First Published Oct 31, 2012

 

 

Unlocking DNA to Find A Cure For Trigeminal Neuralgia

    

Dr. Marshal Devor      Dr. Kim Burchiel         Dr. Ze'ev Seltzer

          

Imagine unlocking the mysteries of DNA that are so extraordinary and then applying those learning’s to finding a cure for the worst pain known to humankind.

Our DNA functions as the building blocks, or blue prints of life.  We all carry these building blocks within every cell of our body.   For many years patients have asked themselves and their doctors “why me?

Why did I get this awful painful condition called trigeminal neuralgia?...Why do I suffer so and others don’t understand...why do I feel like I could simply die?”

The Facial Pain Research Foundation’s first international research project to find a cure is underway and it seeks to discover the answers to “Why Me?” and lead scientists to developing a cure.

The Foundation’s Trustees are excited to announce their fourth research project entitled “In Search of A Cure...Finding The Genes That Predispose to Trigeminal Neuralgia”. It’s goal is to identify the genes that make people susceptible to TN or cause the pain and then move toward prevention and cure.

 Dr. Douglas Anderson, Foundation Trustee and Director of Research Programs, first presented the concept that there was likely a genetic basis for TN at the 2004 TNA National Conference in Orlando. He always found it odd that the anatomy of compressed nerves/lesions were seen in a significant number of individuals but only a few had TN. He always harbored the idea of identifying a genetic profile in TN patients that would lead to ending the painful condition. Anderson says “If there is a history of a member of your family having TN, other members of your family could be screened and hopefully the condition could be prevented by having the genetic pattern altered so the pain will not develop.”

 Dr. Joanna Zakrzewska of London England, the Foundation’s International Research Coordinator, asked Dr. Marshall Devor in March 2012 to prepare a research project proposal to seek a cure for TN and present it to the Foundation.

After seven months, the researchers and the Foundation Trustees have approved the research project and are excited about moving forward. The three Principal Investigators of the project are Dr. Marshall Devor, Dr. Kim Burchiel and Dr. Ze’ve Seltzer. 

The team of international scientists is led by Principal Investigator pain research pioneer Dr. Marshall Devor of the Hebrew University of Jerusalem, Israel. The award winning scientist has had an outstanding career in pain research. He has contributed an outstanding body of research, authoring several hundred papers over 40 years and has been been described as one of those “who view excellence as a way of life and the fulfillment of human potential as essential to creating a better world for future generations.”

 Dr. Kim Burchiel is the Chairman of the Department of Neurological Surgery at the Oregon Health & Science University in Portland, Oregon. Burchiel has been a long time member of the TNA Medical Advisory Committee and performed hundreds of TN surgeries. A successful researcher, he has been a national leader in the treatment of orofacial pains including TN. The first step of the research project, phenotyping and DNA collection, will be the responsibility of Professor Burchiel at OHSU. He is a leading authority in the phenotyping of facial pain conditions and author of the most widely accepted TN classification scheme. Dr. Burchiel has said: “this research project could be the most important pain study ever attempted” and he is very hopeful that it will lead to a cure for TN and related neuropathic pain.

Dr. Ze’ev Seltzer, Professor of Genetics at The University of Toronto, Canada is also an award winning scientist. He has dedicated his career to the study of pain. Seltzer says “ I am looking forward to be a Co-Principal Investigator in the TN project, bringing 35 years of studying the neurobiology of pain.” Having had many competitive grants and honors he has an outstanding track record of productivity in the field of pain and pain genetics. Seltzer also says “The goal to find a cure is achievable...our best salvation may come from genetics”.

 Consultants to the research project include: Dr. Joanna Zakrzewska, Eastman Dental Hospital, London, England...Professor Ariel Darvasi and Dr. Sagiv Shifman, Hebrew University of Jerusalem, Israel...and Dr. Scott Diehl, University of Medicine and Dentistry, New Jersey.

If you have any questions or comments please address them to the Foundation at: This email address is being protected from spambots. You need JavaScript enabled to view it..

Success in answering critical questions about the role of genes in TN and other 

nerve-related facial pains relies on private support. Here are ways in which donors

at all levels can join The Facial Pain Research Foundation in finding a solution:

• Support full expenses of one patient in the study:        $1,770
• Pay for the genotyping of one research participant:      1,100
• Help with the phenotyping costs for one participant:      600
• DNA extraction from one person’s saliva samples             40
• Pay for saliva kit & shipping cost for one participant       30

 

Facing My

 

Facial Pain: Merill

 

 

By Hanna Shae Smith

Author byline: Hanna Shae Smith is an award-winning journalist, student clinician, and daughter of a person with Trigeminal Neuralgia. Smith lives in Phoenix, Arizona, where she studies chronic pain neuropsychology and neuroscience, teaches emergency basic life support, and volunteers doing search and rescue/recovery.

 

Research funded by the Facial Pain Research Foundation

provides insights into the role of brain inflammation

in patients with Trigeminal Neuralgia

 

By Jerry Krbec MBA

At the last Society for Neuroscience Annual Meeting, research conducted by professors John Neubert and Mingzhou Ding and their colleagues, supported by the Facial Pain Research Foundation was presented. The name of the presentation was “Free Water as a Neural Marker of Trigeminal Neuralgia”. This research was part of the FPRF focus on identifying pain pathways in TN.

Imaging free water is a new methodology based upon diffusion MRI. Measuring the level of free water between cells in brain structures indicates the level of neuroinflammation present in those structures. The role that inflammation plays in TN is currently being hotly debated, so this was very topical and timely research.

Previous analysis done by the team had shown that of all the brain white matter structures imaged for free water in TN patients, the pontine crossing tract (PCT), which is a white matte tract close to the trigeminal nuclei, showed particular sensitivity to TN-related neuroinflammation. The PCT connects signals from the brainstem to the cerebellum and may also include part of the tract that links the trigeminal nerve to the thalamus. The thalamus is the area of the brain that routes most pain signals, including TN pain, to higher brain levels where pain is actually perceived. They imaged 27 patients that had TN1 or TN2 with and without surgical treatment.

In the TN1 non-surgical group, the level of inflammation correlated very tightly to the length of disease duration in these patients. (See Fig. 2.) This means that the longer a patient had TN, the more inflammation was present in their PCT. In the TN1 patients with prior surgery, there were still high levels of inflammation measured but the amount of inflammation no longer correlated with disease duration. For some reason surgery seems to not decrease the inflammation present, but it does disturb the relationship between neuroinflammation and disease progression.

In TN2 patients with or without surgery there was no statistically significant relationship between disease duration and inflammation, suggesting that there is a difference in the cause of the two conditions. (See Fig. 3.)

This study has revealed much about the role of inflammation in the brains of TN patients. We have learned that in the brain white matter of TN patients, the only location with significant inflammation present is the pontine crossing tract (PCT). The PCT is in the same area that gives rise to the trigeminal nerve, and from where trigeminal pain signals are transmitted to the higher levels of the brain. Inflammation anywhere in the body normally causes pain so this obviously provides researchers with a new target area to direct therapies towards.

It was also found that the amount of inflammation in the brain of TN1 patients increases the longer they have had the disease which may indicate some sort of cumulative impact or progression of the disease over time. The finding that this same relationship over time doesn’t hold true in TN2 patients or patients that have had surgery makes the issue of inflammation and disease progression more difficult to understand. The data maybe providing more conformation that there are differences in the mechanisms causing TN1 and TN2 pain which may be why the progression relationship is lost. While more research is needed to unravel what is occurring, this study also validated the usefulness of using the measurement of free water levels to tract the inflammation that is present in the brain.

 

 

 

 

Mervyn Rothstein

 

Interviews

 

Cory R. Nicholas Ph.D.

 

 

 

 

 

Cory R. Nicholas, Ph.D., is a Founder and the Chief Executive 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 he studied brain development.

Dr. Nicholas pioneered methods to obtain inhibitory nerve cells, or interneurons, from human 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 inhibitory interneuron cell-based therapy to treat chronic disorders of the nervous system, including neuropathic pain. Dr. Nicholas and his co-founders, John Rubenstein, M.D., Ph.D., Arturo Alvarez-Buylla, Ph.D., and Arnold Kriegstein, M.D.,Ph.D., were the first to discover that this type of cell therapy could inhibit and rebalance hyper-excitable neural networks in animal models of relevant neurological disorders – that the injected interneuron precursor cells could integrate into neural circuitry, 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 whether the Neurona interneuron cell therapy can stop neuropathic facial pain in animals. The study should take from 12 to 24 months. If it is successful, Neurona plans to work toward Food and Drug Administration approval to begin clinical trials in humans in the future. 

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 playbill.com, 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 neurobiologist and I was studying brain development, specifically the development of inhibitory nerve cells that are the basis of the collaborative work with the Foundation. We have a close colleague at the University of California at San Francisco, Allan Basbaum, Ph.D., who was very interested in seeing if these inhibitory cells could be applied to the treatment of neuropathic pain. So our groups joined forces, and Dr. Basbaum’s laboratory pioneered the application of the inhibitory interneuron transplants that we were studying in the rodent brain and applied them to the spinal cord in rodent models of neuropathic pain. And he was able to show that the transplantation of those neurons could ameliorate and in some cases completely reverse the experimental pain hypersensitivities in animal models. In part because the results were so exciting, we decided to launch a neuropathic pain program at the company.

What is the importance of this Trigeminal Neuralgia research study?

I think this is a tremendous opportunity to build upon the work from Dr. Basbaum and our group, to leverage the resources and expertise from the Foundation and translational savvy Neurona, and to determine whether the human interneuron cell therapy is feasible, safe, and effective in an 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 an animal model of this disease. These animal models are quite nuanced and can be difficult to establish from scratch. Then, we were introduced by the Foundation to Dr. John Neubert at the University of Florida, who has this model established in his laboratory and developed behavioral tests to measure experimental facial pain in rodents. Thankfully Michael Pasternak and the Foundation were able to make that introduction.

We submitted a proposal to the Foundation that was just funded where we will do three things. Number one, we can see if the pain phenotype – the observable pain characteristics – can be extended to an animal that does not have an active immune system. We need an animal model that does not have a functioning immune system to allow for the long-term persistence of the human cell therapy in a rat. So we had to change the animal strain – that is the first aim, to see if we can produce a stable pain phenotype in an immunodeficient animal model of Trigeminal Neuralgia.

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

And then finally, if we succeed with the first two aims, to next determine whether the human interneuron cell therapy can exhibit disease-modifying activity and compelling pain reduction in this rodent model. If we successfully accomplish these aims, then I think we can justify the pursuit of a future 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 we could consider proposing a first clinical trial. But those would be the next steps.

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

Neurona is a pre-clinical stage biotechnology company developing neural cell therapies for the treatment of chronic diseases affecting the nervous system. Our lead product is a cellular therapeutic comprised of inhibitory nerve cells that we are developing for chronic focal epilepsies, neuropathic pain syndromes, and neurodegenerative diseases such as Parkinson’s. We are planning to launch our first clinical trial for epilepsy next year. Neurona now has ~50 employees who are passionately working around the clock to advance our novel cell therapies into the clinic. We are fully committed to creating safe and effective cell therapies for chronic disorders of the nervous system through rigorous science, collaborative innovation, and groundbreaking regenerative technology. 

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 in rodents with Dr. Neubert is between one and two years long. And then it would probably be another two to three years of working with the FDA before a first-in-human clinical trial could be considered.

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 to just about any disease, especially in the neurological space because rodents are different from humans in many aspects. There are different anatomies, different neural circuitries, and the added difficulty with studying pain in animals, where you don’t typically know how an animal such as a rodent is feeling. Since a rodent can’t tell us if they are in pain, we use surrogate measures of aversive behavior or hypersensitivities, such as how the animals are moving their limbs or responding to stimuli. Those surrogates are of course never the same thing as asking a person if they’re experiencing pain.

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 in the field of pain research?

We were looking for ways to apply our regenerative cell technology as a therapeutic for people living with devastating, treatment-resistant diseases. Pain had been an important potential indication for the company. Through the Foundation, we then heard the stories of people who are suffering with Trigeminal Neuralgia. It really pulls at your heartstrings, and you want to do whatever you can to help. Additionally, Trigeminal Neuralgia may be a rational indication for a restorative cell therapy. Neurona’s cell therapy is administered locally. In Trigeminal Neuralgia, there’s a focus of pain in the facial region that may be triggered in the trigeminal ganglion and may serve as a good target for local injection of the cell therapy.

However, the causes of chronic neuropathic pain are still quite controversial in the field and nobody knows for sure. It gets back to your question about what makes it difficult to translate preclinical research to humans. Another important aspect as to why this is a tough bridge is that it is challenging to establish a relevant and predictive animal model when we don’t really know yet what causes this disease. It is therefore not surprising that most drugs that work in animal testing often do not work in humans.

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 therapy, and cell therapy approaches, like ours. So I think there have been very rationally thought-out efforts to try to better understand and treat the disease, and we remain hopeful that a cure is possible.

What keeps you awake at night?

Other than the global pandemic now upon us, fundraising is paramount. Drug development is a slow and expensive business, especially for cell therapies. This is why we are so grateful to the Foundation for supporting the proof-of-concept study with John Neubert to determine whether the inhibitory neuron cell therapy can be efficacious in rodents. The Foundation has done a terrific job in seeding projects like these to take that important first step. If successful, we will need to raise additional funds to march this therapy toward a potential first clinical trial in human.

Beyond fundraising anxiety, it is always whether or not we will be able to build safe and effective therapies that can truly make a difference to significantly improve quality of life and revolutionize medical treatment for those living with chronic diseases. To achieve this ultimate goal, it will take all stakeholders working together, from researchers and clinicians, to investors and regulatory bodies, to patient advocates like you. I sincerely hope and expect that we will succeed.

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 Playbill.com, 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.

MR: YOU ARE BOTH A NEUROLOGIST AND NEUROSCIENTIST.  WHY DID YOU DECIDE TO FOCUS ON PAIN IN YOUR CAREER?

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.

WHAT IS THE IMPORTANCE OF YOUR TRIGEMINAL NEURALGIA RESEARCH STUDY AND WHAT POTENTIAL IS THERE FOR HAVING AN IMPACT ON THE STUDY OF OTHER DISEASES AND POSSIBLE CURES?

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.

WHY HAVEN’T SCIENTISTS COMPLETED THIS RESEARCH YEARS AGO? WHEN SOMEONE ASKS YOU WHY DIDN’T YOU START THE RESEARCH MANY YEARS AGO HOW DO YOU RESPOND?

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.

YOU SEE PATIENTS IN PAIN EVERY WEEK.  DO YOU REALLY BELIEVE THAT CURES CAN BE FOUND FOR THIS DISORDER, WHICH IS OFTEN CALLED THE “SUICIDE DISEASE”?

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.

WHAT ARE THE BIGGEST OBSTACLES YOU FACE IN TRANSLATING YOUR PRECLINICAL FINDINGS TO THE CLINIC?  WHAT ARE SOME OF THE WAYS YOU HOPE TO OVERCOME THEM?

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.                                           

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? AND HOW IMPORTANT IS THE FACIAL PAIN RESEARCH FOUNDATION TO YOU AND YOUR WORK?

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.

Facing My Facial Pain

 Tiffany Lynd

 

 

 

 

 

By Hanna Shae Smith

 

Hanna Shae Smith is a writer for the Facial Pain Research Foundation, award-winning journalist, student clinician, and daughter of a person with Trigeminal Neuralgia. Smith lives in Phoenix, Arizona, where she studies chronic pain neuropsychology and neuroscience, teaches emergency basic life support, and volunteers doing search and rescue/recovery.

 

    Tiffany Lynd was only 18 years old when she first experienced the pain of Trigeminal Neuralgia. Eighteen, at the precipice of the rest of her life. Eighteen, anticipating all that could be subsequent. Lynd dreamed of working in sports – never that she would begin experiencing symptoms of facial neuralgia her senior year of high school.

    The pain began on the lower, left side of her face and is described as “stabbing” and “sharp” – like an icepick or burning rod stabbed into her cheek. Lynd was examined by local physicians in her small Ohio town, however, was told at the time that it was unlikely she was experiencing Trigeminal Neuralgia.

           “Everyone kept telling me, ‘you’re too young,’” Lynd says, a response which prompted visits to neighboring cities for consultation with specialists.

It was an oral surgeon first spoke the words that would change her life forever: Trigeminal Neuralgia.

           “It changed my whole life,” she says. “I didn’t go to college because of it. It just changed the whole course of my life.”

    The time span between first symptom onset and diagnosis was 1.5 years. Prior to her symptoms, Lynd was entirely unfamiliar with chronic pain disorders. She took to the day’s prominent social media platform Myspace, seeking connection with those who could empathize over a shared diagnosis, and was grateful to find a couple such individuals. However, in a time when the internet was not the well of information it has since developed into, Lynd relied on public libraries for literature on her illness – a search which yielded few results. So began her journey for knowledge and relief.

TREATMENT JOURNEY

    Lynd’s diagnosing oral surgeon initially prescribed pain medication and she was subsequently given the nerve-pain-reducer/anticonvulsant Carbamazepine from an emergency room doctor. However, Lynd soon discovered that not only was she allergic to Carbamazepine, but also muscle relaxant Baclofen and nerve-pain-reducer/anticonvulsant Topamax. Although Lynd was prescribed anticonvulsant Gabapentin for several years, she ultimately made the personal choice to stop taking the pain medication after it stopped providing relief.

She now only takes her thyroid medication and blood pressure medication whenever she has a pain flare. Additionally, she has taken Fentora, a pain medication. The prescription regularly costs $8,000 per month for 112 pills, however, a grant allowed her to receive it free of charge. That cost is for the 200 milligram pills and increases per milligram amount. To replace Fentora, Lynd and her doctors are researching medical cannabis, which is legal in Ohio.

           “I have not tried it before,” she says. “My family doctor is all for it. … I’ve tried CBD oil where you just drink it. But, it just kind of relaxes you.”

    Lynd says while she has had a largely good experience with insurance companies paying for procedures, receiving assistance for medication can often be difficult.

           “They don’t want to pay for them or don’t think you need them,” she says.

    Lynd has been seen at seven hospitals and has undergone 17 surgeries, her first being a Gamma Knife Radiosurgery in 2000, which provided relief for approximately 11 months. She was then seen at the Mayo Clinic where she underwent a microvascular decompression in 2002. Several compressions of the nerve were located at that time, leading doctors to believe that the disease occurred from congenital malformation and subsequent compression. Lynd experienced pain relief following her 2002 MVD for five years.

    Following the return of her pain, Lynd underwent multiple Percutaneous Rhizotomies and MVDs. During one operation, the surgeon severed the sensory portion of the trigeminal nerve in an effort to achieve numbness of the face. However, the pain persisted and resulted in a diagnosis of anesthesia dolorosa – translated: “numb pain” – in which a misinterpreted pain sensation continues in the affected area despite the nerve’s touch sensation being either eliminated or diminished. Lynd subsequently underwent another operation in 2012 with the intention of entirely severing the motor portion and re-severing the sensory portion of the nerve. The pain, however, returned worse than before after approximately six months. Additionally, Lynd is now deaf in her left ear and blind in her left eye. She is unable to chew food and is only able to consume soft foods and liquids. Lynd says she now regrets severing the nerve considering how it has negatively impacted her specific, individual case.

COMING TO TERMS

    Undergoing multiple surgeries in hopes of relief, only to have the pain return is indescribably challenging, Lynd says. There were times she did not know if she could go on.

“There’s no explaining when the pain comes back, the fear and frustration. You feel so let down,” she says. “I had a neurosurgeon who told my parents that, ‘she’s either going to kill herself or she’s going to accidentally overdose.’ But, I think through God and my kids, I got through.”

    Lynd’s sons: 15-year-old Eli and 17-year-old Isaiah. Her voice comes to life when she describes them as her motivation, purpose, and reason for living.

           “I don’t know where I’d be without them,” she says.

    Lynd acknowledges that her children have been affected negatively by Trigeminal Neuralgia, yet she says she is grateful for their continued love and support.

           “They tell me it’s made them better people,” she says.

    It’s difficult for Lynd to pinpoint exactly how TN has changed herself, however, considering that it’s been part of her life for 25 years – and especially because symptom onset began at highly pivotal developmental age.

“I have lost a lot of memories [as the result of multiple operations],” Lynd says. “I don’t remember a lot. A couple of the surgeries were really rough afterward. I was in the hospital because of brain swelling. People will send friend requests on Facebook that I supposedly went to school with. I don’t know who they are anymore. … You may have known Tiff back then, but the Tiff now is Tiff 2.0.”

    Lynd also sees in herself some of the same tendencies that young, frightened teenage girl employed for protection.

           “I still push people away. In my mind, I’m protecting them,” she says. “I know that’s hard to let people see you vulnerable. A lot of times, people don’t know the situation. I feel isolated. Sometimes you feel people will look right though you.”

    TN entirely rerouted Lynd’s life, forcing her to rediscover herself and set a new course. She aspired to work in the sports industry prior to her symptoms onset and instead had to adapt to jobs in which she would not be forced to talk for long periods of time – beginning initially as a realtor and later transitioning to loan processing and then a loan officer. She has learned to adapt to her situation. Lynd’s typical day starts when she sends the kids off to school. The rest of the day is spent staying busy to keep her mind off the pain. She is highly involved with the boys’ education and enjoys cooking and baking in addition to doing yoga and meditation to find a measure of mental and emotional relaxation. She is an avid sports fan – especially football and the 49ers – and enjoys attending games and playing basketball with her kids. Lynd is also a writer, composing poetry and keeping journals documenting her thoughts and feelings.

           “It’s a good way to get my frustration out,” she says. “I went through a lot of different emotions. I deal with a lot of anger. Anger at the whole situation.”

Often, she has difficulty sleeping due to the pain and typically does not sleep well or through the night. Lynd keeps record of her attacks and says that she is “electrocuted” about 200-250 times per day. The burning sensation, however, never is mediated. Nerve blocks do not assist with the burning pain.

    One aspect of Lynd’s personality which she knows if gone, is a carefree nature. Simultaneously, despite everything which has changed, she says TN has taught her to be deeply appreciative for what and who she has in life.

           “I take advantage of the good days because they don’t come along very often,” she says. “The main thing that’s changed is that I never take anything for granted anymore. I am just so lucky and blessed to wake up and live the life I do every day.”

FACING THE FUTURE

    Lynd experiences Trigeminal Neuralgia on a daily basis and continues to make plans for future treatment. She is currently scheduled for a motor cortex stimulation, which will be her 18^th surgical procedure since diagnosis.

           “(The surgeon) said he’s done it on others who have had the nerve cut and they have gotten some relief,” she says. “He said, ‘I bet you’d take 10-percent relief.’ I said absolutely.”

    Lynd also continues the nerve blocks which she receives every 2-3 months. The relief typically last about 5-7 days and does not touch the burning pain sensation. She says she is grateful for what relief she gets, however.

    There have been excellent doctors in Lynd’s life, mingled with some who have made the situation more difficult. She encourages medical professionals to listen to patients, be honest, and become more educated on chronic pain disorders.

           “They need to be more educated and not jump to conclusions,” she says. “Some of them are so rude. Listen and be more understanding. … I’ve been to the ER and had a doctor look at me like I’m nuts. It’s just frustrating.”

    To family members of those with chronic pain, Lynd encourages expressing compassion even if empathy is impossible. Since day one when her TN symptoms began, Lynd says that her parents have stood by her side unconditionally and fought for her wellbeing.

           “Without them taking me all over looking for answers, I don’t know where I’d be,” she says, adding that her brother is also both her committed supporter and best friend.

    Lynd says her family may not always understand what she is feeling, but they still provide unconditional support in her times of need.

“Even though they tell me they don’t know what I’m going through, they’ve always been there and I know not everybody’s family is like that,” she says. “Just stand by them no matter what.”

    This type of understanding, Lynd says, is critical to maintaining relationships. Due to a frequent lack of this relational aspect, she has lost friends along the way.

           “I don’t go out much with them and they don’t understand why,” Lynd says. “I just don’t want to be in a situation where I’m out and I get a bunch of pains.”

    Social media, on the other hand, has been critical in both maintaining and creating relationships, Lynd says. She fondly lists name of her TN family, other patients whom she’s met across the internet. They even attend each other’s surgeries and their children spend time together.

           “Without the internet, we all wouldn’t have met,” she says.

    The internet has also been pivotal for Lynd because of increased access to research – as opposed to the libraries she used to browse with difficulty at the onset of her symptoms. This is how she first discovered the Facial Pain Research Foundation. Knowing that someone is out there advocating for her, Lynd says, brings great comfort.

“There are really no words to express how thankful you are. I’m so thankful for everything they’re doing,” she says. “I know that they are putting a lot of time and effort and if they only knew how much they’re helping us.”

    Hope is what Lynd hinges her future on, like so many others in her position. For Lynd, it is the key ingredient of daily life and the greatest admonition she would offer to the frightened 18-year-old girl she once was and all the others who find themselves in her shoes.

           “Don’t ever lose hope. I have to believe there’s a cure out there,” she says. “They’re never alone.”