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 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.

Continue reading

UCI Scientists Discover Pathway Blocking Transition from Acute to Chronic Pain

PainRelief.com Interview with:

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
Dr. Piomelli

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.  

Continue reading

Study Addresses How Weather Affects Pain Tolerance

PainRelief.com Interview with:
Erlend Hoftun Farbu, PhD student
Department of Community Medicine
The Arctic University of Norway
Tromsø, Norway

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

Response: Many report that weather affect their pain condition. Some studies confirm this, others do no. However, these studies have asked “How much pain do you have today?”

We used two tests to assess how much pain a person can tolerate. We then looked at how pain tolerance vary over time and if they are associated with weather.

The results show quite clearly that people can tolerate more pain caused by intense cold temperature in the colder months of the year. There was no such seasonal variation in pain caused by pressure to the leg. On the other hand, we found that both pressure pain tolerance and weather at one day was associated with the next days, but not the next month. When we further linked the weather and pain tolerance, we found that, for example, in some periods a rise in temperature happened at the same time as a rise in pain tolerance. While in other periods, there were no such association. We mean that this is because we adapt to the weather. For example, how we experience 5 °C (41°F) is different in autumn and spring..

Finally, temperature and barometric pressure could predict future values of pressure pain tolerance

Continue reading

Switching to Buprenorphine Might Provide Pain Relief for Poorly Controlled Pain

PainRelief.com Interview with:
Victoria D. Powell, MD, FACP
Clinical Lecturer – Geriatric and Palliative Medicine
University of Michigan
Staff Physician, Palliative Care
LTC Charles S. Kettles VA Medical Center
Ann Arbor, MI

Dr. Powell

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

Response: People with chronic pain who use long-term opioids face a number of health risks, and often do not have optimally controlled pain.

Buprenorphine acts on the opioid receptor with a different effect than drugs like morphine or oxycodone, and as a result is less associated with the risks of long-term opioid use, such as accidental overdose. While buprenorphine has been successfully used in patients with opioid use disorder for several years, certain experts have proposed using buprenorphine for pain management in people with chronic pain. We found low quality evidence supporting pain control that may be superior to traditional opioids, but much more research is needed to confirm.

Continue reading

Medical Cannabis May Be Helpful For Pain Relief in a Minority of People with Chronic Pain, But Will Not Be Effective For Most

PainRelief.com Interview with:
JASON BUSSE DC, PhD
Associate Professor
Associate Director
Michael G. DeGroote Centre for Medicinal Cannabis Research
McMaster University Medical Centre
Ontario, Canada

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

Response: Our focused clinical practice guideline was informed by 4 systematic reviews exploring benefits and harms of medical cannabis for chronic pain, the potential for cannabis to help people who live with pain to reduce their use of opioids, and patients values & preferences regarding medical cannabis for chronic pain. We found that non-inhaled medical cannabis provided small to very small improvements in pain relief, physical functioning and sleep quality compared to placebo, but did not improve mental functioning, role functioning or social functioning. Use of medical cannabis, versus placebo, also caused small increases in the risk of several transient, moderate, side effects, such as impaired attention, nausea, and drowsiness, and a larger increase in the risk of dizziness.

There was insufficient evidence to inform the risk of serious adverse events, such as motor vehicle accidents, cannabis use disorder (addiction), or suicide. We also found that patients’ attitudes towards medical cannabis show considerable variation, meaning that when presented with the same evidence different patients are likely to make different decisions about embarking on a trial of medical cannabis. Due to the close balance between modest benefits and harms, and high variability among patients’ attitudes, we made a weak recommendation to consider a trial of medical cannabis for people living with chronic pain who had not achieved sufficient relief with standard care.

A weak recommendation means that clinicians should provide chronic pain patients with the evidence for benefits and harms and help them to make a decision consistent with their patient’s values and preferences.

Continue reading

Synovial Stem Cells Injected into Knee Repaired Meniscus without Tumor Formation

PainRelief.com Interview with:
Mitsuru Mizuno, DVM, Ph.D.
Assistant professor at CSCRM,
Principal investigator for this study
and Ichiro Sekiya, M.D., Ph.D..

PainRelief.com:  What is the background for this study?  What are the main findings? How are the stem cells obtained?

Response: We have developed a cell therapy for treating difficult-to-heal meniscus injury using mesenchymal stem cells (MSCs) derived from the synovium of the knee. However, trisomy 7 is often found in synovial cells obtained from patients with osteoarthritis, a disease that occurs with aging.

Continue reading

Pain in U.S. Adult Hispanics Varies by Their Ancestral Country of Origin

PainRelief.com Interview with:
Richard L. Nahin, Ph.D., M.P.H
Lead Epidemiologist
National Center for Complementary and Integrative Health (NCCIH)
National Institutes of Health
Bethesda, Maryland

Dr. Nahin

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

Response: Individuals of Hispanic ancestry living in the U.S. include numerous subpopulations that vary in the prevalence of chronic disabling conditions, as well as exhibit differences in socioeconomic status, health behaviors, global health status, health care utilization, and genetic profiles. 

Despite this evidence, there are few nationally representative studies examining the epidemiology of pain in these Hispanic subpopulations, and none that compared global measures of pain chronicity, severity, nor examined the influence of race on potential associations with pain in Hispanics.

Continue reading

Chronic Pain Increasing in Every Age and Demographic Group

PainRelief.com Interview with:
Hanna Grol-Prokopczyk PhD
Associate Professor
Department of Sociology
University at Buffalo, SUNY

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

Response: Although chronic pain is recognized as an extremely common and costly health problem, little research has explored temporal trends in pain prevalence.  Indeed, as recently as 5-6 years ago, there was no published research using general population data examining whether pain prevalence in the U.S. was going up, going down, or staying constant.  (This can be contrasted to conditions such as diabetes and cancer, for which information about long-term trends is readily available.  Of note, chronic pain affects more Americans than diabetes, cancer, and heart disease combined.)  In recent years, a few studies have documented rising pain prevalence in the U.S., but most have used data on middle-aged or older adults.

Continue reading

Tapentadol Provided Pain Relief and Improved Sleep in Patients with Chronic Musculoskeletal Pain

PainRelief.com Interview with:
Dr Renato Vellucci
Contract Professor University of Florence
Pain and Palliative care Clinic
University Hospital of Careggi
Florence, Italy

Dr. Vellucci

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

Response: Chronic low back pain (CLBP) is the most prevalent chronic pain (CP) condition and the leading global cause of years lived with disability. According to the axiom pain as a biopsychosocial issue, mood and sleep disturbances represent key issues. However, the impact of different analgesic therapies on quality of life (QoL) and functional recovery has been poorly assessed to date. Focusing on combination of chronic pain and sleep, they both perform a mutual reinforcement.

Pain disorganizes the sleep architecture, and disturbed and unrefreshed sleep increases spontaneous pain and lowers pain thresholds. Sleep disorders may augment stress levels, thus making it difficult for patients to perform simple tasks impairing their cognitive ability. Poor sleep may predict the growth and intensification of pain over time, with increased insomnia symptoms being both a predictor and an indicator of worse pain outcomes and physical functioning status over time. Epidemiology of chronic pain unequivocally demonstrates the role of sleep quality in the development of chronic pain.

Notwithstanding this strong two-way relationship between chronic pain and sleep, little knowledge is available about the neurochemical determinants of this interplay and therapeutical strategies to break this vicious circle. Fifty percent of people with chronic low back pain have sleeping disturbances, with an 18-fold increase in insomnia versus healthy people. A recent study investigated the relationship between sleep disturbances and back pain and found that it is two sided with sleep disturbance being associated with risk of back pain whilst back pain can also lead to sleep disturbances. Thus, it can be hypothesized that, by reducing pain and physical dysfunction, sleep quality could be improved, thus enriching the QoL of people with CLBP.

Similarly, improvements in sleep after cognitive behavioral therapy in patients with chronic pain due to osteoarthritis were associated with reduced pain. Earlier evidence suggested that tapentadol prolonged-release treatment ameliorate in parallel QoL and sleep quality in a greater proportion of patients compared to that of patients following oxycodone/naloxone prolonged- release treatment (50% versus 37.7%). Other tapentadol studies conducted in a real-life context documented, along with effective pain control, similar improvements in mental and physical health and suggested beneficial effects in terms of less night awakenings and greater percentages of patients reporting restful sleep.

Continue reading