Selenium Level Can Affect Liver Toxicity When Acetaminophen is Used for Pain Relief

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PainRelief.com Interview with:

Dr Charareh Pourzand PhD/DSc, FHEA, FRSB
Reader in Biopharmaceutics
Medicines Design Theme Leader
Head of UVA Photobiology, Iron & Oxidative stress group
Department of Pharmacy & Pharmacology
Centre for Therapeutic Innovation
University of Bath, Bath, United Kingdom



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

Response: It is recognized that acetaminophen (also known as paracetamol), a medication that is globally used for fever and pain, can cause acute liver damage when taken at higher level than the recommended dose.

This study demonstrated that acetaminophen can decrease the mouse liver’s antioxidant capacity by decreasing both the level of thioredoxin reductase (a selenoprotein and antioxidant enzyme) activity and glutathione (GSH, an antioxidant molecule) content in a dose- and time-dependent manner. These decreases also correlated with the extent of the liver damage exerted by acetaminophen. In addition, both mild-deprivations in selenium or excess selenium supplementation diets increased the extent of liver injury compared with mice with normal dietary selenium levels.  

In acetaminophen-treated mice, animals reared on selenium-deficient and excess selenium-supplemented diets also exhibited an increase in the oxidation state of the thioredoxin reductase-mediated system in subcellular compartments of the hepatocytes, notably in mitochondria which is the energy factory of the organism.

These observations revealed how the alteration of the function of the main antioxidant thioredoxin and GSH systems by acetaminophen is linked to hepatotoxicity.  Moreover it became apparent that the maintenance of the redox environment by thiols is a crucial determinant for the extent of acetaminophen-induced liver toxicity. Finally our study revealed the importance of dietary selenium level and the selenoproteins activity in protecting mice against the liver failure that can occur in acetaminophen overdose.

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Virus-Delivered Gene Therapy Provides Hope for Neuropathic Pain Relief

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PainRelief.com Interview with:
Sujeong Kim, PhD
Institute of BioInnovation Research, Kolon Life Science
Kolon One&Only Tower
Seoul Korea

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

Response: Neuropathic pain (NP) results from a lesion or disease affecting the somatosensory system, according to the International Association (IASP) for the Study of Pain. NP is difficult to treat and drastically influences an individual’s quality of life. Current treatment for NP aims to relieve pain and maintain patient function but does not address the etiological causes or alter the course of the condition. The causes of NP are many and varied in their scope, such as nerve injury, neuroinflammation, and abnormal pain signal transmission. NP has a multifactorial pathogenesis and their pathophysiology is the results of a very complex series of cross-linked pathway. There are limitations in treating pathogenesis by targeting only one path, so simultaneous targeting of multiple elements in NP is crucial for the treatment of the disease. Effective and disease-modifying options for NP treatment are urgently needed. We developed an AAV-based gene therapy, KLS-2031 (developed by KolonLifeScience Inc), for the expression of three therapeutic genes (encoding glutamate decarboxylase 65 (GAD65), glial cell-derived neurotrophic factor (GDNF), and interleukin 10 (IL-10)) to achieve the effective and long-lasting relief of NP.

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Can Placebos Be Effective Even If We Know It’s Not a ‘Real’ Drug?

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pain relief placebos

Darwin A. Guevarra, Ph.D.
Postdoctoral Fellow
Michigan State University

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

Response: Placebos are these inactive treatments that often work because people believe they are taking a real treatment. For the most part, they have real beneficial effects. However, there’s a utility-ethical issue when it comes to placebos. On one hand, they reliably work in managing daily nonclinical nuisance like emotional distress and even a host of clinical ailments like pain and depression. But, it seems like you have to lie to people that they’re taking a real treatment in order to get placebos to work. As it turns out though, there’s over a dozen studies showing that placebos can still work even when people are fully aware they are taking them. These studies educate participants about the placebo effects, how they work, and how they can probably still work even when people know they are taking one. This really opens up the possibility of ethically harnessing the beneficial effects of placebos. But there’s one glaring issue. These studies that found positive effects of non-deceptive placebos only show it with self-report and no studies show beneficial effects on biological measures. This casts some doubt on whether these self-reported beneficial effects are real.

Our study wanted to test if we can observe non-deceptive placebo effects on objective biological markers. In this case, we used a neural measure called the late positive potential that can track emotional distress. We find that non-deceptive placebos do reduce self-reported, but more importantly, neural measures of emotional distress.

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Is Spinal Manipulation Better Than Placebo for Low Back Pain Relief?

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PainRelief.com Interview with:
James S Thomas, PT, PhD
Professor
Departments of Physical Therapy and Physical Medicine and Rehabilitation
Director of Motor Control Laboratory
Virginia Commonwealth University
Departments of Physical Therapy and Physical Medicine and Rehabilitation
Director of Motor Control Laboratory
Virginia Commonwealth University
Richmond, VA 23298

Dr-James-Thomas
Dr. Thomas

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

Response: While there are numerous studies on spinal manipulation which is typically defined as  high velocity short amplitude thrust procedure to treat a hypomobile vertebral segment, there are very few studies that examine spinal mobilization (typically described as non-thrust or as a muscle energy technique). There are even fewer studies on the comparative effectiveness of these interventions. 

Accordingly, the RELIEF study was designed to provide a rigorous examination of the comparative effectiveness of the two most common manual therapy techniques for treating low back pain (i.e., manipulation versus mobilization) compared to an effective placebo (i.e., Sham Cold Laser).

PainRelief.com: What are the main findings?

Response: Relative to the placebo group, there was no difference in the change in pain or disability for either spinal manipulation or mobilization. 

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Deprescribing Opioids Used For Chronic Non-Cancer Pain Relief

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PainRelief.com Interview with:
Dr Stephanie Mathieson PhD
NHMRC Health Professional Research Early Career Fellow
The University of SydneyFaculty of Medicine and Health, Sydney School of Public Health
Australia

Dr Stephanie Mathieson is a Research Fellow at the Institute for Musculoskeletal Health, The University of Sydney. Her National Health and Medical Research Council (NHMRC) Health Professional Research Early Career Fellow is focused around reducing the opioid epidemic in Australia.

Dr. MATHIESON

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

Response: This study aimed to review the current evidence of the efficacy of interventions designed to reduce/cease the prescription of, or the use of, opioid analgesics in patients with chronic non-cancer pain.

As clinical practice guidelines now discourage the initial prescription of opioid analgesics for chronic non-cancer pain, clinicians need to know which opioid dose reduction methods are most effective and safe for deprescribing opioid analgesics in their patients.

PainRelief.com:?  What are the main findings?

Response: Our systematic review extended the previous body of literature by incorporating five new randomised trials; however, clinical and statistical heterogeneity prevented meta-analysis. There were ten patient-focused interventions (i.e. aimed at reducing a patient’s opioid dose), and two clinician focused interventions (i.e. aimed at changing the clinician’s behaviour). Overall, our review was unable to recommend any one opioid analgesic deprescribing strategy in patients with chronic pain due to the small number of trials and heterogeneity.

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Are Off-Label Gabapentinoids Useful for Post-Operative Pain Relief?

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PainRelief.com Interview with:
Michael Verret MD FRCPC
Alexis F. Turgeon MD MSc FRCPC
Laval University, Québec

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

Response: Gabapentinoids is a class of drugs including gabapentin and pregabalin that is frequently used for the management of postoperative pain as a part of multimodal analgesia regimen. This off-label use of gabapentinoids is increasing in many countries despite an unclear level of evidence and off-label use.

In our meta-analysis of 281 randomized controlled trials, the perioperative use of gabapentinoids was not associated with clinically significant difference in postoperative acute, subacute or chronic pain intensity compared to control. These findings were consistent regardless of the type of drug (gabapentin or pregabalin) and the dosage regimen. Gabapentinoids were also associated with an increased risk of adverse events such as dizziness and visual disturbance.

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PET Probe Pinpoints Sites of Pain Generation to Improve Pain Management

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PainRelief.com Interview with:
Sandip Biswal MD
Associate Professor of Radiology
Co-Section Chief, Musculoskeletal Imaging
Director, Musculoskeletal Imaging Fellowship
Member, Molecular Imaging Program at Stanford (MIPS) and Bio-X
Department of Radiology
Stanford University School of Medicine

PainRelief.com:  What is the background for this study?
Response: Our ability to manage patients with chronic pain remains woefully inadequate. Chronic pain patients are faced with limited resources and inadequate care, and as a result, they make up the #1 disease group in the world—numbering more than heart disease, diabetes and cancer combined. Those suffering from low back pain, headache, fibromyalgia, arthritis and many other pain syndromes make up this ever-growing population. A big part of our inability to care for chronic pain patients is due to the fact that our current imaging methods for correctly identifying pain generators remain substantially inaccurate. Our ability to accurately identify the cause of a person’s pain, discomfort, inflammation or other related musculoskeletal symptom(s) using current clinical imaging approaches, such as magnetic resonance imaging (MRI), computed tomography (CT), digital radiography (x-ray) and ultrasound, is quite limited, lacks sensitivity/specificity and can even misguide treatment. As a musculoskeletal radiologist, I witness these shortcomings on a daily basis. I, for example, see firsthand how the lack of reliable diagnostic tools leads to significant misdiagnosis, mismanagement, incorrect use of opioids, unhelpful surgeries and, ultimately, therapeutic failures. We need a much better way to diagnose pain generators. 

Accordingly, our group has been developing new clinical imaging methods that pinpoint the site of pain generation using imaging probes—more specifically, positron-emission tomography (PET) tracers that specifically target “pain receptors” or “pain molecules.” These pain receptors or pain molecules are present in abundance at the site of pain generation. After injecting one of these imaging probes into a patient through the vein, we give the probe a few minutes to circulate around the body and stick to areas that have a high density of pain receptors. We can then take a picture of the patient with a special camera that will show “hot spots” on the image that signify the location of high number of pain receptors, thereby highlighting “painful” pro-inflammatory and/or pro-nociceptive tissues. With this approach, doctors and patients have information with which they can make more objective decisions about the diagnosis and treatment of one’s pain.

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Joint Replacement: Have Opioid Prescription Patterns for Pain Relief Changed?

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PainRelief.com Interview with:
Rahul Shah
Medical Student
The University of Texas Medical Branch

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

Response: The United States has a unique overreliance on opioids for managing both acute and chronic pain, compared to many other developed nations. Opioid misuse and addiction frequently start with large doses of opioids prescribed after surgical interventions. This overprescribing contributes to the high rates of opioid use disorder and overdose deaths in the United States. There have been myriad interventions to curb opioid overprescribing, ranging from the DEA’s hydrocodone rescheduling law to opioid prescribing guidelines issued by the CDC, states and orthopedics specialty organizations. 

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Study Finds Common Sports Procedures Can Be Performed with No Opioids for Pain Relief

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PainRelief.com Interview with:

Kelechi R. Okoroha, M.D. 
Division of Sports Medicine
Department of Orthopedic Surgery
Henry Ford Health System

Dr. Okoroha

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

Response: The United States is in the midst of an opioid epidemic. Postoperative prescriptions following surgery is thought to have a direct role in the availability and exposure of opioids to the general population. This study was created in order to assess the viability of having common sports surgeries without the use of opioids.

PainRelief.com: What are the main findings?

Response: Our studies main findings were that common sports procedures can be performed with little or no opioids. 45% of patients did not require breakthrough opioid medication and all patients were satisfied with their pain management. Factors that were associated with requiring opioids included history of anxiety/depression.

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Non-Opioid Orphengesic Forte Approved for Mild-to-Moderate Pain Relief due to Acute Musculoskeletal Conditions

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PainRelief.com Interview with:
Brian Cheng, PharmD
Senior Manager, Medical Affairs
Galt Pharmaceuticals

PainRelief.com:  What is the background for this announcement

Response: Galt Pharmaceuticals announced a new drug approval to offer a non-opioid, non-controlled, non-addictive alternative for healthcare providers to manage patients suffering from pain. On July 8, 2020, the U.S. Food and Drug Administration approved the company’s Supplemental Abbreviated New Drug Application for Orphengesic Forte (Orphenadrine Citrate, Aspirin, Caffeine tablets 50mg/770mg/60mg), over two months ahead of the scheduled goal date.

Orphengesic Forte is indicated for the relief of mild to moderate pain of acute musculoskeletal disorders, paired with rest, physical therapy and other measures. (More Important Safety Information is below.)

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