Neuropathy: Repeated High Concentration Capsaicin Patches Provided Back Pain Relief and Reduced Need for Opioids Interview with:
Kai-Uwe Kern MD, PhD
Institute of Pain Medicine/Pain Practice
Wiesbaden, Germany What is the background for this study?

Response: In recent studies a progressive response to high-concentration capsaicin patch (HCCP) with repeated treatment was observed, meaning that patients with insufficient pain relief after the first application of HCCP, still may respond to a second, third, or even fourth application. Based on these latest findings, and also on my personal clinical experience, we aimed to systematically analyse the pool of patients in my Pain Practice with at least two HCCP treatments.

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Multiple Sclerosis: Widespread Pain with Nociplastic Features (WPNF) Linked to Low Physical Activity Interview with:
Libak Abou PhD, MPT
Department of Physical Medicine & Rehabilitation
Michigan Medicine
Institute for Healthcare Policy and Innovation
University of Michigan, Ann Arbor, Michigan What is the background for this study?

Response: Chronic pain is a common symptom experienced by persons with multiple sclerosis (MS) that affects their daily living functioning including physical activity. Growing evidence indicates that persons with MS may experience various types of chronic pain including widespread pain with nociplastic features (WPNF), nociceptive pain, and/or neuropathic pain. WPNF is a chronic and diffuse pain which can be challenging to localize or describe precisely. In person with multiple sclerosis, this type of pain arises from altered processing signals within the central nervous system. This is opposed to pain that arises from specific tissue damage, classified as nociceptive pain, or pain related to demyelination and axonal damage, classified as neuropathic pain.

Our main goal with this study was to investigate whether differences exists on the level of physical activity achieved by persons with MS based on the type of chronic pain they experience

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Key Driver of Neuropathic Pain Identified by Baylor College of Medicine Scientists Interview with:
Kimberley Tolias, Ph.D.
Department of Neuroscience
Biochemistry & Molecular Biology
Baylor College of Medicine
Houston, TX 77030 What is the background for this study?

Response: Neuropathic pain is a chronic pain condition that affects millions of people worldwide, significantly impairing their quality of life.  Symptoms of neuropathic pain include spontaneous shooting or burning pain, pain from activities that don’t normally cause pain (allodynia), and heightened pain sensitivity (hyperalgesia).  Current treatment options for neuropathic pain, such as opioids, focus on symptom suppression and are generally ineffective and often cause unwanted side effect.  In order to develop safer, more effective chronic pain treatments, we need to better understand the processes that lead to neuropathic pain.

Neuropathic pain is caused by nerve damage from a variety of insults (e.g., injury, disease, infection, chemotherapy drugs), which trigger structural and functional changes in the neurons and synaptic connections that transmit pain signals.  These activity-dependent alterations in somatosensory neural circuits are thought to be responsible for the persistent symptoms associated with chronic pain, but how they are induced and maintained following nerve injury or disease remains unclear.  To address this problem, our research team, including lead and co-corresponding author Dr. Lingyong Li (now at University of Alabama at Birmingham), investigated the mechanisms that underlie neuropathic pain, with the goal of identifying strategies to prevent or control it.

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COVID Effects on Nerves May Lead to Better Pain Relief Medications Interview with:
Venetia Zachariou PhD
Edward Avedisian Professor
Chair of Pharmacology, Physiology & Biophysics
Boston University Chobanian & Avedisian School of Medicine What is the background for this study?

Response: COVID-19, the disease resulting from SARS-CoV-2 infection, is associated with highly variable clinical outcomes that range from asymptomatic disease to death. For those with milder infections, COVID-19 can produce respiratory infection symptoms (cough, congestion, fever)  as well as loss of the sense of smell.

A substantial number of actively infected patients suffering from both mild and severe infections experience sensory-related symptoms, such as headache, visceral pain, Guillain-Barre syndrome (GBS), nerve pain and inflammation. In most patients these symptoms subside after the infection ends, but, for other patients, they can persist. 

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UTHealth SA Researchers Study Link Between Omega Fatty Acids and Peripheral Neuropathy Interview with:
Ken M. Hargreaves, DDS, PhD

Professor and Chair
Department of Endodontics
The University of Texas Health Science Center at San Antonio

Dr. Hargreaves What is the background for this study? What are the main findings?

  1. About ten years ago our lab found that the omega-6 lipids can generate pain-producing lipids by activating the capsaicin (found in red hot chili) receptor. At about that time, other scientists reported that a related lipid, the omega-3, can generate pain-relieving lipids. 
  2. Scientists have known for a long time that both omega-6 and omega-3 lipids are “essential fatty acids”, meaning that our body does not make them so they must come in our diet.
  3. So, we tested the idea that a high omega-6 diet would be a risk factor for pain. That is exactly what we found: mice fed a high omega-6 diet had greater pain-like responses after inflammatory or neuropathic injury.
  4. Mice with diabetic neuropathy actually had worsening of symptoms after a high-6 diet. Importantly, this was largely reversed in mice fed a high omega-3 diet.
  5. We also found a drug that blocked the release of the omega-6 lipids from cell membranes and this drug significantly reduced diabetic neuropathy pain in mice.
  6. We then transitioned to clinical research.  We collected ankle skin biopsies from participants with type II diabetic neuropathy and from age- and sex-matched controls.  The tissue levels of omega-6 lipids predicted pain levels, with higher omega-6 lipids associated with higher reports of pain. What should readers take away from your report?

  1. Dietary recommendations have been made for patients with many disorders such as cardiovascular disease, diabetes and autoimmune disease.  Our findings suggest that pain should be added to this list and that a diet enriched with a higher ratio of omega-3 to omega-6 lipids may help to reduce pain.
  2. Examples of foods with a high omega 3:6 ratio are tune (25:1 of omega 3:6), broccoli (6:1), flax seeds (4:1), mango (3:1), spinach (5:1) and lettuce (2:1).  Examples of foods with excessive omega-6:3 would include many processed foods cooked in vegetable oils such as French fries, hamburgers and the like. What recommendations do you have for future research as a result of this study?

ResponseOur study has identified several paths for future research including a clinical trial evaluating the effects of a high omega 3:6 diet on pain, development of new drugs to block omega-6 release and the possible development of lipids as a biomarker for pain.

No disclosures.  


Boyd, J.T., LoCoco, P.M., Furr, A.R. et al. Elevated dietary ω-6 polyunsaturated fatty acids induce reversible peripheral nerve dysfunction that exacerbates comorbid pain conditions. Nat Metab 3, 762–773 (2021).

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Diabetic Neuropathy: High-Frequency Spinal Cord Stimulation Offers Pain Relief Interview with:
Erika A. Petersen, MD, FAANS, FACS
Professor of Neurosurgery
Residency Program Director
UAMS Department of Neurosurgery What is the background for this study?

Response: Painful diabetic neuropathy is a common occurrence for patients with diabetes and can have a tremendous negative impact on their quality of life. Currently, the best available treatments include several types of medications and topical solutions, but there are many patients who do not achieve adequate pain relief or cannot tolerate side effects from these treatments. We need new options for patients who have tried the recommended first- and second-line treatments but still suffer with severe pain.

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Non-Viral Gene Therapy Offers Hope for Pain Relief from Diabetic Neuropathy Interview with:  
Sheila Yi, Helixmith What is the background for this study? Would you explain how VM202 is unique?

  • ResponseDiabetic peripheral neuropathy is one of the most common complications of diabetes and many of DPN patients suffer from severe pain that affects their daily activities and life quality. Though there are medications, both Rx and OTC drugs, used to ameliorate pains from diabetic peripheral neuropathy, many of them fall short of analgesic efficacy or often lead to not so trivial side effects. 
  • Engensis (VM202) is plasmid DNA therapy, non-viral gene therapy, which encodes hepatocyte growth factor (HGF) gene that is designed to simultaneously express two isoforms of HGF protein at high levels. HGF is known to have angiogenic and neurotrophic effects and, when expressed in the human body, induces formation of new micro vessels and nerve regeneration through remyelination and axon outgrowth, resulting in improvement in peripheral neuropathy condition. Engensis does not integrate into the human genome.
  • Historically, our research first focused on therapeutic angiogenesis of HGF with a proof of concept research in critical limb ischemia, an extreme form of peripheral artery disease. In the process, we realized that Engensis would also be effective for peripheral neuropathy, and a coffee chat with the current PI, Dr. Kessler of Northwestern University, led to an idea of using Engensis in neurological diseases.
  • Throughout Phase 1 through 3 clinical trials for DPN in the US, Engensis has been observed safe and well-tolerated in patients, and, during the Phase 3 study, received RMAT (regenerative medicine advanced therapy) designation from the FDA.
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