rules governing translation into new treatments that will be available to patients. Scientists and doctors can make their voices heard, but this is an involved national and international decision-making process where our views are of limited impact. I am enthusiastic that the Facial Pain Research Foundation is becoming partial to the ways of how to revisit and reform the process.                                           


I feel privileged and I’m very happy about this association. They are like-minded people. I intend to go after this disease. I attempt to accomplish this goal of transformative change of treatment effectiveness through novel engineered treatments. That is my mantra. And there is nothing hollow about it. Every single letter of that is true to the core of who I am as a professional.

So with that, I notice that the Facial Pain Research Foundation is managed and is driven by people with whom I have zero disagreement in that respect. I am so happy and so proud to be a part of it.

Editorial Note





Mervyn Rothstein

Mervyn Rothstein who was an editor and writer at The New York Times for 29 years. Mr. Rothstein now writes the monthly "Regional  Theatre" column for Playbill Magazine and is a former member of the Tony Awards Nominating Committee. His first symptoms of trigeminal neuralgia occurred in 2005.



John K. Neubert, D.D.S., Ph.D., is the principal investigator for the scientific research project entitled Mapping Towards a Cure: Identification of Neurophysiologic Signatures of Trigeminal Neuralgia Pain, at the Evelyn F. and William L. McKnight Brain Institute of the University of Florida. Dr. Neubert is a tenured associate professor in the Department of Orthodontics at the University of Florida College of Dentistry. He also has an adjunct appointment in the Department of Neuroscience at the University of Florida College of Medicine and is on the faculty of the McKnight Brain Institute. Dr. Neubert spoke by telephone from Florida with Mervyn Rothstein, who was an editor and writer at The New York Times for 29 years. Mr. Rothstein now writes the monthly “Regional Theatre” column for Playbill Magazine and is a voting member of the Drama Desk, an association of theater journalists. His first symptoms of trigeminal neuralgia occurred in 2005.


The Interview


MR: Why did you decide to focus on pain in your career?


That’s a good question. When you go through your dental-student career, you learn that pain is very much a part of the public perception of dentistry. That’s what people associate dentists with. As a dental student, I was fortunate enough to be able to do research with someone with studied facial pain and who saw facial pain patients. And I became interested in trying to find better ways of eliminating pain.


MR: Your research involves locating and imaging the signature centers in the brain for trigeminal pain, and the pathways to those centers. Once you do that, what happens next? What are the research steps that need to be taken to find the cure – to stop the pain – and how difficult is this process of moving from finding the cause to eliminating it?


The first step is the imaging part. We’re hoping that we can find a common signature center, where the pain starts, in the different patients that we’re scanning. We’re also doing a similar study in our animal models. We’re hoping also that there’s an overlap in what we see in trigeminal injury models in rats, and in what we see in humans. Once we can identify the signature center, that will be the target for possible future therapeutic treatments.


It’s a difficult process. The first problem is the relatively small number of patients who have trigeminal neuralgia. It’s a relatively rare disorder. So to get a sufficient number of subjects is the first challenge. And the next challenge is to see if there’s that overlap in brain activity in a signature center. The last difficulty comes in translating these results into therapies, and in getting those therapies approved. What’s helping us is that we are working in parallel on the basic side – our animal work – trying therapeutics, so once we are ready to move to the human side we will hopefully have things ready to go as far as therapeutics are concerned.


MR: What is the importance of this trigeminal neuralgia study and what potential is there for having an impact on the study of other diseases and possible cures?


We’re hopeful we can come up with new therapies, because it’s a disease that’s largely resistant to many treatments, and people even after surgery can still have horrible pain. As far as impacting other disorders, the mechanisms that occur in the face are very similar to mechanisms that occur elsewhere in the body, so we have a very clean model for studying pain.  


MR: How have you and your research colleagues attacked this problem from a new perspective?


The neural imaging aspect is one of the more novel parts. People have done imaging for a number of years, and they’ve gotten very good at it. We’re using it in the sense of a biological marker, and we’re hoping that this neural image may also serve as a diagnostic tool. It could help people diagnose trigeminal neuralgia versus some other disorder that’s causing the pain. Our project Co-Investigator, Mingzhou Ding, is reknowned for his imaging expertise.  I also work with a lot of very innovative investigators here at the University of Florida in terms of the therapeutic side of things. My collaborators on the project, Robert Caudle and Marcello Febo, have some novel therapeutics as far as targeting specific pain fibers. And we’re working with another investigator here, Todd Golde, who is an expert on viral delivery of pain therapeutics.


That’s the direction we’re going to take in terms of innovation, in what we think will be the best approach for treating trigeminal neuralgia. It’s basically a very safe virus that you can program to modify certain genes. You can have genes and proteins increase or decrease, depending on what you program into this vector.


The nice thing about these vectors is that it’s just an injection. People who have trigeminal neuralgia start out with some medication like Tegretol and if that doesn’t work they go to some kind of surgery and they may go to another surgery. So the idea of using one of these viral vectors would be to do the injection prior to having surgery, to see how it works, Because you could always do the surgery afterward. It makes sense to have this kind of therapy. I think people would prefer it if we could just inject something to end the pain.


MR: Why haven’t researchers completed this research years ago?


Two main reasons come up. It’s like a lot of things – technology and money. Advances in technology relating to computer power have really accelerated in the last five or ten years. Our imaging studies, as far as analyzing the data and narrowing the resolution of what we’re trying to locate, use very powerful magnets and computers.


It also really comes down to funding. Trigeminal neuralgia is a relatively rare disease, and there’s not a lot of emphasis on trying to get money to study this disorder. Pain is one of those disorders that’s not a disease. There’s a tremendous need to find new products, new pain therapies, but the situation doesn’t fit nicely in any of the National Institutes of Health categories as far as funding needs go.


MR: What are the biggest obstacles you face in translating your preclinical findings to the clinic?


Probably it’s just going to be dealing with the Food and Drug Administration’s regulatory process as far as getting a new therapeutic treatment approved. That process can take many years. So if we’re thinking about injecting a viral vector or using some kind of other therapeutic, a lot of other studies have to be completed first. Toxicology has to be worked out – we have to make sure it’s a safe approach. And then evaluate the therapeutic efficacy later. One of the problems we run into as researchers and trying to translate things is that many substances or therapeutics work very well in mice or rats, but we’ve seen previously that when you take the same substances and try them on humans, a lot of times they fail. That’s always an issue.  Something that works on a rat doesn’t always work on a person.


MR: Every day many people in pain are contacting the Facial Pain Research Foundation asking if it is truly possible to find a cure for trigeminal neuralgia. How would you respond to their question? 


I would say it is possible. We’re putting a lot of resources and a lot of brainpower into the problem and we’re hopeful that we can find something. This is a collective “we” I’m talking about – including the other investigators who are involved with the Facial Pain Research Foundation, the groups in Israel, Toronto, Portland, San Francisco, London, New Jersey, North Carolina and Florida. There are a lot of smart people working on this project to find a cure.



Volunteers Suffering from Trigeminal Neuralgia Needed for this Brain Imaging Study


 Enrolling eligible volunteers to participate in a research study about brain imaging:


To be eligible you must be:


-18-75 years old


-Suffer from Trigeminal Neuralgia…diagnosed with Trigeminal Neuralgia


-Prefer Classical TN (Type 1) and Atypical TN (Type 2)


-Average Pain in the moderate to severe range


-No additional major health problems


-Be able to go to Gainesville Florida and spend approximately 4 hours


-Fluent in English (written and spoken)




-Unable to complete a magnetic resonance imaging (MRI) scan due to implanted


or un-movable metal material in your body or severe claustrophobia.



For further information about volunteering for this study call or email:


Dr. John Neubert (352) 273-5687 or This email address is being protected from spambots. You need JavaScript enabled to view it.


This Study is directed by Dr. John Neubert, UF College of Dentistry, McKnight Brain Institute



Mervyn Rothstein


Douglas K. Anderson, Ph.D.

In 2018 Douglas K. Anderson was the recipient of the US Congressional Certificate of Recognition and The University of Florida McKnight Brain Institute established the Douglas K. Anderson Facial Pain Research Program to fund future research to find cures for TN and neuropathic pain.

Douglas K. Anderson, Ph.D., is eminent scholar professor and chair emeritus of the Department of Neuroscience at the University of Florida, College of Medicine, former director of the McKnight Brain Institute at the University of Florida. He is director of research and a trustee of the Facial Pain Research Foundation. He was interviewed by Mervyn Rothstein, who was a writer and editor at The New York Times for nearly 30 years and now writes the Stage Directions column – a series of interviews with theater directors – for His first symptoms of trigeminal neuralgia occurred in 2005

Why did you want to be a scientist, and how did you become one?

I had a cousin who was a physician, and he kept after me to go into medicine, saying we would go into practice together. So between my junior and senior year at the University of Texas I got a summer internship at MD Anderson Hospital in Houston, which is a world-class cancer hospital. I was there for about three months, and about a month into it I realized that if I had to make a living as a doctor I would starve to death, because it was difficult for me to work with sick people. I was dealing with pediatric cancer cases and I would go home and cry. But I had spent about half my time working in the research laboratory, and I loved the lab. So I went back to school and changed my major from zoology pre-med to straight zoology. I didn’t tell my parents until Christmas – which was an interesting Christmas. And I went back to Anderson Hospital after I graduated and worked with a Ph.D. instead of an M.D. I got my masters at the University of Houston, and my Ph.D. at Michigan State in 1972.

You worked for 33 years for the Veterans Administration. What kind of work did you do?

I was there from 1973 until I retired in 2006. The V.A. was very good about allowing us to have appointments at medical schools, so I had a dual appointment. I was working on spinal cord injury both with my academic appointments and at the V.A. I was for a year the Department of Veterans Affairs Deputy Director of Medical Research.  

Why after more than 30 years of researching spinal cord injury did you decide to turn your efforts to finding a cure for trigeminal neuralgia?

The main reason was that spinal cord injury was so complex, because the spinal cord is so complex. We were working on locomotor function – movement – which is an incredibly difficult thing to do. Spinal cord injury is a constellation of symptoms – bladder function, sexual function, pain, temperature regulation, so many things. So I decided that instead of trying to hit a home run, I would go after a bunt single. One of the major complaints most spinal cord patients have is pain, and all scientists generally in a situation like that look for the simplest model. I’m not saying that trigeminal neuralgia is a simple model, but relative to spinal cord injury it is. One nerve, a big nerve, and the pain is in that nerve. I became interested in mechanisms and the patho-physiology of pain.

How is the Facial Pain Research Foundation unique from other research organizations?

We try to keep the bureaucracy at a minimum. We try to keep, while diversified, the number of projects we fund to maybe four, five, six at the most. We have a purely volunteer organization. Nobody gets paid anything. Our scientists don’t get paid. Our Trustees don’t get paid. Our support staff doesn’t get paid. I don’t get paid. Ninety-five percent of the money that comes in goes directly to the researchers for the research. I try to look for the best people in their field in the world to work for us. And to work with us.

How were you able to attract top researchers in the world to such a small foundation?

Instead of having them submit a grant, we say, this is what you’ve been doing, give me something we can hang a hat on, then go and do what you think will be exciting. So instead of their having to deal with a bureaucracy and submitting a grant every six months or a year, we, on a small scale, give them the money quickly, give them their leeway and see what they can do.  I call this “money with soul.” This is money given by people directly. This is not some faceless National Institutes of Health grant given with your taxpayer dollars. 

You were chairman of a prestigious neuroscience department and director of the McKnight 
Brain Institute.  Why is the Facial Pain Foundation’s research so important to you? Is it in part because a solution to neuropathic facial pain would also help provide scientific answers for multiple sclerosis, epilepsy, back pain, and other neuropathic pain?

Yes. I think it has a chance of making a difference. Mother Nature in my opinion is very conservative. The neurotransmitters in the gut are very similar to those in the brain, except you have different receptors and they work in a slightly different way. I look at this, and I think other people do too, as hopefully being sort of a Rosetta stone for pain, for neuropathic pain. Fundamental mechanisms are involved, and I think we can have a broader effect than just trigeminal neuralgia, also maybe diabetic pain and other pains. I think this research has a chance to be bigger than what you might expect it be.

How difficult is it to describe the science and the research to nonscientists?

For me, it is not too difficult. I’ve dealt closely in spinal cord injury and now in trigeminal neuralgia with the patient population we’re serving. I’ve always felt it was important to go to them and try to explain what we’re doing. I just hope that when I simplify it for lay people I’m not overdoing it so that I’m giving them incomplete or false information. 

At the beginning of 2011, the foundation set a goal of finding cures within ten years of establishing its research program.  At a minimum, what do you hope to accomplish before the end of 2020?

I’m hoping we will have a handful of genes or one gene we can hand off to others to test, and do animal studies and see if we can chart models of neuropathic pain by using the gene or the constellation of genes working together. To see if we have pain because they’re not working together, or we have pain because they’re overworking. Also, at the very minimum we hope we will have done human tracking with MRIs to chart the pain pathways that are involved, and locate the pain signal from the nerve to the brain, to where the brain can process it. And once you have that, then you have targets to do your intervention, do your injections. When you see which pathways are involved, you can define the neurotransmitters, so you can attack it that way. We are also hoping that the gene people will have solid data on how complex the gene interactions are – which is the alpha dog gene, or if there is an alpha dog gene, and how the genes interact.  

You wrote the following Facial Pain Research Foundation mission statement:

    “The Facial Pain Research Foundation is to establish a well funded translational research continuum that is dedicated to identifying the mechanisms underlying neuropathic facial pain and to developing groundbreaking therapeutic strategies that will permanently stop the pain of TN and related neuropathic pain syndromes.”

In your opinion, how are the foundation, its scientists, trustees and volunteers doing in relationship to its purposes and goals?

I think we’re doing fantastic, and I’m not someone prone to hyperbole. I’m very careful. I never would have dreamed in 2011 when we had zero dollars that we would now have collected a little more than $4 million. That $4 million has had a multiplier effect and raised even more funds for the research. I find that to be phenomenal. I think we are doing and our scientists are doing a wonderful job and making strong progress. I’m gratified and surprised that we have done as much as we have done in the period we have been in existence. 

Mervyn Rothstein Interviews Dr. Allan Basbaum



Dr. Basbaum spoke by telephone from San Francisco with Mervyn Rothstein, who was an editor and writer at The New York Times for 29 years before retiring in 2010.

Mr. Rothstein is now a columnist for Playbill Magazine, where he writes the “A Life in the Theatre” column. He has had trigeminal neuralgia since 2005.   





Dr. Allan Basbaum is professor and chairman of the Department of Anatomy at the University of California San Francisco. A neurobiologist, he is recognized worldwide for his work in understanding the mechanisms that contribute to the development of chronic pain, particularly the neuropathic pains produced by nerve injury, a condition that he considers a disease of the nervous system.

He is an expert in the use of neural stem cells to alleviate neuropathic pain in animals and has been rewarded by long-term funding of his research by The National Institutes of Health. He believes that his research has demonstrated that it is possible to repair damaged neural circuits. His work will have major consequences for neuropathic pain, including trigeminal neuralgia and related conditions, phantom limb pain and the pains generated in the course of cancer chemotherapy.  



1. Why did you decide to focus on pain in your career? 


That’s an easy one. It was the need for a summer job when I was a student at McGill University in Montreal. Now you’ll figure out how old I am, but I was trying to get a job at the [1967] world’s fair in Montreal. I was on the waiting list to get a job at the fair, which everybody wanted, and I couldn’t wait any longer. And I saw an advertisement for a summer research assistant, not at the fair but in the lab of Ronald Melzack. I had taken a course with him, and I got the job.


He’s one of the godfathers of pain research. He and Patrick Wall had published a major paper in 1965 called “Gate Control Theory of Pain,” which revolutionized the way people thought about what causes pain, why chronic pain develops. They argued that pain is not produced exclusively by the activation of “pain” specific nerve fibers, but rather by the balance of activity in different types of peripheral nerve fiber, small diameter nerve fibers that respond to painful stimulation and large diameter fibers that, in fact, respond to innocuous stimuli.  The latter nerve fibers have the capacity to regulate pain produced by the small fibers. Gate Control Theory provided a new perspective not only on ways to regulate pain (i.e. by increasing the activity of the large diameter fibers) but also on a mechanism for the generation of neuropathic pain (i.e., dysfunction or frank damage to the large fibers). My summer job in the Melzack laboratory started my research in pain mechanisms, and I’ve been doing it ever since. If I had received a job at the world’s fair, I might be doing something different.


2. What led you to believe that pain is a disease?


Well, I wouldn’t say that all pain is a disease. I refer more specifically to neuropathic pain, namely pain associated with nerve damage. There’s clearly persistent pain that results secondarily from a particular disease, for example, arthritis. You have inflammation in the course of severe arthritis, and the inflammation causes pain. We understand some of the mechanism by which arthritis causes it. If you weren’t able to treat the arthritis, the pain wouldn’t go away. So arthritis is the disease. Cancer that hits tissue causes inflammation and the tissue damage causes pain. If you could get rid of the tumor the pain would probably go away.


 Neuropathic pain is different in that the damage is to the nervous system, and the only consequence is pain, so in a sense the disease is the damage to the nervous system and thus pain, in effect, is the disease that needs treatment. The nerve damage could occur after spinal cord injury, it could be peripheral nerve injury, or more specifically it could be trigeminal neuralgia. We’re not quite sure what the nature of the nervous system damage is with TN but there has to be some pathology in the nervous system. That is TN’s feature – its main feature is pain. That’s it. So you can try to treat the pain by suppressing it with drugs, sort of damping it down, but you’re not really treating the underlying pathology. It’s different if you use an anti-inflammatory drug in a patient with arthritis. You can help the arthritis and coincidentally the pain gets helped. But in the case of treating trigeminal neuralgia, when you give a drug you’re not treating the underlying condition at all. You’re suppressing its manifestation. Our approach is to say, all right, is it possible to actually treat the condition itself, namely the disease itself, whose only manifestation is pain? That’s our objective, to repair the damage.


Neurological associations will probably never accept this notion. They have very specific criteria for what is a disease. But I also think that it’s very important for the public to understand that there is a disease element to this type of chronic pain. The public generally thinks of disease as things that kill you, like cancer, like MS or Alzheimer’s, where you eventually die. And so their focus is understandably on the disease and not the aspect of the disease, which is often pain that ruins a person’s life. People don’t die of pain, but they often die in pain.


 The public needs to understand that if you could address the chronic pain problem in individuals that have these other disease conditions you will dramatically improve their quality of life. In other words, rather than just focusing on the arthritis or the cancer, it is critical to also address the pain. What ruins people’s lives is the pain. People don’t realize that individuals with spinal cord injury who are in a wheelchair – if you look at them and you are empathetic because they’re paralyzed and you think that that’s the major problem they suffer, they will tell you it’s terrible that they’re paralyzed, but 70 percent of them have horrific pain that ruins their lives, perhaps more so than being in a wheelchair. If you can get rid of their pain they would be so much better off. But nobody sees pain so they don’t recognize it. I think if we explain to the public that chronic pain is a disease, an entity in itself, especially neuropathic pain, they will be a little more understanding and perhaps more committed to solving the problem.


3. What is the importance of this trigeminal neuralgia research study, and what potential is there for having an impact on the study of other diseases and possible cures?


Trigeminal neuralgia, No. 1, is to many people considered the worst pain you can have – not that any pain is good, but trigeminal neuralgia is one of the most debilitating.


 No. 2, we believe because it’s responsive, like other neuropathic pains – sometimes, not always – to anticonvulsive drugs, it is really a condition in which there’s loss of inhibition, so that the central nervous system is hyperactive, as it is in epilepsy. We use an anticonvulsant to reduce the hyperactivity. If that is the essence of the disease, it might be possible to repair, literally rebuild the nervous system and overcome the loss without using drugs, which even when they are effective often have horrible side effects. That’s the big problem – drugs can be good, but it’s very difficult to come up with a drug to treat these kinds of conditions without having side effects that make patients miserable.


 So the idea here is to literally repair the nervous system. And that’s the approach we’re taking. We believe we can use transplants of precursor, so-called progenitor cells that have the capacity to develop into inhibitory nerve cells and reconstitute the inhibitory controls that are missing.  In the course of our studies, I have not only been excited at our ability to treat animals that manifest hypersensitivity in models of neuropathic pain, but am also overwhelmed at how plastic the nervous system is. The adult nervous system will accept these transplants and the cells will integrate into circuits. The host nerve cells make synaptic connections with the transplanted cells, i.e. communicate with the cells, and the transplanted cells make connections with the host. As far as I can tell the new circuits are permanent. We’ve now gone at least six months and shown that these cells continue to make beautiful connections, so that it really is possible to take advantage of the plasticity and malleability of the nervous system. And in that sense we are really targeting a cure, not just some salve. We are not just trying to suppress the pain – we are actually trying to treat the condition that generates it. That’s why I’m so excited about it. And trigeminal neuralgia is one of many neuropathic pain conditions that I believe would be particularly amenable to this approach.


4. Are you developing the cell-replacement therapies to be used clinically to treat neuropathic pain (including trigeminal neuralgia) or are you using them as a proof-of-principle preclinical research tool?


Well, at the moment it’s preclinical, but the success we’ve had is incredibly encouraging. We began in the mouse because we were using embryonic cortical cells as the source of the transplant. These are cells from the brain of an embryonic mouse that we know are the cells that normally make all the inhibitory neurons in the cerebral cortex. Although these are not normally destined to become the inhibitory neurons in the trigeminal nucleus or the spinal cord, they will survive and grow in these regions.  And of course, they form connections and importantly can treat the mice in models of neuropathic pain. It’s a model that we believe mimics what is happening in the human with neuropathic pain.


So that is the first step. And that is a proof of principle, a very exciting proof of principle. Then the next step, which we’re doing, is using embryonic stem cells that have been modified to become inhibitory neurons. Here we’re talking about a human cell, human embryonic stem cells. And we transplanted them in the mouse, and they survive, grow and are functional.  We have to use immunologically suppressed mice otherwise the mice would reject the human cells. So now we have proof of principle that human cells can be effective in an animal model of the human condition.

What’s the next step? To get the cells to a state where you can actually reach the quality where you can transplant them into a human. There’s no question that our objective is to take this into the clinic.


 Somebody inevitably asks: when is this going to happen? I don’t answer questions like that because I honestly can’t predict. But is that our objective? Unquestionably. We’re working with the stem cell people at UCSF to get these cells to a condition where they can be used clinically, and I’m much more optimistic than I’ve ever been that we’ve got a handle on something that can work. It’s because of the remarkable ability of the nervous system, of its circuits, to be manipulated. I really didn’t think that the system was that plastic, but it is. The adult brain and spinal cord will accept those cells, I think in a therapeutic way.


5. This question is something you just alluded to, but when do you envision (or hope) that cell-replacement treatments for neuropathic pain (including trigeminal neuralgia) will be ready for use in humans?


 As I said, I can’t predict the future. There are so many steps hurdles that have to be crossed. The first thing is to get the cells to a state where the Food and Drug Administration would accept a transplant. That’s more a stem cell expert issue. We use the stem cells that our colleagues provide to us. They continue to address this need and of course the whole stem cell field is growing at a tremendous rate.  So I don’t think it should take too long to get the cells to that stage. Stem cell therapy is being used very preliminarily in other conditions now, and I think it’ll grow exponentially within the next five to ten years. With respect to chronic neuropathic pain we believe that we understand how the cells can be used and where they should be transplanted. So in my mind the major barrier is to get the stem cell people to tell us that yes, these things are ready to be put into people. We believe that the therapeutic proof of principle is established and that the fundamental biology, between what we’ve seen preclinically and what we believe occurs in humans, is solid.


 I am confident that the neurosurgeons are ready to take this to the clinic. They know about the work and are following it closely. I’m going to give a talk at the annual meeting of the Society of Neurological Surgeons. They recognize the need for a novel, exciting and feasible approach and want to learn more about what we are doing. But will it be next year? No. Five years? Possibly. I really don’t know.


6. Perhaps you’re already answered this question, but what are the biggest obstacles you face in translating your preclinical findings to the clinic?


It has to do with the quality of the stem cells, to be sure that they meet all the standards to put into a human. One needs to demonstrate unequivocally that the cells don’t become tumors, because there’s certainly an ongoing concern that some stem cells might become tumors. Our data so far says that the stem cells we’ve worked with do not become tumors. They don’t have tumor markers and are not proliferative. So that’s very encouraging. This is one of the major issues that one has to be concerned about.


Always, with any therapy, there’s the potential for adverse side effects. So far, we haven’t seen these in the animal models, but there may always be some unexpected adverse side effects when you use a new therapy. One of the first things, especially when you’re dealing with pain studies in animals, is that you don’t have motor side effects. We haven’t seen these so far – that’s encouraging. 


We’re talking about a therapy meant to rebuild parts of the nervous system, so it’s always possible there will be unexpected side effects. We don’t anticipate them, but those are the things we need to watch for. One of the first things you want to know is not so much does it work but is it safe. This is key. You’re dealing with a patient who has a long life span, so safety becomes incredibly important.  


7. The Facial Pain Research Foundation is moving forward with a sense of urgency to find cures for trigeminal neuralgia and related facial pain. Why have you linked your efforts to such a new organization in the field of pain research?


That’s an interesting question. Why? I usually don’t answer ‘why’ questions, but rather where, how and what. I recognize that these facial pains are among the worst pains that patients can experience. I believe that the neurosurgical approach to therapy is very feasible in these individuals. And the neurosurgeons agree. So the type of therapy we’re proposing, namely using transplants is rationale to the neurosurgeons, particularly as the target for transplantation is known and accessible. These are places the neurosurgeons have gone in previously, and it’s a very doable procedure. It’s a very discrete type of pain, and the area that’s involved is quite localized, to one side. That’s also advantageous.


Contrast that for example with a patient with chemotherapy-induced neuropathy, which can be associated with terrible pain. But here, for example, it can be in both hands and the feet. That’s a systemic, widespread disease, because the drug acts everywhere. For this reason it may be very difficult to pinpoint the particular area of the nervous system that you want to treat. But in the case of trigeminal neuralgia and facial pains, the target is restricted. It makes sense to target something that is so focused, because then the cells can really do their job. It’s a very tractable system.


And the other reason is that I was impressed with the Facial Pain Research Foundation, and its enthusiasm to get financial support. Our lab is well funded; that’s great, but these are expensive studies. And as I said previously, the study of pain is not something that the philanthropic world tends to support. Families tend to support the diseases that kill their loved ones, even though the pain clearly destroyed their quality of life.


8. Every day many people in pain are contacting the Facial Pain Research Foundation asking if it is truly possible to find a cure for trigeminal neuralgia. How would you respond to their questions?


Until we started this type of work, I would have said, “A cure, probably not; the idea is to come up with something that can ameliorate the condition better than what exists now.” Now we have a better understanding of the nature if you will of the neurological problem, of the damage that has occurred. As a result our approach is truly reparative, i.e. disease modifying. We want to rebuild parts of the nervous system, and in that sense we are trying to develop a cure rather than just to ameliorate. This is an unusual opportunity to dream of a cure rather than just palliative pain management.






Michael Pasternak, Ph.D., is a founding trustee of the Facial Pain Research Foundation. Dr. Pasternak

spoke by telephone from Florida with Mervyn Rothstein, who was an editor and writer at The New

York Times for 29 years. Mr. Rothstein now writes the monthly "Regional  Theatre" column for Playbill Magazine and is a former member of the Tony Awards Nominating Committee. His first symptoms of trigeminal neuralgia occurred in 2005.


The Interview




Mervyn Rothstein


Michael, how did the Facial Pain Research Foundation, a multimillion Dollar research foundation to find cures for trigeminal neuralgia and related neuropathic pain, become a reality?


I think, Merv, first I need to remind you that I had the pain. That I am a survivor of that facial pain. And I am in a very sought-after group to be in. Because there are few people of the thousands of trigeminal Neuralgia sufferers I’ve known that have been as pain free for as many years as I’ve been. So I feel very special. And there was a moment when I realized that it was time for us to work toward finding a cure.


I’d been involved with the Facial Pain Association, formerly the Trigeminal Neuralgia Association, for many years as a volunteer and in leadership roles after I’d stopped having the pain.  I was fortunate to have a successful microvascular decompression surgery with Dr. Peter Jannetta. I had been a businessman and a college professor, and I always felt, because my mother had told me that I could, that I could be successful at whatever I wanted to do. Then, in 2009, two other members of my family got facial pain. It was at that moment that I felt that we really needed to have a cure.


For 50 years, the treatments that have been given to trigeminal neuralgia patients have worked for only some people and not for others. So I connected with several friends who had been with the Association for years – Roger Levy, who had been the chairman of the board, and Mike Hirsch, who had been the president of the association after me – and we went down to Marco Island in Florida and spent three or four days talking about how do we put together a research foundation to find a cure for TN, and for related neuropathic pain.


And that’s what we did. We brainstormed – and there certainly wasn’t a roadmap – and we decided to find some talented people, creative people, who were willing to admit they didn’t know what they were doing but were willing to pull together and create a foundation to find a cure. I approached Al Rhoton [Albert L. Rhoton Jr., M.D., founding chairman of the department of neurosurgery at the University of Florida College of Medicine], the most famous neurosurgeon in the world, and Doug Anderson [Douglas K. Anderson, Ph.D.], head of the McKnight Brain Institute at the University of Florida, and we continued to talk about what it would take to put together a foundation, and we grew it. The focus was we were going to find a cure.


How are we going to get rid of all this pain?


We’re going to get rid of it because we have found the best consortium of scientists in the world to work on it. These are outstanding scientists whom we approached, and we pulled them together, and we said, “We need your help to do this.” It’s a hell of a challenge. Imagine saying we want you to work on the most difficult problem there is – how do you stop the worst pain known to humankind? Now we have five research projects, working on different approaches to finding a cure.*


The scientists in the consortium believe in the concept of synergy, that the whole is worth more than the parts, that each group’s research supports, affects and benefits the other groups’ research. These are great minds, and I believe they’re going to do it. That’s basically our motto – we can do this. There are hundreds of scientists working on these projects in the five locations. Our goal is believable. And it’s going to happen.


Where does all the money come from to support the foundation’s research projects? How much does the foundation receive each year?


That’s a very, very good question. First, we have thousands of volunteers who have created opportunities for people to participate in fund-raising activities – everything from comedy shows to golf events to running and walking and wine-tasting, music events, the whole range.  All of these are volunteer-based.


We have people who send us $1 a month and many who send us thousands of dollars a year. We also have companies like IBM that send us money. We’ve had a number of people who have given large sums of money as matching grants. The Wasdin family has given $120,000.  A matching grant of half a million dollars came from the Cilker family.


There are many ways of raising money, and it’s the first time in history that people have been asked to donate specifically to stop pain. We’re going after pain. Pain is the disease here. Because if we could end the pain, we could stop the world’s most painful condition – which is trigeminal neuralgia, and the conditions related to that.


How do you get people to volunteer?


Well, Merv, how did we get you to volunteer? We asked you, and you said yes. I would guess most of our volunteers are people who are in serious pain and have been unable to resolve it with surgeries or medications, or people who have experienced the pain but have been able to resolve it or ameliorate it with procedures or medicines. Family members and friends volunteer too. They all are doing the fund-raising hunting for us. And they find us on our web newspaper, The Afternoon Edition.


Tell me about The Afternoon Edition, which is at I understand it’s the most visited of its kind. It has no advertising, and yet has so much information and is read worldwide. How does it get its stories?


The Afternoon Edition is really the brainchild of Mike Hirsch, who is the Chairman of Whitehall Printing Company. Mike had the belief that if he could create a newspaper that would speak in simple, lay person’s terms, that would explain the science and the pain, that would tell the stories of the people in pain, and that would do so in a very personal way, it would attract readers to the newspaper. And he was right.


All the stories are written by volunteers. The newspaper also shares information about all the research. And it also provides an opportunity for people who want to volunteer and become part of the foundation to do so.


What’s the toughest part of your leadership role? What keeps you awake at night?


That’s a difficult one. I would say the toughest part is the larger and larger number of people contacting us who are in horrible pain. Who are disabled. Especially those families where children have trigeminal neuralgia. That keeps me up wanting to be certain in my mind that we’re providing the support necessary for our scientists.


And also my concern that we are properly saying thank you to all those who are helping us. Sometimes I’ll pop up in the middle of the night and think, for instance, did I thank Frank Skoviera for all he’s been doing? That keeps me awake.


We’re at the point where the research is a reality. It’s over the hump. The foundation is happening. It’s no longer a question of whether it will happen. The scientists are working, and we’re waiting for the babies to be born. I go over and over in my mind, are we providing enough support for them? And are we

responding effectively to the people who are in pain and trying to keep their hopes up? Hope is important. This has been called the suicide disease by some, and you and I both know there has been a journalist

recently who took her life because of the problems related to the pain – she couldn’t stand it anymore. So dealing with those difficult situations sometimes keeps me up as well.


Why didn’t this research start many years ago?


I think we were naïve enough to think that the medical professionals – many of the neurosurgeons and neurologists – were going to solve the problem themselves. I think we were also ignorant enough that when they were giving us data – I mean outstanding surgeons, we’re not talking about quacks here, who were saying that on a good day they could fix 80 percent of the people who came into their offices – we forgot about the 20 percent, hoping we’d be part of the 80 percent.


But it became more and more important to look at that 20 percent and those whose pain returned later in spite of the surgery. We needed to also look at those who couldn’t have surgery and reacted badly to

medications.  These are the people who are going on disability, who are in horrible pain. It got to the point where even though in our earliest organization we said that research as an important goal, it wasn’t research to find a cure. It was research to better understand the disease, better understand how it affected patients. But it became apparent that we simply had to change, that we had to focus on the cure. It just took us time. I think we believed it was going to happen, but it didn’t happen.


At one point, we brought together seven neurosurgeons and neurologists in a room and interviewed them and asked them what they would do if we gave them all the money they needed to cure trigeminal neuralgia, and they didn’t have a clue. So we understood that we were speaking to the wrong group. That we really had to speak to the scientists and get to the basic science of what’s causing this problem in the nerves and the brain. And that’s what we’re doing.



How do you respond when someone asks you if the foundation’s research projects are really going to find the cure? What do you say to health professionals who say that there can never be a cure for trigeminal neuralgia and related neuropathic pain?


For the health professionals, I just ask them what planet they live on. In pretty much the last hundred years, it’s not much more than that, we’ve learned how to fly, created the Internet, found a cure for polio. One of our major reasons for starting the foundation was Mike Hirsch’s talking about President John F. Kennedy, who said let’s put a man on the moon in the next 10 years. Think about it, Merv. If you could put a man on the moon in 10 years you sure as hell ought to be able to fix a nerve in 10 years. That’s been one of our driving forces. It’s let’s get it done. Get the necessary resources together. Be very focused.


I’ve had some health professionals look me in the eye and say the only one who can solve this problem is God. And sometimes I feel like telling them, look, God put Al Rhoton and Mike Hirsch and Doug Anderson and the rest of us on this Earth to solve this problem. And we’re here and we’re going to get this done.



The Facial Pain Research Foundation Consortium


* “Nerve Myelin Repair and Growth,” Dr. Lucia Notterpek, University of Florida McKnight Brain Institute; “Cell Replacement Therapy as a Treatment for Injury-Induced Neuropathic Pain,” Dr. Allan Basbaum, University of California, San Francisco;  “Finding the Genes that Predispose to Trigeminal Neuralgia,” Dr. Marshall Devor, Hebrew University of Jerusalem, Israel, Dr. Kim Burchiel, Oregon Health & Science University, Dr. Ze’ev Seltzer, University of Toronto;  “Mapping Towards a Cure:

Identification of Neurophysiologic Signatures of Trigeminal Neuralgia Pain,” Dr. John Neubert, Dr. Mingzhou Ding, Dr. Marcello Febo, Dr. Robert Caudle, Dr. Todd Golde, University of Florida McKnight Brain Institute; “Novel Ways to Deliver Compounds That Can Eliminate the Pain of Trigeminal Neuralgia,” Dr. Wolfgang Liedtke, Duke University. Dr. Scott Diehl, Consultant, Rutgers University.

Facial Pain Research Foundation International Research Coordinator Dr. Joanna Zakrzewska, UCLH NHS Foundation Trust, London UK.




Columnist Mervyn Rothstein


Interviews Dr. Kim Burchiel



Dr. Kim Burchiel is a co-principal investigator in the Facial Pain Research Foundation’s trigeminal neuralgia project. As the John Raaf Professor and Chairman of the department of neurological surgery at the Oregon Health & Science University in Portland, his interests include functional and stereotactic neurosurgery, pain surgery and epilepsy surgery. His colleagues in the trigeminal neuralgia project are principal investigator Dr. Marshall Devor of the Hebrew University of Jerusalem, Israel, and Dr. Ze’ev Seltzer, a professor of genetics at the University of Toronto. The project is called "In Search of a Cure ... Finding the Genes That Predispose to Trigeminal Neuralgia." Its goal is to identify the genes that make people susceptible to TN or cause the pain, and then move toward prevention and cure.


Dr. Burchiel spoke by telephone from Portland with Mervyn Rothstein, who was an editor and writer at The New York Times for 29 years before retiring in 2010. Mr. Rothstein is now a columnist for Playbill Magazine, where he writes the "A Life in the Theatre" column; he is also a member of the Tony Awards Nominating Committee. He has had trigeminal neuralgia since 2005.


Some people are surprised that a person of your professional stature in the world of neurosurgery is involved in research that has a DNA focus.  Why have you decided to take on a leadership role in this genetics research project?


I’m more committed to solving the problem than I am to any particular solution. So if it turns out that we can discover the origins of this condition it may well be that surgery may not be the ultimate answer.


Why have you decided to focus on pain in your career? 


Very few neurosurgeons choose to focus on pain, because it is a difficult specialty. It’s often frustrating for both the surgeon and the patient. It actually involves the surgeon frankly saying at some point, "I don’t know. I can’t help you." And surgeons hate that. They like to have an answer. And you have to be honest enough and humble enough, I guess, if that’s possible, for a surgeon to say, "I don’t know what’s wrong with you." The flip side of that, honestly, is so much can be done in the pain world. Pessimism didn’t cure anything. You have to approach this with optimism and with science. I think those two things go a long way. A lot farther than most people would think.


What is the importance of this study, and what potential is there for having an impact on the study of other diseases and possible cures?


I am excited about this research because the opportunity here is enormous. Not just for understanding trigeminal neuralgia but understanding neuropathic pain of other forms, which is a general condition that has been to a large degree the Holy Grail of pain research for my entire career.


What steps have you taken to be certain that the DNA samples that are being collected are from people who have experienced trigeminal neuralgia?


We developed a way to describe and define trigeminal neuralgia which is quite precise. This is a so-called Type One trigeminal neuralgia which in the past has been called classic trigeminal neuralgia. But we put a definition around that which made the separation of people with this condition very clear from people that don’t have the condition. And that’s the first time that’s been done.


We understand that at OHSU you are approaching the collection of the first 100 patient DNA samples and that the goal is to complete another 400 at eight additional Collection Centers.  When do you think that the total 500 will be collected and what will that number provide your research scientific team?  


We are in the process of getting the other centers up and running right now and my expectation is that within about a year to 18 months we’ll have all the samples collected we need to complete the DNA collection. And then the genomics, the genetic side of it, will take another six to nine months, my guess.


What are the "next steps" in moving toward a cure after the collection (phenotyping) is completed?


The collection is simply getting the DNA, but the most important thing now is to run these samples on a gene analyzer that will give us an enormous amount of information. But the information has to be processed in such a way as to make sense of the information. So this really would come under the heading of Big Data. We’re going to get an enormous amount of data. The heavy lifting is the analysis of the data, to make sense of it. Because we’re talking about analyzing millions of genes per person. We’re going to get an enormous amount of information. So it’s what’s called Informatics. The data processing is going to be the really big part of this process.


The Facial Pain Research Foundation is moving forward with a sense of urgency to find cures for trigeminal neuralgia and related facial pain.  Why have you hitched your efforts to such a new and relatively unknown foundation for pain research?


Well, first of all, they approached me. That’s a simple answer.


But why did you agree?


I agreed because I think trigeminal neuralgia is a unique opportunity. Because of the clarity with which we can make this diagnosis we have an opportunity to explore a condition with what we think is a very uniform population that has the potential to produce an answer. When we talk about other pain conditions the variation is so great that the ability to extract the common signal from the data is extremely difficult. But trigeminal neuralgia is such a clearly and precisely defined entity that there’s no mistaking it for something else, and in that way what we’re doing is proving the resolution of our data, meaning we’re going to get a much clearer picture of what’s going on.


Each day people are contacting The Facial Pain Research Foundation with stories of failed surgeries and medications they experience in trying to stop trigeminal neuralgia pain...that their pain is getting worse.  What encouraging words do you have for these people? 


The most encouragement I can offer is that treatment of pain is a very difficult enterprise. For patients with trigeminal neuralgia the prognosis for treatment is actually quite favorable. Obviously any treatment of any type will have some patients that fail tradition therapy. And it’s hard for someone who has failed the therapy to be appreciative I guess of the fact that most people actually do therapy well. I think the things I can tell someone who’s failed therapy is to make sure they’re seeing in terms of a consultant the right person, someone who has experience and has committed, dedicated experience in this area. Because only in that way will they get what I think is the best possible answer, not only for what they have, why they might have failed and what the next steps would be, but also what not to do, because many people with failures go off and have further treatments that may be either ineffective or dangerous. So if you’ve failed once, if anything it makes it even more critical that they find someone that really knows the field and is committed to this diagnosis, to get the best possible suggestions for further therapy.


How can they help the scientists working toward cures?


I think right now the centers we’ve recruited – I think it’s going to be important to support those centers so we get the right numbers of folks in the near term, to go ahead and get our 500. We hope based on that additional data collection and the run that we do with it with the genetic studies, that we will obtain either an answer or at least clues to what the next steps might be for us. We have a lot of other ideas about things we might pursue. For example, we have talked about and will be doing some preliminary analysis on individuals that are said to have family that has had a trigeminal neuralgia past. That could be a difficult analysis because often we don’t have those other family members available and we can only validate the diagnosis within other family members if we have those people at hand. So if there were people out there – they’re probably not very common – that had a blood relative that had a bona fide case of what we call Type One trigeminal neuralgia, those people we really want to talk to, because that might give us some clues about the inheritance of this condition. We don’t believe though that this is a simple genetic inheritance. It must be multiple genes that contribute if it is genetic, which we do think it is. So family members with Type One trigeminal neuralgia would be highly valuable particularly if we can talk to them and sample their DNA.


That’s one way they can help. And the other is just to support the Foundation in its work. This is just the beginning. We have many other projects that the Foundation is going to be pursuing. This is where patients and families of patients with facial pain can really make an impact, because they can direct their resources to these very, very specific questions that are driven by what I think are world-class experts like Dr. Devor, Dr. Seltzer, myself. So even though it’s not a common condition, it is a very pivotal condition and one that the support groups can get behind and really move this forward. It may not only advance, as I said before, the treatment of this condition but many, many other pain conditions once we begin to crack the code.


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