PainRelief.com Interview with: Matthew Costa Professor of Orthopaedic Trauma Surgery University of Oxford Honorary Consultant Trauma Surgeon John Radcliffe Hospital, Oxford
Dr. Costa
PainRelief.com: What is the background for this study?
Response: The number of patients sustaining a fracture of the hip is increasing rapidly as patients all around the world live into older age. It estimated there will be over 6 million hip fractures by 2050. Approximately half of hip fractures occur at the neck of the thigh bone (femur) and the majority of patients over 60 years with such a fracture are treated with a partial hip replacement in which the head of the femur is replaced with a metal implant (hemiarthroplasty).
There is controversy about how best to fix the hemiarthroplasty implant to the bone of the femur. If the implant is not securely bonded to the patient’s bone it can loosen causing pain and restricting movement and activities of daily living. This study was about the best way to fix the implant to the patient’s bone.
PainRelief.com Interview with: Maaz Siddiqui, BS Department of Medical Education Geisinger Commonwealth School of Medicine Scranton, Pennsylvania
Maaz Siddiqui
PainRelief.com: What is the background for this study?
Response: Over the last twenty years, the rise of deaths due to drug overdoses have been mainly and rightfully attributed to opioids. However, many investigations identify non-opioid drugs and drug classes that additionally contribute to deaths due to polysubstance overdoses. Through the Maine Diversion Alert Program (DAP) data, we examined drugs that often escape the attention of healthcare providers and directly or indirectly contribute to substance misuse, arrests, addiction, and deaths due to overdose.
The goal of this study was to utilize a novel dataset to uncover and identify the noncontrolled drugs that have shown potential to be misused.
PainRelief.com Interview with: Molly Candon, PhD Research Assistant Professor, Center for Mental Health, Department of Psychiatry Assistant Professor, Department of Health Care Management Director, Associate Fellows Program, Leonard Davis Institute of Health Economics Perelman School of Medicine and the Wharton School University of Pennsylvania
Dr. Candon
PainRelief.com: What is the background for this study? What are the main findings?
Response:Insurance design for pain care, including whether treatments are covered and how generously they are covered, is an important element of access and adherence. Acupuncture therapy is a safe and evidence-based treatment for numerous pain conditions, and our team was curious if acupuncture coverage has changed in recent years given the need for non-opioid treatments during the ongoing opioid epidemic.
PainRelief.com Interview with: Juan Ignacio, Teves Agustin, Garcia-Mansilla Italian Hospital of Buenos Aires
PainRelief.com: What is the background for this study?
Response: It is well known that the increased life expectancy of the general population leads to an increase in the number of prosthetic replacement surgeries in the years to come. A concern of patients who consult for this type of procedure is whether age alone is a risk factor for this surgery and the literature is not conclusive about whether age or comorbidities are more important in postoperative results.
For this reason, we decided to compare two series of patients, some older than 80 years and others younger, to determine whether or not age influences the result of total knee replacement.
PainRelief.com Interview with: Matthew S. Panizzon, Ph.D. Associate Professor Department of Psychiatry Center for Behavior Genetics of Aging University of California San Diego
Dr.Panizzon
PainRelief.com: What is the background for this study?
Response: Migraine is a severe neurological disease that affects over 12% of the population. Women are also much more likely to suffer from migraine then men. Despite how common it is, the factors that contribute to migraine are poorly understood.
Professor Kim BennellFAHM Barry Distinguished Professor | NHMRC Leadership Fellow Dame Kate Campbell Fellow Centre for Health Exercise and Sports Medicine Department of Physiotherapy Melbourne School of Health Sciences The University of Melbourne, Victoria Australia
Prof. Bennell
PainRelief.com: What is the background for this study?
Response: Osteoarthritis is a common chronic painful joint condition with no cure that often leads to costly joint replacement surgery. Treatments are needed that can not only reduce symptoms but also slow structural progression of the disease in order to reduce the burden of knee OA. There are no approved disease-modifying treatments available at present.
Platelet-rich plasma (PRP) injections have become a widely used treatment for knee osteoarthritis (OA) in recent years despite the fact that the evidence to support their effects is limited and not of high quality. For this reason, clinical guidelines currently do not recommend PRP for the management of knee osteoarthritis.
To address this gap in knowledge, our study aimed to compare the effectiveness of PRP injections to reduce knee pain and slow loss of medial tibial cartilage volume over a 12-month period. We did this by conducting a clinical trial of 288 people with mild to moderate knee OA. The study included a placebo group where participants were injected with saline into the knee. Participants and the injecting doctors were blind as to whether PRP or saline was injected into the knee.
PainRelief.com Interview with: David M. Dunaief, M.D. Principal Investigator MedicalCompassMD.com
PainRelief.com: What is the background for this study? What are the main findings?
Response: As an internist focusing on dietary intervention, I have been caring for patients with chronic diseases for the past 12 years. Many of my patients have had rapid, marked improvements when they adhere to my LIFE (Low Inflammatory Foods Everyday) diet. The diet, as well as objective evidence that it reduces systemic inflammation (lowers serum C-reactive protein levels), has been described in the peer-reviewed publications:
In addition to improving migraines, the diet has improved symptoms and blood chemistries in patients with high blood pressure, high cholesterol, diabetes, cancer, auto-immune diseases, inflammatory bowel disease, and others. In this case report, we describe a patient who suffered from debilitating migraines for 12.5 years, and who had minimal benefit from avoiding dietary triggers or medications. Within 3 months of adopting the LIFE diet, he was migraine free and remained that way for 7.5 years.
PainRelief.com Interview with: Dr Deanne Jenkin PhD UNSW Australia, now Research Fellow at The Daffodil Centre Sydney, Australia
Dr Jenkin
PainRelief.com: What is the background for this study? What are the main findings?
Response: At the time, long-term opioid use for chronic non-cancer pain was increasing and there were signs that their benefit was overestimated whilst the harms were underestimated. Our randomized trial found that after going home from fracture surgery, strong opioids were not better for pain relief compared to a milder, potentially safer opioid alternative.
PainRelief.com Interview with: Amrita Vijay PhD Division of Rheumatology Orthopedics and Dermatology School of Medicine University of Nottingham Nottingham, UK
Dr. Vijay
PainRelief.com: What is the background for this study? What are the main findings?
Response: We carried out this research as we wanted to see if exercise had an effect on the levels of anti-inflammatory substances produced by gut microbes and on endocannabinoids (i.e cannabis-like substances) produced by our bodies.
One of the key findings of the study is that physical exercise increases levels of the body’s own cannabis-type substances and highlights a key link between how substances produced by our gut microbes interact with these cannabis-like substances and reduces inflammation.
PainRelief.com Interview with: Rajesh Khanna, PhD Professor and Vice Chair of Research, Department of Pharmacology, Associate Director of Research, Comprehensive Pain and Addiction Center University of Arizona
Dr.Rajesh Khanna,
Starting January 2022: Professor, Department of Molecular Pathobiology Director, NYU Pain Center College of Dentistry New York University
PainRelief.com: What is the background for this study?
Response: Chronic pain conditions cause an immense burden on society due to their astonishingly high prevalence and lack of effective treatments. The National Institutes of Health estimates that nearly 100 million people in the United States suffer from chronic pain. Nearly 20-30% of patients prescribed opioids for chronic pain misuse them, according to the National Institute on Drug Abuse. In 2019, nearly 50,000 people in the U.S. died from opioid-involved overdoses and that number increased to nearly 70,000 in 2020. There is clearly an urgent need for non-addictive treatments for chronic pain.
The voltage-gated sodium channel NaV1.7 is preferentially expressed in the peripheral nervous system within ganglia associated with nociceptive pain. This channel modulates the threshold required to fire action potentials in response to stimuli and has been established as a key contributor to chronic pain. Chronic pain states can result from upregulated NaV1.7 expression which has been shown to occur in association with diabetic neuropathy, inflammation, sciatic nerve compression, lumbar disc herniation, and after spared nerve injury. The exact pathways leading to the dysregulation of NaV1.7 are poorly understood, but likely involve mechanisms related to its surface trafficking and regulation via protein-protein interactions.
Our previous work identified the collapsin response mediator protein 2 (CRMP2) as a novel regulator of NaV1.7 function and uncovered the logical coding of CRMP2’s regulatory functions. We found that if CRMP2 is phosphorylated by cyclin dependent kinase 5 at serine 522 and also modified by SUMOylation at lysine 374 by the SUMO conjugating enzyme Ubc9, then NaV1.7 is functional. When not SUMOylated, CRMP2 recruits the endocytic proteins Numb, Nedd4-2, and Eps15, triggering clathrin mediated endocytosis and internalization of NaV1.7. When not at the cell-surface, sodium currents are reduced, alleviating NaV1.7-associated chronic pain. This action of CRMP2 is highly selective for NaV1.7, as no effects on other voltage-gated sodium channel subtypes are observed.
Previous efforts to target NaV1.7 for pain relief have focused on development of direct channel blockers, but this approach has been unsuccessful. Disclosed reasons for failure of these NaV1.7-targeting drugs include issues with: (a) central nervous system penetration, (b) lack of selectivity (e.g., of Biogen’s Vixotrigine), (c) inadequacy of pain models, and (d) insufficient channel blockade.
These factors culminate in continued action potential firing and failure to relieve pain, which has led to skepticism regarding targeting of NaV1.7.
We hypothesized that targeting CRMP2 with a small molecule to prevent it’s SUMOylation would be a novel and effective approach to indirectly regulating NaV1.7 for the treatment of chronic neuropathic pain.
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