A Breath of Fresh Air for Eucalyptus Research

Left to Right: The researchers who work in Dr. Jordt’s lab: Maya Kaelberer, BS; Satya Achanta, DVM, PhD; Dr. Sven-Eric Jordt; Anabel Caceres, PhD; and Boyi Liu, MD

Left to Right: The researchers who work in Dr. Jordt’s lab: Maya Kaelberer, BS; Satya Achanta, DVM, PhD; Dr. Sven-Eric Jordt; Anabel Caceres, PhD; and Boyi Liu, MD

A new study by Dr. Sven-Eric Jordt’s Chemical Sensing, Pain and Inflammation Research Laboratory at Duke Anesthesiology identifies the mechanism through which eucalyptol, the active ingredient in eucalyptus oil, suppresses inflammation.

Eucalyptol, a cooling natural product, is licensed as an over-the-counter treatment in some countries, either as a pill, in lozenges, as an oil for inhalation, or as a cream for pain treatment. Eucalyptol is also found in sage, rosemary and tea tree oil, all used for treatment of inflammation. Clinical trials suggested that eucalyptol is effective as a supportive treatment in bronchitis and chronic obstructive pulmonary disorder, a lung disease caused by smoking. However, eucalyptol’s mechanism of action has remained unclear, and studies in mice and rats required much higher amounts of eucalyptol to be effective than in the human studies.

This study, titled “TRPM8 mediates the anti-inflammatory effects of eucalyptol,” is published in the February 2017 issue of the British Journal of Pharmacology. It identifies a target for eucalyptol and explains why eucalyptol might be more effective in humans.

“We identified TRPM8 as eucalyptol’s target to treat skin and lung inflammation” says Dr. Jordt. “TRPM8 is a sensor for cooling in temperature-sensing nerves in the body. Eucalyptol mimics the sensation of cooling that is known to have anti-inflammatory effects. We also found that TRPM8 in humans is more sensitive to eucalyptol than in the mouse or rat. This may explain why lower amounts of eucalyptol were effective in the published human trials.”

This Duke study provides a rationale for additional human studies testing this widely-used natural product in other inflammatory conditions, and for the development of novel eucalyptol-based drugs. Duke Anesthesiology researchers, Ana Caceres, Boyi Liu, Sairam Jabba and Satya Achanta, contributed to the study. Dr. Jordt is an associate professor in anesthesiology and a faculty member of the department’s newly established Center for Translational Pain Medicine. His research interests focus on the mechanisms that enable humans and animals to sense touch, pain and irritation.

Chris KeithA Breath of Fresh Air for Eucalyptus Research
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Aspiring Physician-Scientist Awarded Prestigious Fellowship

Alexander ChamessianThe Grass Foundation has awarded Alexander Chamessian, an MD/PhD candidate working in the labs of Duke Anesthesiology’s Drs. Ru-Rong Ji and Thomas Van de Ven, a Grass Fellowship for his project, titled “Deciphering Pain and Itch Circuitry in the Spinal Dorsal Horn using Permanent Activity-Dependent Labeling, Electrophysiology, and Single-Cell Transcriptomics.”

The Grass Fellowship Program is the hallmark program of The Grass Foundation which supports research and education in neuroscience. It supports investigator-designed, independent research projects by scientists early in their careers. Thanks to this award, Chamessian will spend 14 weeks this summer at Woods Hole working on his project.

Chamessian’s research focuses on understanding the molecular and cellular mechanisms of nociception, with an emphasis on chronic pain. He is currently pursuing his PhD jointly with Dr. Ji in the Pain Signaling and Sensory Plasticity Laboratory and Dr. Van de Ven in the Nerve Injury and Pain Mechanism Laboratory. Both labs are part of Duke Anesthesiology’s Center for Translational Pain Medicine which represents a novel entity that is transforming the way painful conditions are diagnosed and treated.

Chris KeithAspiring Physician-Scientist Awarded Prestigious Fellowship
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Acupuncture Proves to be Integrative Therapy for Bell’s Palsy

Jongbae Jay Park, PhD, LAcBell’s palsy is a nerve disorder that causes sudden paralysis of unilateral facial muscles. Studies show that 70 percent of those affected will completely recover, but 15 percent will go on to experience permanent damage. This prolonged paralysis and asymmetry can affect psychological and social behaviors which can undermine patients’ quality of life.

Duke Anesthesiology’s Dr. Jongbae Jay Park is a co-author of a newly published study in the February 2017 issue of Complementary Therapies in Clinical Practice, titled “A close look at an integrative treatment package for Bell’s palsy in Korea.”

As the study notes, Bell’s palsy patients experience significantly higher degrees of distress and report that they feel helpless when doctors don’t acknowledge problems other than facial disfigurement. While clinical guidelines in conventional medicine don’t yet recommend acupuncture treatment for Bell’s palsy due to poor study design and reporting, acupuncture is one of the most sought after treatments for this condition in many Asian countries.

The authors conclude that the lack of awareness, dearth of knowledge in patient needs, and shortage of treatment options available during the recuperation months increase the need and significance of an integrative treatment program for a well-rounded overall recovery. While rigorous research is warranted, they highly suggest that it is worth applying integrative medicine, such as acupuncture, to Bell’s palsy patients.

Dr. Park is the director of acupuncture and Asian medicine for Duke Anesthesiology’s Center for Translational Pain Medicine and a pain specialist at Duke Innovative Pain Therapies, located in Raleigh, North Carolina. Learn more about this first-of-its-kind pain practice in Duke Anesthesiology’s 2016 edition of BluePrint magazine.

Chris KeithAcupuncture Proves to be Integrative Therapy for Bell’s Palsy
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Dr. Terrando Awarded Core Specific Voucher

Niccolo Terrando, PhDDuke University’s Mouse Behavioral and Neuroendocrine Core Facility has awarded Duke Anesthesiology’s Niccolo Terrando, PhD, a $5,000 voucher to evaluate the effects of vagal nerve stimulation on cognitive function.

His project, titled “Vagal Nerve Stimulation as a Therapy for Postoperative Cognitive Dysfunction,” will analyze the efficacy in protecting or ameliorating cognitive decline after surgery using this novel intervention. This project relates to the 2016-2017 funded Duke Institute for Brain Sciences Research Incubator Award, titled “Bioelectronic Medicine and Cholinergic Regulation of Postoperative Cognitive Dysfunction.”

Dr. Terrando is the director of the department’s Neuroinflammation and Cognitive Outcomes Laboratory and a collaborator with the Center for Translational Pain Medicine which represents a novel entity aimed at driving the discovery of new and innovative pain therapies to improve patient outcomes.

Chris KeithDr. Terrando Awarded Core Specific Voucher
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Dr. Ji’s Lab Makes Local Headlines for Autism-Pain Discovery

Ru-Rong Ji, PhDAbnormal pain sensitivity is often associated with autism spectrum disorders which can affect the quality of life of those individuals. New research from two Duke University labs, Dr. Ru-Rong Ji’s Pain Signaling and Plasticity Laboratory and Dr. Yong-Hui Jiang’s autism research lab, reveals a potential mechanism underlying pain insensitivity in autism. According to an article published by Duke Today on December 1 titled, “Autism-Linked Protein Crucial for Feeling Pain,” this finding is the first to connect autism to one of the most well-studied pain receptors, TRPV1 (transient receptor potential ion channel subtype V1).

This research was published in the December 2016 issue of the journal, Neuron, in an article titled, “SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons.” The manuscript describes how SHANK3 (a prominent autism gene), expressed by peripheral primary sensory neurons, regulates TRPV1 function and heat hyperalgesia after inflammation and nerve injury, offering a mechanistic insight into pain dysregulation in autism. The co-first authors of this paper are Qingjian Han, PhD, Yong-Ho Kim, PhD (both with Dr. Ji’s lab), and Xiaoming Wang, PhD. Co-investigators with Duke Anesthesiology include Dr. Ji, Zhi-Jun Zhang, Di Liu, Mark Lay, Wonseok Chang, Temugin Berta and Yan Zhang.

As explained in the Duke Today article, Dr. Ji’s lab put SHANK3-dificient mice through several sensory tests which found that animals had lower sensitivity than normal mice to heat and heat-related pain, similar to that of a sunburn. Their research found 1) that not only is the SHANK3 protein present in the brain, but also in a cluster of pain-sensing neurons called the dorsal root ganglion in mice, 2) SHANK3 in the same types of cells from human donors who did not have autism, 3) that SHANK3 is expressed on the sending sides of the synapse. Dr. Ji was surprised to find that SHANK3 is expressed in the peripheral nervous system and notes that this is the first study where researchers looked for it outside of the brain – a study that could shape how effective treatments for autism are developed.

Co-expression of SHANK3 (red) and TRPV1 (green) in primary sensory neurons in mouse dorsal root ganglion in the peripheral nervous system.

Co-expression of SHANK3 (red) and TRPV1 (green) in primary sensory neurons in mouse dorsal root ganglion in the peripheral nervous system.

Dr. Ji is the chief of pain research at Duke Anesthesiology, a distinguished professor of anesthesiology in the Duke University School of Medicine, a faculty member of Duke Anesthesiology’s Center for Translational Pain Medicine, and a member of the Duke Institute for Brain Sciences. His lab focuses on identifying molecular and cellular mechanisms that underlie the genesis of chronic pain and developing novel pain therapies that can target those mechanisms.

Chris KeithDr. Ji’s Lab Makes Local Headlines for Autism-Pain Discovery
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Dr. Maixner Makes National Headlines About Surgeon General’s Report

William Maixner, DDS, PhDThe surgeon general released a landmark report about drug addiction and abuse on November 17 which prompted both praise and critique from pain specialists across the nation, including a world-renowned pain researcher with Duke Anesthesiology, Dr. Bill Maixner.

According to an article by Duke Today and an interview posted on YouTube by Duke Health, he commends the report for outlining ways to deal with an overt problem around addiction and substance abuse, and providing full recognition that this is a disease rather than a character flaw. But he adds that it missed an opportunity to call for research and development of additional medical alternatives to opiates for pain management.

The report serves as a call to action and tackles what Dr. Maixner calls “the hidden epidemic” of chronic pain in America which affects more than 100 million adults and costs society more than $635 billion each year. “The cost of treating chronic pain is greater than the combined costs of diabetes, cancer and heart disease,” notes Dr. Maixner. “Yet we spend just four cents per pain patient annually on research, while pain patients consume about 15 percent of health care costs annually. That’s a big imbalance.”

Dr. Maixner was also featured in an NBC News article about the report, which he believes could have gone even further. He says, “There’s very little language regarding the need for discovery of new treatments, discovery of new therapies for chronic pain — which is another epidemic. One of the reasons we have this hidden epidemic in chronic pain is the fact that we don’t have good therapies, and many physicians rely on the use of opioids.” He adds, “We find, unfortunately, that a large number of these individuals are treated by opioids by well-intended individuals who have very little option but opioids to go to.”

Following the release of the surgeon general’s report, MedPage Today formed a panel of experts in addiction, pain and emergency medicine (including Dr. Maixner) to begin a national dialogue about the crisis of addiction. Click here to watch the panel discussion.

As highlighted earlier this year in the cover story of Duke Anesthesiology’s annual magazine, BluePrint, Dr. Maixner says one-tenth of chronic pain patients are suffering from opioid addiction and abuse due to excessive exposure to opioids which are often misappropriated. He believes the only way to deal with the abuse and addiction is to discover new medications and innovative pain therapies which require research.

Dr. Maixner is the director of Duke Anesthesiology’s Center for Translational Pain Medicine. This 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. He also played a key role in the opening of a first-of-its-kind pain practice, Duke Innovative Pain Therapies, located in Raleigh.

Chris KeithDr. Maixner Makes National Headlines About Surgeon General’s Report
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