Dr. Ji Published in Special Issue of Science

Ru-Rong Ji, PhDChronic pain is a rising health issue affecting as many as 30 percent of adults, worldwide, with an annual cost of more than $600 billion in the United States alone. Chronic pain after arthritis, nerve injury, cancer, and chemotherapy is typically associated with chronic neuroinflammation. Dr. Ru-Rong Ji, the chief of pain research at Duke Anesthesiology, is featured in a special “Pain Research” issue of the journal, Science, for his work that investigates the role non-neuronal cells play in pain regulation and inflammation.

Dr. Ji is the senior author of the review article, “Pain regulation by non-neuronal cells and inflammation,” published in the journal’s November 14, 2016 issue. Co-investigators include Alexander Chamessian (staff member of Dr. Ji’s Pain Signaling and Plasticity Laboratory) and Yu-Qiu Zhang.

Science JournalAccording to the authors, accumulating evidence suggests that non-neuronal cells such as immune cells, glial cells, keratinocytes, cancer cells, and stem cells play active roles in the pathogenesis and resolution of pain. They studied how non-neuronal cells interact with nociceptive neurons by secreting neuroactive signaling molecules that modulate pain, revealing that “non-neuronal cells can communicate with nociceptive neurons by ‘listening’ and ‘talking’ to neurons.” The authors add that recent studies suggest that bacterial infections regulate pain through direct actions on sensory neurons, and specific receptors are present in nociceptors to detect danger signals from infections. Their study also discusses new, therapeutic strategies to control neuroinflammation for the prevention and treatment of chronic pain.

Dr. Ji is a distinguished professor of anesthesiology at Duke University’s School of Medicine and a faculty member of Duke Anesthesiology’s Center for Translational Pain Medicine where he and other researchers are devoted to understanding the epigenetic processes and signatures of what causes acute pain to become chronic, and reducing the burden of chronic pain by developing innovative, non-opioid pain therapies to improve patient care (highlighted in the cover story of Duke Anesthesiology’s 2016 edition of BluePrint magazine).

Chris KeithDr. Ji Published in Special Issue of Science
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2016 FAER Inductees Announced

Drs. William Maixner and Paul WischmeyerDuke Anesthesiology’s William Maixner, DDS, PhD, and Paul Wischmeyer, MD, have been appointed as members of the Foundation for Anesthesia Education and Research (FAER) Academy of Research Mentors in Anesthesiology.

They received this honor for their contributions as mentors for anesthesia residents, fellows and faculty. The FAER Academy’s objective is to recognize mentors who have not only committed their career to the development and advancement of academic anesthesiologists and others in research, but promoted mentoring among colleagues in the specialty – all in effort to increase the quality of research and advance the scope of academic anesthesiology. The main criterion for membership of the academy is the number of individuals whom the mentor has supported and the quality of work accomplished by those individuals.

Dr. Maixner is a world-renowned pain researcher and the director of Duke Anesthesiology’s newly established Center for Translational Pain Medicine. Dr. Wischmeyer is recognized internationally for his interdisciplinary research and translational approach to challenges in perioperative and critical care medicine. He is the associate vice chair for clinical research and the co-director of the Academic Career Enrichment Scholars (ACES) Resident Research Program within Duke Anesthesiology. Additionally, Dr. Wischmeyer is the director of perioperative research at the Duke Clinical Research Institute (DCRI), the largest clinical research institute in the world.

Chris Keith2016 FAER Inductees Announced
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National Media Features Dr. Jordt Lab Study

Drs . Jordt and Liu

Drs . Jordt and Liu

Duke Anesthesiology’s Drs. Sven-Eric Jordt and Boyi Liu, along with scientists at Zhejiang Chinese Medical University, have discovered a strategy to stop the uncontrollable itch caused by an oily sap, common to poison ivy, poison sumac, poison oak and mango trees.

According to a news release from Duke Health, the research team found that by blocking an immune system protein in the skin with an antibody, they could halt the processes that tell the brain the skin is itchy. The research was done in mice and is described in the November 7, 2016 issue of Proceedings of the National Academy of Sciences.

This cutting-edge research, which could lead to treatments for those allergic to poison ivy (an estimated 80 percent of the population), made national headlines on CBS NewsU.S. News & World Report, HealthDay, STAT, Scientific American, and Univision.

Dr. Jordt is the senior author of the study and director of the Chemical Sensing, Pain and Inflammation Research Laboratory at Duke Anesthesiology. This research was supported with funding from Dr. Liu’s 2015 DREAM Innovation Grant. These grants support innovative high-risk and potentially high-reward investigations to accelerate anesthesia and pain management research – a key component of Duke Anesthesiology’s DREAM Campaign.

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Itch Therapies Study Published in National Academy Journal

Drs . Jordt and LiuScientists at Duke Health and Zhejiang Chinese Medical University have developed a strategy to stop the uncontrollable itch caused by urushiol, the oily sap common to poison ivy, poison sumac, poison oak and even mango trees.

The team found that by blocking an immune system protein in the skin with an antibody, they could halt the processes that tell the brain the skin is itchy. The research was done in mice and is described in the November 7 issue of Proceedings of the National Academy of Sciences. They hope their model could lead to potential treatments for people who are allergic to poison ivy — an estimated 80 percent of the population.

For most people, contact with poisonous plants is painful but not life-threatening. Still, there are significant health care costs associated with more than 10 million people in the U.S. affected each year, said senior author Sven-Eric Jordt, Ph.D., associate professor of anesthesiology at Duke.

“Poison ivy rash is the most common allergic reaction in the U.S., and studies have shown that higher levels of carbon dioxide in the atmosphere are creating a proliferation of poison ivy throughout the U.S. — even in places where it wasn’t growing before,” Jordt said. “When you consider doctor visits, the costs of the drugs that are prescribed and the lost time at work or at school, the societal costs are quite large.”

Some symptoms of the fiery, blistering rash can be alleviated with antihistamines and steroids. But in recent years, scientists have determined that the most severe itching doesn’t go away with antihistamines, because it arises from a different source, Jordt said.

Jordt and collaborators determined the itch is triggered by interleukin 33 (IL-33), a protein in the skin involved in immune response.

All people have IL-33 in their skin, but the protein is elevated in people who have eczema and psoriasis, Jordt said. The protein is known for inducing inflammation, but these new experiments show the protein also acts directly on the nerve fibers in the skin, exciting them and telling the brain that the skin is severely itchy.

A fluorescence microscope image shows the skin of a healthy mouse (left) and skin from a mouse with a poison ivy rash (right). Interleukin-33, shown in green stain, is a protein that acts directly on the nerves, telling the brain the skin is extremely itchy. Sven-Eric Jordt/Duke Health

A fluorescence microscope image shows the skin of a healthy mouse (left) and skin from a mouse with a poison ivy rash (right). Interleukin-33, shown in green stain, is a protein that acts directly on the nerves, telling the brain the skin is extremely itchy. Sven-Eric Jordt/Duke Health

The researchers used an antibody to block IL-33 and found that it not only reduced inflammation, but also cut down scratching in mice with poison ivy rashes. An antibody that counteracts human IL-33 is currently being evaluated in humans through a Phase 1 clinical trial to determine its safety and potential side effects.

In an additional approach tested in the mouse experiments, the researchers also found they could also alleviate itch by blocking a receptor for IL-33, called ST2.

“There could be translational significance here,” Jordt said. “So our next step will be to look at human skin to see if we see the same activity and the same pathways. We will also look at anti-inflammatory drugs that are already approved to see if they have the potential to alleviate itch.”

In addition to Jordt, study authors include Boyi Liu; Yan Tai; Satyanarayana Achanta; Melanie M. Kaelberer; Ana I. Caceres; Xiaomei Shao; and Jianqiao Fang.

The research was supported by the Duke Anesthesiology DREAM Innovation Grant (2015-DIG LIU), Zhejiang Chinese Medical University Start-Up Funding (722223A08301/ 001/004), the National Natural Science Foundation of China (81603676) and three National Institutes of Health — the National Center for Advancing Translational Sciences (UL1 TR001117), the National Institute of Environmental Health Sciences (R01 ES015056, U01 ES015674) and the National Institute of Arthritis and Musculoskeletal and Skin Disease (R21 AR070554). The authors declare no conflicts of interest.

Source: Duke Health News and Communications press release (Durham, N.C. – November 7, 2016).  Jordt is a faculty member of
Duke Anesthesiology’s Center for Translational Pain Medicine and director of the Chemical Sensing, Pain and Inflammation Research Laboratory.

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Director of Orofacial Pain Published in AJO-DO

Aurelio Alonso, DDS, MS, PhDAccurate upper airway measurements can play a pivotal role in identifying patients with breathing or sleep disorders. Duke Anesthesiology’s Aurelio Alonso, DDS, MS, PhD, is a co-author of a newly published study that investigated the differences between cone-beam computed tomography (CBCT) and acoustic reflection (AR) in calculating airway volumes and areas. The manuscript, titled “When static meets dynamic: Comparing cone-beam computed tomography and acoustic reflection for upper airway analysis,” was published in the October 2016 issue of the American Journal of Orthodontics and Dentofacial Orthopedics.   

Subjects with prescribed CBCT images as part of their records were asked to have AR performed. A total of 59 subjects had their five areas of their upper airway measured from CBCT images, acoustic rhinometry and acoustic pharyngometry. Volumes and minimal cross-sectional areas were extracted and compared with software.

According to the authors, results of this study reveal that CBCT is an accurate method for measuring anterior nasal volume, nasal minimal cross-sectional area, pharyngeal volume and pharyngeal minimal cross-sectional area.

Dr. Alonso is the director of orofacial pain for Duke Anesthesiology’s Center for Translational Pain Medicine and notably the first boarded orofacial pain clinician at Duke. This new center further expands the department’s existing clinical and research program in innovative pain therapies by bringing together, under one umbrella, leading basic scientists, clinicians and clinical researchers who have a common core mission of unraveling the causes of painful conditions to better improve patient care. Dr. Alonso is also a pain specialist at Duke Innovative Pain Therapies, a medical pain practice that opened in September of 2016 at Brier Creek in Raleigh. Learn more about this first-of-its-kind pain practice in Duke Anesthesiology’s 2016 edition of BluePrint magazine.

Chris KeithDirector of Orofacial Pain Published in AJO-DO
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Study Shows Menthol Makes Nicotine More Palatable

Sven-Eric Jordt, PhDMenthol, the minty and cooling natural product in peppermint, is a highly popular flavor in tobacco products. More than 30 percent of smokers in the United States smoke menthol cigarettes, and most beginning smokers prefer menthols. Chewing tobacco, snuff and snus also come in highly popular mentholated varieties.

A new study from Dr. Sven-Eric Jordt’s Chemical Sensing, Pain and Inflammation Research Laboratory at Duke Anesthesiology reveals that menthol masks the bad taste of nicotine. Tobacco by itself has a rather unpleasant burnt and bitter taste. This is partially due to nicotine in tobacco that is bitter and irritating, causing a burning and pungent sensation. The manuscript titled, “Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism” is published in the October 2016 issue of the journal Tobacco Control.

“Contributing to Duke Anesthesiology’s pain research efforts, our lab has studied the cooling and soothing effects of menthol that is widely used for topical pain treatment in pain creams and patches,” says Dr. Jordt. “We were intrigued whether menthol would also suppress the irritating effects of nicotine.”

To examine menthol’s effects, Dr. Jordt’s lab scientists presented mice with a choice of water with nicotine or water containing both nicotine and menthol. The mice strongly preferred the mentholated nicotine and did so repeatedly over days. Mice share their aversion to nicotine with humans and also perceive menthol as soothing and cooling, sensing menthol with specific temperature-sensing nerves in the mouth.

“Menthol is not only a pleasant flavor, but has potent sensory effects that make it easier to consume nicotine,” says Dr. Jordt, associate professor in anesthesiology and faculty member of Duke Anesthesiology’s Center for Translational Pain Medicine. “We hope our findings will inform regulatory policies to curtail tobacco use and prevent children from becoming new tobacco consumers.” The study was a collaboration with Dr. Marina Picciotto’s laboratory of the Yale Tobacco Center of Regulatory Science in the Department of Psychiatry, funded by the National Institute on Drug Abuse and the Food and Drug Administration.

Chris KeithStudy Shows Menthol Makes Nicotine More Palatable
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