Ms Emma Ho | BAppSc(Phty)(Hons), PhD Candidate The University of Sydney Faculty of Medicine and Health | Charles Perkins Centre Musculoskeletal Research Hub | Sydney NeuroMusculoskeletal Research Collaborative Faculty of Medicine and Health, The Back Pain Research Team, Sydney Musculoskeletal Health, The Kolling Institute, School of Health Sciences
Emma Ho
PainRelief.com: What is the background for this study?
Response: Adults with chronic low back pain (lasting for more than 12 weeks) not only experience physical disability but can also suffer psychological distress in the form of anxiety, depression, and fear avoidance (avoiding movement for fear of pain).
Clinical guidelines therefore consistently recommend a combination of exercise and psychosocial therapies for managing chronic low back pain. However, not much is known about the different types of psychological therapies available as well as their comparative effectiveness and safety, leaving doctors and patients often unclear about the best choice of treatment. Accordingly, the aim of our systematic review with network meta-analysis was to determine the comparative effectiveness and safety of psychological interventions for chronic non-specific low back pain.
PainRelief.com Interview with: Eric L. Garland, PhDLCSW Distinguished Endowed Chair in Research Distinguished Professor and Associate Dean for Research University of Utah College of Social Work University of Utah, Salt Lake City www.drericgarland.com
Dr. Garland
PainRelief.com: What is the background for this study? What are the main findings?
Response: This was a 5-year NIH-funded clinical trial conducted in the primary care setting. Mindfulness-Oriented Recovery Enhancement reduced opioid misuse by 45%, more than doubling the effect of standard supportive psychotherapy, and far exceeding the effect size of any known therapy for opioid misuse among people with chronic pain. At the same time, MORE decreased chronic pain symptoms to a greater extent than the current gold-standard psychological treatment for chronic pain, CBT. MORE also decreased emotional distress and depression.
PainRelief.com Interview with: Lauren R. Gorfinkel MPH New York State Psychiatric Institute New York, NY Department of Medicine, University of British Columbia Vancouver, Canada
PainRelief.com: What is the background for this study?
Response: The opioid crisis has led to clear declines in opioid prescribing across North America, however, chronic pain remains an extremely common health problem with limited treatment options. This study was therefore interested in using nationally-representative data to find out whether alternative pain medications are growing more popular as opioid prescriptions decline.
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.
PainRelief.com Interview with: Carlen Reyes PhD Médico de familia Gestora de proyectos de investigación IDIAP Jordi Gol
PainRelief.com: What is the background for this study? What are the main findings?
Response: Tramadol and codeine are two “weak” opioids frequently prescribed for different non-cancer pain indications, however, few are the studies that compare the adverse outcomes between them using large routinely collected primary care data. We aimed to fulfil this gap by analysing the risk of adverse events with the tramadol and codeine dispensations in a large primary care health care data (SIDIAP database) from Spain.
We found that the dispensations of tramadol were associated with a greater risk of cardiovascular events, mortality and fractures compared to the dispensations of codeine.
Serena L. Orr, MD, MSc, FRCPC, FAHS Assistant Professor Depts of Pediatrics, Clinical Neurosciences and Community Health Sciences Cumming School of Medicine, University of Calgary Director, Pediatric Headache Program Alberta Children’s Hospital
Dr. Orr
PainRelief.com: What is the background for this study?
Response: Stress has long been felt to be one of the most common trigger factors for migraine. However, there is very little data on the relationship between stress and pain severity in individuals with migraine on a day-to-day basis, and this relationship is even more poorly understood among individuals with more frequent attacks, such as those with chronic migraine (who have at least 15 days/month of headache, 8 or more of which meet criteria for migraine attacks).
This was a study that looked at daily electronic headache diary data for 136 adults with chronic migraine, using data from the N1-Headache application. In this study, we aimed to understand the relationship between perceived stress and pain severity in individuals with chronic migraine. Individuals completed 90 days of daily diary entries where they reported on their headache characteristics, and their perceived stress levels, measured on a scale of 0-10.
PainRelief.com Interview with: Kanu M. Okike, MD Orthopedic Surgeon The Hawaii Permanente Medical Group
PainRelief.com: What is the background for this study? What are the main findings?
Response:Hip corticosteroid injections are a common treatment for osteoarthritis and other hip conditions. Recently, isolated case reports have raised the question of whether hip corticosteroid injections could be associated with rapid progression of the arthritis process – a condition known as rapidly destructive hip disease (RDHD).
PainRelief.com Interview with: Stuart L. Silverman MD FACP FACR Clinical Professor of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine Medical Director, OMC Clinical Research Center Beverly Hills, CA 90211
Dr. Silverman
PainRelief.com: What is the background for this study?
Response: As a practicing rheumatologist, I am aware that prior studies have shown variation in medical care, pain management and treatment with opioids by race and social economic status. Suboptimal treatment of pain in patients with osteoarthritis (OA) may also disproportionately burden racial minorities and Medicaid recipients.
Studies have shown that African Americans are nearly 1.5 times as likely to have symptomatic knee OA than White patients even when adjusting for other factors. Similarly, they also have a higher prevalence of symptomatic and radiographic hip OA. Analyses of Medicare data has shown evidence of persistent racial disparities for joint arthroplasty usage and surgical outcomes.
PainRelief.com Interview with: Dan P. Ly M.D., M.P.P., Ph.D. Division of General Internal Medicine and Health Services Research David Geffen School of Medicine University of California, Los Angeles
PainRelief.com: What is the background for this study? What are the main findings?
Response: We know that minority patients were less likely to receive opioids than white patients, but this could have been due to minority patients seeing lower opioid-prescribing physicians. As far as I could tell, nobody had been able to examine whether the same physician prescribed opioids differently to their minority patients.
I find that this is the case: the same physician was less likely to prescribe opioids to their minority patients with new low back pain, and instead was more likely to prescribe NSAIDs to their minority patients. And unfortunately, this differential prescribing may have had the consequence of leading to more chronic opioid use in white patients.
PainRelief.com Interview with: Louise Fleng Sandal PhD Adjunkt, Institut for Idræt og Biomekanik SDU University of Southern Denmark
Dr. Sandal
PainRelief.com: What is the background for this study?
Response:Low back pain is a globally prevalent condition with a high economic cost. Many people seek help with primary care from their general practitioner, physiotherapist or chiropractor. Evidence-based guidelines on first line treatment include learning to self-manage, staying active, exercising and learning about the condition. However, many find this difficult without advice and support, but primary care physicians often lack the time and resources to support self-management.
Digital solutions, such as smartphone technology, utilizing artificial intelligence can be used to tailor self-management support to the individual and be available at the individuals convenience.
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