PainRelief.com Interview with: John Traynor, PhD Edward F Domino Research Professor Professor and Associate Chair for Research Department of Pharmacology, Medical School Professor of Medicinal Chemistry, College of Pharmacy University of Michigan, Ann Arbor MI
Dr. Traynor
PainRelief.com: What is the background for this study? What are the main findings?
Response: Response: Morphine and related drugs acting at the mu-opioid receptor are the most effective treatment for moderate to severe pain, yet their use is limited by serious on-target side effects including respiratory depression, and physical and psychological dependence that has led to the opioid crisis. Current opioid drugs are required because our own endogenous pain relieving chemicals, the enkephalins and endorphins opioid peptides, cannot efficiently relieve pain.
We have discovered a class of drugs (positive allosteric modulators, PAMs) that bind to the mu-opioid receptor to enhance the activity of endogenous opioids. These “enkephalin amplifiers” afford pain relief in mouse models without the need for morphine-like compounds and do so with a much reduced side-effect profile.
PainRelief.com Interview with: Jim Whedon DC, MS Director of Health Services Research SCU Health System Southern California University of Health Sciences Whittier, CA
PainRelief.com: What is the background for this study?
Response: Current evidence-based guidelines for clinical management of chronic low back pain (cLBP) include both pharmacological and non-pharmacological approaches.
Both Opioid Analgesic Therapy (OAT and Spinal Manipulative Therapy (SMT) are effective treatments for cLBP and are provided under Medicare for older adults with cLBP, but the long-term safety of OAT is uncertain, and the dangers of opioid misuse are well known. Older adults are at particularly high risk of adverse drug events (ADEs),but they nevertheless receive more opioid analgesics than any other age group. SMT is established as an effective non-pharmacologic treatment for cLBP, but little is known about the safety of long-term treatment with SMT.The objective of our study was to compare SMT and OAT to determine the impact of SMT on the risk of ADEs among older adults receiving long-term care for cLBP.
PainRelief.com Interview with: Ana M Valdes MA PhD Professor in Molecular and Genetic Epidemiology NIHR Nottingham Biomedical Research Centre – Research Area Lead Associate Editor European Journal of Clinical Nutrition School of Medicine University of Nottingham
Dr. Valdes
PainRelief.com: What is the background for this study?
Response: Knee osteoarthritis and knee pain affect a large proportion of middle age and aging individuals and this are an increasing problem. Physical exercises aimed at strengthening and stabilising the muscles in the legs and hips are known to be highly effective in reducing pain and improving the ability to walk and get on with life. But a key challenge is how to deliver such gradual exercises in a way that does not require people to travel to see a physiotherapist or a doctor, particularly given the issues raised by lockdown both in terms of the Covid-secure challenges face to face visits and also given the strain that the pandemic has put on health services.
Our study was the first randomised controlled trial in the UK where we were had people with painful knee osteoarthritis either do only what their doctors normally recommend or, in addition, follow a programme of exercised developed in Sweden delivered via smartphone app. The research participants were assessed for knee inflammation, knee pain, pain sensitivity around the knee, muscle strength, and ability to walk and get up from a chair both before and after the 6 week smartphone delivered intervention (or a 6 week period simply following any advice they had from their family doctor).
PainRelief.com Interview with: Markus Ploner MD Professor of Human Pain Research Department of Neurology Technische Universität München Munich, Germany
Prof. Ploner
PainRelief.com: What is the background for this study?
Response: Recent studies in humans and animals have revealed that pain is associated with rhythmic brain activity termed neural oscillations. In particular, changes of neural oscillations at alpha (8 – 13 Hz) and gamma (30 – 100 Hz) frequencies in somatosensory and prefrontal brain areas have been related to pain. Thus, modulating neural oscillations to eventually modulate pain is a promising novel approach for pain treatment.
Transcranial alternating current stimulation (tACS) is an emerging neuromodulation technique which aims at non-invasively modulating neural oscillations in the human brain. During tACS, a weak alternating current is applied to the scalp with the goal of entraining neural oscillations at the stimulation frequency, thereby increasing their amplitude. The appeal of tACS is that it is non-invasive, safe, cost-efficient, and potentially mobile which allows for broad clinical applications. Thus, tACS is increasingly explored as a new treatment approach for neuropsychiatric disorders.
In our study, we therefore explored the potential of tACS to modulate pain. We systematically applied tACS at alpha and gamma frequencies or sham tACS over somatosensory and prefrontal cortices during tonic experimental pain in healthy human participants.
PainRelief.com: What are the main findings?
Response: Our main findings are that, using the current setup, tACS did not modulate the perception of pain. Bayesian statistics further supported a lack of tACS effects in most conditions including prefrontal and gamma tACS. The only exception was tACS at alpha frequencies over somatosensory cortex where evidence for tACS effects on pain perception was inconclusive.
PainRelief.com: What should readers take away from your report?
Response: Readers might take away three key points.
First, neurophysiological studies indicate that modulating neuronal oscillations to eventually modulate pain is a promising novel approach for the treatment of pain.
Second, tACS is one non-invasive and simple approach to modulate neuronal oscillations.
Third, our mostly negative findings show that we are not there yet.
PainRelief.com: What recommendations do you have for future research as a result of this work?
Response: A very general recommendation is that rigorous, well-controlled and transparent studies are needed to further explore the potential of tACS (and other neuromodulatory techniques) for treating pain. Furthermore, we should ideally make all our data available to the public so that the whole research community can take advantage of them. Finally, to advance the field, we should not only publish positive but also negative findings, as done here.
A more specific recommendation is that modulating neuronal oscillations at alpha frequencies over somatosensory brain areas is the most promising approach for further tACS studies.
Citation:
May ES, Hohn VD, Nickel MM, Tiemann L, Gil Ávila C, Heitmann H, Sauseng P, Ploner M. Modulating Brain Rhythms of Pain using Transcranial Alternating Current Stimulation (tACS) – A Sham-controlled Study in Healthy Human Participants. J Pain. 2021 Apr 9:S1526-5900(21)00191-7. doi: 10.1016/j.jpain.2021.03.150. Epub ahead of print. PMID: 33845173.
The information on PainRelief.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.
PainRelief.com Interview with: David E. Fisher MD, PhD Edward Wigglesworth Professor & Chairman Dept of Dermatology Director, Melanoma Program MGH Cancer Center Director, Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School
Dr. Fisher
PainRelief.com: What is the background for this study?
Response: This study followed up on prior published work from other investigators which demonstrated altered pain thresholds in humans and mice who had the redhair light-skin phenotypes. The key focus of our current study was to firstly validate the overall findings, and then to the mechanistic basis for the differences. Of note, our laboratory does not primarily focus on the science of pain or nociceptive, but rather on skin and melanoma. For this reason we had accumulated a number of valuable genetic models of pigmentation (such as redhaired mice harboring alterations in the identical gene implicated in human red hair). These mouse models served as the key resources for carrying out the current study.
PainRelief.com Interview with: Dulanji K. Kuruppu, MD Medical Advisor, Migraine & Headache Disorders US Medical Affairs Eli Lilly and Company LTC-South, Indianapolis IN 46221 U.S.A.
PainRelief.com: What is the background for this study?
Response: Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine and for the treatment of episodic cluster headache in adults. The CONQUER study assessed the efficacy and safety of galcanezumab in 462 adults with episodic or chronic migraine who previously did not benefit from 2 to 4 standard-of-care migraine preventive medication categories. This study consisted of a 3-month double-blind, placebo-controlled period (months 1-3) followed by an open-label period (months 4-6). The primary endpoint, which was the mean change from baseline in the number of monthly migraine headache days for galcanezumab vs placebo over months 1-3, was met. In this post-hoc analysis, we assessed onset of effect of galcanezumab in the CONQUER population.
PainRelief.com Interview with: Jason R. Levy, MD, FSIR Vascular and Interventional Radiologist Northside Hospital in Atlanta, Georgia
Dr. Levy
PainRelief.com: What is the background for this study?
Response: For patients whose cancer has spread to their bones, their pain is often treated using radiation, which can take weeks to provide relief. In our study we examined the effectiveness of Radiofrequency Ablation (RFA) for the palliative treatment of patients with painful osseous metastases.
Radiofrequency Ablation is a minimally invasive treatment that uses radiofrequency waves to create heat that kills tumor cells and destroys nerve fibers to reduce transmission of pain signals to the brain. The procedure was followed up with cement injections to help stabilize the bone and prevent fractures that often occur following other treatments.
PainRelief.com Interview with: Fred Cohen, MD Department of Medicine, Montefiore Medical Center and the Albert Einstein College of Medicine Bronx, New York
Dr. Fred Cohen
PainRelief.com: What is the background for this study?
Response: OnabotulinumtoxinA (onabot) and calcitonin gene-related peptide monoclonal antibodies (CGRP-targeted mAbs) are two medications used to treat chronic migraine. While both have been shown to significantly reduce monthly headache days, they are some patients that require further treatment after receiving one of these therapies. Prior to this study, there was limited data on the efficacy and safety of concomitant treatment with onabot and a CGRP-targeted mAb.
PainRelief.com Interview with: Shannon Lovett, MD, FACEP Associate Professor Associate Medical Director, ED Clinical Operations Department of Emergency Medicine Stritch School of Medicine
Dr. Lovett
PainRelief.com: What is the background for this study? What types of pain were treated?
Response: The opioid crisis has led emergency medicine providers to utilize other medications to treat pain, including ketamine. Prior to our study, there was a range of recommended ketamine doses in the treatment of pain, and the most frequently studied dose demonstrating analgesic efficacy was 0.3 mg/kg. We challenged that dose by comparing a lower dose, 0.15 mg/kg, to 0.3 mg/kg of IV ketamine for acute moderate to severe pain in the emergency department. We treated acute (onset < 7 days) abdominal, back, flank, musculoskeletal, and headache pain.
Mary K. Mulcahey, MD, FAAOS, FAOA Director, Women’s Sports Medicine Program Associate Professor Assistant Program Director Department of Orthopaedic Surgery Tulane University School of Medicine New Orleans, LA
PainRelief.com: What is the background for this study? What are the main findings?
Response: Osteoarthritis Research Society (OARSI) guidelines include topical non-steroidal anti-inflammatory drugs (NSAIDs) as a level 1A recommendation for non-operative management of knee osteoarthritis, but previous reviews have demonstrated that clinical adoption of this treatment option lags. We conducted a systematic review and meta-analysis of 18 studies evaluating diclofenac, ketoprofen, and ibuprofen in topical preparations. We found that they are safe and effective for reducing pain and improving physical function in patients with knee osteoarthritis. Diclofenac had the strongest quality and number of studies and showed a moderate effect size for symptomatic improvement. With regards to safety, adverse events were low in the topical treatment groups, and topical preparations containing dimethyl sulfoxide (DMSO) showed a higher odds ratio for adverse events than preparations without DMSO.
The information on PainRelief.com is provided for educational purposes only, and is in no way intended to diagnose, endorese, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. None of the content on PainRelief.com is warranted by the editors or owners of PainRelief.com or Eminent Domains Inc.
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