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.
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.
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.
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.
PainRelief.com Interview with: Deepak Kumar, PT, PhD Assistant Professor, Physical Therapy Assistant Professor, BU School of Medicine Director, Movement & Applied Imaging Lab
Dr. Kumar
PainRelief.com: What is the background for this study? What are the main findings?
Response: We investigated the association of physical therapy interventions with long-term opioid use in people who undergo total knee replacement surgery. For people with advanced osteoarthritis, total knee replacement is the only option. The number of total knee replacement surgeries has been increasing and is expected to rise exponentially over the next few years with an aging population and rising rates of obesity. However, up to a third of patients continue to experience knee pain after this surgery. Also, a significant proportion of people become long-term opioid users after total knee replacement. Reliance on opioids may reflect a failure of pain management in these patients. Given that physical therapy interventions are known to be effective at managing pain due to knee osteoarthritis, we wanted to study whether physical therapy before or after surgery may reduce the likelihood of long-term opioid use.
We used real-world data from insurance claims for this study. In our cohort of about 67,000 patients who underwent knee replacement between 2001-2016, we observed that, receiving physical therapy within 90 days before surgery or outpatient physical therapy within 90 days after surgery were both related to lower likelihood of long-term opioid use later. We also observed that initiating outpatient physical therapy within 30 days and 6 or more sessions of physical therapy were associated with reduced likelihood of long-term opioid use compared to later initiation or fewer PT sessions, respectively. However, we did not see an association between type of physical therapy. i.e., active (e.g., exercsise) vs. passive (e.g., TENS) and long-term opioid use.
Importantly, most of our findings were consistent for people who had or had not used opioids previously. We also were able to account of a larger number of potential factors that could confound these associations because of the large sample size. However, there are limitations to our work. Since we only had access to insurance claims data but not to health records, we are unable to make any inferences about association of physical therapy with pain or quality of life, etc.
Daniele Piomelli PhD Distinguished Professor, Anatomy & Neurobiology Louise Turner Arnold Chair in Neurosciences Joint Appointment, Biological Chemistry and Pharmacology School of Medicine Director, Center for the Study of Cannabis University of California, Irvine
PainRelief.com: What is the background for this study?
Response: The pain caused by physical trauma or by surgery can disappear in a relatively short time — or linger for months or even years. In some cases, for example after open heart surgery, the percent of people who develop persistent pain can be as high as 40%. Breast and knee surgery, among others, have similar outcomes. We still don’t understand how acute pain after an injury becomes chronic.
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