Neuron Nate Nathan Thomas Fried
Unraveling the central pathways behind chronic pain


Neuroscientist, Writer, Science Advocate, Educator, Web Designer & Developer

Jan 23, 2018

April 25, 2018

Welcome! My name is Dr. Nathan Fried (or, just Nate). I'm a postdoctoral fellow at the University of Pennsylvania's Department of Neuroscience in Philadelphia working with Dr. Wenqin Luo to unravel how the brain changes in patients who develop chronic trigeminal pain. This work is currently supported by an IRACDA K12 PENN-PORT Postdoctoral Fellowship.

I obtained my PhD in Neuroscience at Thomas Jefferson University under Dr. Michael Oshinsky and Dr. Melanie Elliott where I studied migraine. I received my BS in Biology and Mathematics while researching Alzheimer's Disease under Dr. Aleister Saunders at Drexel University. I have presented my work world-wide and have published in numerous peer-reviewed journals. I was a New Headache Investigator Research Tournament Winner, an International Headache Academy Trainee, and a North American Pain School Trainee. I had the immense honor of serving as a T32 Mentoring Jr. Investigators in Alcohol Research Fellow from 2012-2015 and as a Leopold Schepp Foundation Grantee from 2007-2011. I am forever thankful to have had the amazing opportunity to work with the greatest minds in pain research.

My interests in neuroscience first began at Drexel where I studied Alzheimer's Disease; a disorder that is not only deadly, but also robs you of the essence of who you are - memory. This interest in science and the mind grew to other forms of scientific expression as I explored scientific writing, science outreach, acting, and graphic design/web development where I founded the freelance collective, CafeGuyDesigns. This fascination with the brain and the human experience eventually brought me to the doorstep of Jefferson, where I entered a PhD program in Neuroscience. During this time, my interest in memory evolved into one of sensory systems. If memories represent "who we are as people", then our senses are the fundamental neurological conduit to "how we become who we are" since these systems allow us to experience and interpret the world around us. One of these sensory modalities is pain - a warning system that is vital to survival. This led me to migraine where I developed a thesis investigating the neurochemical mechanisms behind the hangover headache. Although this seems like an odd thing to study for five years, alcohol is a very common trigger for migraine attacks. If we can understand how a particular trigger works to cause pain, no matter how inconsequential it may seem, we can find the physiological or neurochemical "weakness" that allows it to cause a migraine attack. Once we find that weakness, we can target it for treatment. Since completing my thesis, I have joined the ranks of the University of Pennsylvania as a postdoctoral fellow continuing my research on pain.

I am a passionate researcher with a great interest in public outreach in the sciences. I have invited congressmen to our labs as part of Capital Hill Day and written for numerous scientific audiences while contributing to the Philadelphia Science Festival. As a PENN-PORT fellow, I'm learning to balance research with teaching as a professor at multiple institutions throughout the Philadelphia region while focusing to increase underrepresented groups in the biomedical sciences. I was the VP of career development for the Jefferson GSA and a founding member of Jefferson Bizbio, which advocated for more opportunities and education in the business side of science. As the son of a watchmaker father and school-teacher mother from Riverside, NJ in a lower-income setting, I understand how hard it is for individuals from lower socioeconomic backgrounds to go through the long-haul of scientific training. If there is ever anything I can do to help, feel free to connect with me below. I'm available for special lectures at all levels, advice, or just help with fascinating ideas. Never hesitate to reach out.

Fried NT "Migraine, Pain, and What the Government Is Doing to Help: A Conversation with Michael Oshinsky" | Michael Oshinsky discusses migraine, pain, and NIH’s efforts to help scientists find new treatments for these disorders. | RELIEF 28Jan2018.

Fried NT "Designing Safer Opioids: How Biased Are You?" | A systematic analysis of multiple mu opioid receptor agonists reveals that bias factor correlates with therapeutic window | Pain Research Forum 11Jan2018.

Fried NT "OUCH! Quit Pulling My Hair!" | Scientists discover pain neurons in mice that are activated in response to painful pulling of even a single hair | RELIEF 20Nov2017.

Fried NT "Newly Identified Nociceptors Transmit Pain From Hair Follicles" | A-delta nociceptor population responds to pulling of even a single hair in a mouse study | Pain Research Forum 10Oct2017.

Fried NT "Phosphorylation Outside the Cell: A New Factor in Chronic Pain?" | Extracellular phosphorylation of a single tyrosine in EphB2 on spinal cord neurons increases NMDAR activity and pain | Pain Research Forum 15Sep2017.

Fried NT "Outside or Inside? If at First You Don’t Succeed (with a New Pain Drug), Try, Try Again" | A new discovery suggests researchers could again set their sights on substance P, a molecule with a known role in pain. | RELIEF 24Aug2017.

Fried NT "A New Way To Measure Pain in Infants" | A simple electroencephalogram recording provides an objective measure of pain in infants. | RELIEF 1Aug2017.

Fried NT "Consider the Endosome: New Life for Neurokinin 1 Receptor Antagonists?" | Blocking substance P activation of NK1R in endosomes is more effective at relieving pain than cell surface inhibition, but questions remain | Pain Research Forum 18Jul2017.

Fried NT "Uncovering the Genetic Links Between Pain and Depression" | A recent study lays the groundwork to understand the genetic basis for the pain-depression connection. | RELIEF 5Jul2017.

Fried NT "Redesigning an Old Opioid to Make a Safer Drug" | Computer simulation aids redesign of fentanyl so it works only in injured areas, avoiding unwanted side effects. | RELIEF 17Jun2017.

Fried NT "A New Brain Measure of Nociception in Infants" | EEG recordings reveal noxious-evoked brain activity that can serve as an objective measure of pain and analgesic efficacy | Pain Research Forum 12Jun2017.

Fried NT "Can Old Drugs Be Repurposed to Prevent Morphine Withdrawal? " | Findings in rodents suggest a path to helping patients. | RELIEF 23May2017.

Fried NT "Long-Term Neuropathic Pain Leads to Changes in Gene Expression in Brain Areas Associated With Depression" | RNA sequencing in multiple connected brain regions identifies large number of genes underlying pain-depression connection; new study will serve as resource for future work | Pain Research Forum 19Apr2017.

Fried NT "A New Opioid Targets Active Sites of Inflammation to Relieve Pain." | NFEPP binds and activates mu-opioid receptors only at low pH, soothing pain in rats without typical side effects| Pain Research Forum 23Mar2017.

Fried NT "Inhibition of Pannexin-1 Channels on Microglia Reduces Morphine Withdrawal in Rodents" | Findings point the way toward a clinical strategy to mitigate an adverse effect of opioids | Pain Research Forum 21Feb2017.

Fried NT "An Autism Gene Regulates Pain Too" | The autism gene, called SHANK3, affects a well-known protein that transmits pain signals. | RELIEF 14Feb2017.

Fried NT "Can Pain Be Transferred Through Scent?" | Findings in mice provide a new explanation for the “social transfer” of pain. | RELIEF 1Feb2017.

Fried NT "Autism Gene Modulates Thermal Pain" | SHANK3, a gene closely associated with autism spectrum disorders, regulates TRPV1 function, possibly contributing to changes in pain sensitivity seen in autism | Pain Research Forum 4Jan2017.

Fried NT "Olfactory Cues Facilitate the Social Transfer of Pain in Mice " | Control animals housed in same room but different cage as experimental animals experience pain hypersensitivity | Pain Research Forum 9Nov2016.

Fried NT "Is It Time to Deprioritize Preclinical Pain Research?" | At the North American Pain School, trainees debated the pros and cons of the issue | Pain Research Forum 13Sep2016.

Fried NT "From Wishful Marine Biologist to Pain Neurobiologist: A Conversation With Robert Gereau" | Pain Research Forum 6Sep2016.
Fried NT, Elliot MB, Oshinsky ML. "The Role of Adenosine Signaling in Headache: a Review." Brain Sci. The Pathogenesis and Treatment of Headache Disorders special issue 2017, 7(3), 30.

Fried NT, Maxwell CR, Elliot MB, Oshinsky ML. "Region-specific disruption of the blood-brain barrier following repeated inflammatory dural stimulation in a rat model of chronic trigeminal allodynia." Cephalalgia 2017.

Fried NT, Moffat C, Seifert EL, Oshinsky ML. "Functional Mitochondrial Analysis in Acute Brain Sections from Adult Rats Reveals Mitochondrial Dysfunction in a Rat Model of Migraine." Am J Physiol Cell Physiol 2014, 307(11):C1017-30.

Talati PG, Hoang DT, Fried NT, Magee MS, Fineberg JD. "A Perspective on PhD Career Outlook: Training, Mentoring and Utilizing a New Generation of STEM Doctoral Degrees." Technology Transfer and Entrepreneurship 2014, 1(2):138-143.

Hirata H, Fried NT, Oshinsky ML. "Quantitative characterization reveals three types of dry-sensitive corneal afferents: pattern of discharge, receptive field, thermal and chemical sensitivity." Journal of Neurophysiology 2012, 108(9):2481-93.
Fried NT. “How your brain perceives time.” September 2017, TimeCamp101, Icebox Project Space at the Crane Arts, Philadelphia, PA.

Fried NT. “Synesthesia, LSD, and the rewiring of our senses.” April 2017, Sensory Overload, Philadelphia Science Festival, Yard’s Brewery, Drexel University, Philadelphia, PA.

Fried NT. “Social Media & Science.” April 2017, Communicating Your Science Conference, Drexel University, Philadelphia, PA.

Fried NT. “Pain, beer, and that darn hangover headache.” Jan 2017, Washington Township High School, Washington Township, NJ.

Fried NT, Abdus-Saboor I, Luo W. “Using light to dissect peripheral circuits of chronic pain.” Feb 2017, Rutgers University Dept. of Biology Seminar Series, Camden, NJ.

Fried NT. “Differentiating the effects isometheptene isomers to decrease trigeminal sensitivity in a rat model of primary headache.” June 2015, Tonix Pharmaceuticals Expert Meeting, Washington, DC.

Fried NT. “Isometheptene: It works, but for the wrong reason.” June 2015, American Headache Society Annual Meeting, Washington, DC.

Fried NT. “Unraveling basic migraine physiology by defining how alcohol affects trigeminal pain.” May 2015, University of Texas at Austin.

Fried NT. “Mitochondrial Dysfunction in Migraine: New Insights into Potential Therapeutic Targets.” March 2014, Thomas Jefferson University Headache Center Clinicians Meeting, Philadelphia, PA.
Fried NT, Oshinsky ML. “The (R)- isomer of isometheptene, decreases trigeminal sensitivity in a rat model of primary headache.” June 2016 American Headache Society Annual Scientific Meeting, San Diego, CA.

Hann S, Fried NT, Venkatesan L, Oshinsky ML. “Effectiveness of 'Burst' Occipital Nerve Stimulation in Treating Allodynia in a Rodent Model of Migraine.” December 2015 The North American Neuromodulation Society Annual Meeting, Las Vegas, NV.

Hirata H, Fried NT, Oshinsky ML. "Short exposure to intense tear hyperosmolarity leads to functional alterations of the corneal nerves involved in tearing and/or ocular pain: Implications for dry eye disease." March 2013 The Association for Research in Vision and Ophthalmology Annual, Meeting Seattle, WA

Khandelwal P, Schuster J, Fried NT, D'Cruz T, Lee J, Saunders A. "Identification Of Regulators Of APP Metabolism On Chromosome 10" July 2008 International Conference on Alzheimer's Disease, Chicago, IL

Reddy M, Wong J, Fried NT, Prabhakar U . "Human IL-12/23 mAb inhibits Cutaneous Lymphocyte Antigen, IL-12R, and IL-2Ra expression on activated peripheral blood T lymphocytes and secretion of IFN- y, IL-17, IL-2, IL-10, and TNF-a cytokines" April 2006, Society for Investigative Dermatology, Philadelphia, PA
Have a question about my work? ...a general inquiry about the brain? ...something you don't quite understand in your own studies?
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Topic: Trigeminal Pain
University: University of Pennsylvania
Position: Postdoctoral Fellow
Mentor: Wenqin Luo, PhD
The Story:

The trigeminal system appears to be particularly sensitive to multiple forms of chronic pain that are incredibly common: migraine, TMD, chronic tooth pain, chronic dry eye pain, burning mouth syndrome, and many others. At the University of Pennsylvania, I am combining modern neuroscience techniques, such as optogenetics and viral tract tracing, with the power of immediate early gene (IEG) expression to control, manipulate, and identify what makes the trigeminal system so unique in terms of pain. Furthermore, we are delving deep into the brain to identify and characterize the unique pain circuits that underlie the psychiatric components of pain. By performing this research, we hope to provide a greater understanding of pain from a biopsychosocial perspective with an eye at identifying novel therapeutic targets.


Topic: Chronic Migraine
University: Thomas Jefferson University
Position: PhD Candidate
Mentor: Michael Oshinsky, PhD
Melanie Elliott, PhD
The Story:

Migraine affects 36 million individuals in the US, costing upwards of $30 million every year in lost work, medication, and doctor visits. It was recently ranked by the World Health Organization as the 3rd most prevalent neurological disorder on the planet. It's important to note that this is not JUST a simple headache. This is a full neurological disorder that affects multiple parts of the brain and can lead to many other symptoms such as nausea, vomiting, sensitivity to light and sound. For a large subset of these patients, they actually experience chronic migraine which is described as migraine pain that occurs more often than not (ie, >15 days/month). Think back to your college days and your worst hangover headache ever experienced. Now imagine having that headache all the time- at work, with your family, while in bed.

For many of these patients, popping an ibuprofen or aspirin does nothing to help. Even migraine-specific drugs do not work to relieve this pain. The limited treatment options force some to even undergo invasive surgery where they have a nerve stimulator implanted under the skin of their face as it is the only effective treatment to prevent this pain. A related form of headache called cluster headache has even been nicknamed as the "suicide headache" as the pain experienced by these patients has caused some to go to such lengths to relieve the pain. A video of a patient experiencing this form of pain can be found on youtube, but it is not an easy video to watch.

Dr. Michael Oshinsky, a leading neuroscientist currently at the NIH, along with the Jefferson Headache Center and Dr. Melanie Elliott are investigating the neurological mechanisms behind migraine to find better treatment options. Under their mentorship, I worked on several different projects that used a rat model of trigeminal pain with migraine-like features. These animals would actually experience bouts of head pain that were very similar to the headaches experienced by patients. With the use of these animals, we are able to study the neurological systems responsible for transmitting headache pain to identify novel therapeutic targets.

A key to identifying critical brain regions and molecular pathways that are changed in migraine patients is by studying how migraine triggers, substances or occurrences that "trigger" a headache, work in these rats. If we can identify the mechanisms behind their ability to induce pain, we can hone in on these keys areas or molecular pathways. Although it sounds odd, my research focused on how alcohol can initiate trigeminal pain (aka the hangover headache). In doing so, we found a critical neurotransmitter system that has been overlooked in migraine and a novel mitochondrial dysfunction that promotes this neurotransmitter's effect on pain. With this information, we may be on the brink of finding several new treatment options for patients who experience this debilitating form of pain.

Topic: Alzheimer's Disease
University: Drexel University
Position: Undergraduate Researcher
Mentor: Aleister Saunders, PhD
The Story:

Alzheimer's disease (AD) is a devastating disorder that is becoming incredibly important to tackle immediately because of the aging baby boomers who are at high risk of developing this disease. Unlike many other ailments, Alzheimer's disease steals not just your health, but also your memory which is arguably the essence of who you are as a human being. If we do not find a cure, it is expected that this disease will end up costing us over $1.1 TRILLION by 2050. This is nearly as expensive as the war with Iraq.

The current avenue of tackling this issue is with preventative treatment to delay the onset of the disease. Since damage begins long before you see the symptoms, the key to this strategy is early diagnosis. Dr. Aleister Saunders developed a very interesting way to identify the genes that can affect the protein (Abeta) that is thought to be key to the development of AD. He does this with a neuronal cell line that can report the amount of this protein within the cell by illuminating light. More light, more Abeta. Less light, less Abeta. This reporter construct allows him to turn on and off specific genes one by one with the use of RNAi technologies and ask whether that gene increases or decreases the amount of light emitted by these neurons, and thus, the amount of the Abeta protein present. Once he finds the many genes that can modulate Abeta levels, he can perform further research to understand the function of that gene and if it could be used as a therapeutic target to modulate Abeta and treat AD.

My work with Dr. Saunders was to investigate a specific group of genes called histone deacetylases (HDACS). These genes can be considered a master regulator within the cell since they directly control the expression of many other genes. In fact, targeting HDACS has shown to be an effective means to treat many other neurological disorders. By identifying genes that can specifically modulate Abeta levels, we can come closer to understanding the complexities of Alzheimer's Disease to one day find a preventative therapy or maybe even a cure to restore what was once thought to be lost.

"What’s Behind the Spatial Acuity for Pain?" | Pain Research Forum 14Dec2017.

" Crane Arts exhibit explores ‘time and temporality’." | The Temple News 4Oct2017.

"How Drexel Scientists are Communicating their Research." | Drexel News Blog 19Apr2017.

"Penn Medicine Poised for Strong Showing at 7th Philly Science Festival." | Penn Medicine News 5Apr2017.

"WTHS AP psychology students learn about brain pain." |, True NJ 7Feb2017.

"WTHS students get to know the brain." | The Washington Township Sun 20Jan2017.

"In Search of a Cure for the Dreaded Hangover." | Scientific American 17Mar2014.

"Hangover Headache." | The Scientist 1May2011.

"Science Has Found the Best Way to Cure Your Hangover." | GAWKER 18Jan2011.

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