Total Knee Replacement: Outcomes by Age vs Co-Morbidities

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.

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Migraine: Genetic Factors May Differ Between Men and Women

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.

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Minimally Invasive Spinal Surgery for Leg or Back Pain Linked to Improved Pain Relief and Function

PainRelief.com Interview with:
Dr. Mohamad Bydon MD
Professor of Neurosurgery
Mayo Clinic
Rochester, Minnesota

:Dr. Bydon MD

PainRelief.com:  What is the background for this study?

Response: Patients presenting with back or leg pain due to degenerative lumbar spine disease often undergo spinal fusion to mitigate the symptoms and halt the progression of the disease.

PainRelief.com: What are the main findings?

Minimally invasive surgery (MIS) in the lumbar spine encompasses a variety of techniques, such as percutaneous screw placement and operation via tubular retractors, and aims to limit the distortion of patients’ anatomy as much as possible. Eventually, compared to open fusion, MIS fusion is associated with decreased muscle destruction, incision size, and time-to-mobilization.

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Large Study of Painful Cluster Headaches Has Revealing Findings

PainRelief.com Interview with:
Mark J. Burish, MD, PhD.
Assistant Professor
Vivian L. Smith Department of Neurosurgery
Director, Will Erwin Headache Research Center
McGovern Medical School at UTHealth Houston

Dr. Mark Burish – Neurosurgery
Photo by Dwight C. Andrews/The University of Texas Medical School at Houston Office of Communications

PainRelief.com:  What is the background for this study?  Would you describe cluster headaches?

Response: Cluster headache is a disease associated with excruciating attacks of one-sided pain around the eye – patients regularly say it is more painful than childbirth, kidney stones, or gunshot wounds.  The attacks last between 15 minutes and 3 hours and can occur up to 8 times per day.  During an attack, patients will often have changes around the eye (such as a watery or bloodshot or droopy eye) changes in the nose (like congestion and a runny nose), and a restless feeling like they can’t sit still.  It is called “cluster” headache because, for most patient, the headaches occur every day for several weeks then go away for the rest of the year, only to come back the following year.  This is called “episodic” cluster headache, though there is another version called “chronic” cluster headache in which the headaches occur at least 9 months a year.

Cluster headache is found in about 1 in 1000 patients.  Because it is uncommon, there have not been a lot of large international studies investigating basic questions like the age that these headaches start and the differences from patient to patient.  There is a great need to understand more about this disorder at every level.  So two researchers from the University of West Georgia (Larry Schor and Stuart Pearson) performed a large epidemiology study on cluster headache because very few have been done.  They created an online questionnaire and advertised it internationally.  They ended up obtaining the largest study in terms of participants and the most international study ever performed (at least to our knowledge).  They then asked for help analyzing it from several physicians (including myself) and statisticians.  I felt very fortunate that they reached out to me and I really enjoyed working on this project because I think it gives us a lot of insights into cluster headache.

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Cooled Radiofrequency Ablation for Pain Relief After Total Knee Replacement

PainRelief.com Interview with:

Felix Gonzalez, M.D.
Assistant professor, Division of Musculoskeletal Imaging
Department of Radiology and Imaging Scienc
Emory University School of Medicine
Atlanta, Georgia

Dr. Gonzalez

PainRelief.com:  What is the background for this study?  What are the main findings?

Response: Total knee arthroplasty is a common procedure performed worldwide for the treatment of symptomatic knee arthritis. Unfortunately, approximately 20% of those patients develop chronic pain after the surgical intervention in the setting of no complications such as infection or hardware loosening. The reason for this is not known at this point although theories exist.

The new study focused on 21 patients who were experiencing persistent chronic pain after total knee replacement, without underlying hardware complications. The patients had all failed conservative care. They filled out clinically validated questionnaires to assess pain severity, stiffness, functional activities of daily living and use of pain medication before and after the procedure. Follow-up outcome scores were collected up to one year after the C-RFA procedure.

In the end, the study found, patients with knee arthritis reported an 70% drop in their pain ratings approximately, on average.

Study Compares PRP to Placebo For Pain Relief in Knee Arthritis

PainRelief.com Interview with:

Professor Kim Bennell FAHM
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.

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Case Report Describes Pain Relief from Chronic Migraines with LIFE Diet

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:

https://journals.sagepub.com/doi/full/10.1177/1559827619894954 

and https://journals.sagepub.com/doi/full/10.1177/1559827620962458.

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.

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Less-is-More Approach to Pain Relief After Surgery

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.

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Study Finds Physical Exercise Increases Body’s Own Cannabis-Type Substances

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.  

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Study Identifies New Compound That Alleviates Chronic Pain in Preclinical Models

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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