Identification of the Muscle-Relaxant Carisoprodol (Soma) and Non-Controlled Prescription Substances in Drug-Arrests

PainRelief.com Interview with:
Maaz Siddiqui, BS
Department of Medical Education
Geisinger Commonwealth School of Medicine
Scranton, Pennsylvania

Maaz Siddiqui

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

Response: Over the last twenty years, the rise of deaths due to drug overdoses have been mainly and rightfully attributed to opioids. However, many investigations identify non-opioid drugs and drug classes that additionally contribute to deaths due to polysubstance overdoses. Through the Maine Diversion Alert Program (DAP) data, we examined drugs that often escape the attention of healthcare providers and directly or indirectly contribute to substance misuse, arrests, addiction, and deaths due to overdose.

The goal of this study was to utilize a novel dataset to uncover and identify the noncontrolled drugs that have shown potential to be misused.

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About 1/3 North Americans Self Medicate with Cannabis, Mostly for Pain

PainRelief.com Interview with:
Janni Leung, PhD
Senior Research Fellow
National Centre for Youth Substance Use Research (NCYSUR)
The University of Queensland

Dr. Leung

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

Response: There is increasing interest in cannabis use for medical reasons, and we want to find out how many people are using it and for what.

PainRelief.com:  What are the main findings?

Response: Almost 1 in 3 of North Americans self-reported that they have used cannabis for medical reasons, with higher use reported by young adults, although chronic conditions are less prevalent in this group.

Most common reasons were to help with pain, sleep, depression and anxiety, but some reported using it to manage their drug or alcohol use and psychosis.

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More Kids Poisoned by Cannabis Since Legalization

PainRelief.com Interview with:
Daniel Myran, MD, MPH, CCFP, FRCPC
Family and Public Health and Preventive Medicine Physician 
CIHR Fellow, Ottawa Hospital Research Institute 
Department of Family Medicine Innovation Fellow
University of Ottawa 

Dr. Myran

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

Response: Canada legalized recreational, or non-medical, cannabis in October 2018. Canada took phased approach to legalization initially only allowing flower-based cannabis products and oils and after one year permitting the sale of commercial cannabis edibles (e.g. THC containing candies, baked goods, and drinks). In this study we took advantage of this phased roll out of legal cannabis to understand the impact of legalization on cannabis exposures or poisonings in children aged 0-9 years and the contribution of different types of cannabis products to these events. 

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Risk of AMA Hospital Discharge High Among Patient with Opioid-Related Conditions

PainRelief.com Interview with:
Peggy Compton, RN, PhD, FAAN
Professor and van Ameringen Endowed Chair
Program Director, Hillman Scholars in Nursing Innovation
Department of Family and Community Health
University of Pennsylvania School of Nursing
Philadelphia, PA 19104

Dr. Compton

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

Response: Patients with substance use disorders are highly likely to leave the hospital against medical advice (AMA) or self-discharge, putting them at risk for poorer health outcomes including progressing illness, readmissions, and even death. Inadequate pain management is identified as a potential motivator of self-discharge in this patient population.  The objective of these secondary analyses was to describe the association between acute and chronic pain and AMA discharges among persons with opioid-related conditions.

PainRelief.com:  What are the main findings?

Response: The main findings were that 16% of the 7,972 admissions involving opioid-related conditions culminated in an AMA discharge, which was more than five times higher than in the general population. Self-directed discharge rates were positively associated with polysubstance use, nicotine dependence, depression, and homelessness. Among the 955 patients with at least one self-directed discharge, 15.4% had up to 16 additional self-directed discharges during the 12-month observation period. Those admitted with an acutely painful diagnosis were almost twice as likely to have an AMA discharge, and for patients with multiple admissions, rates of acutely painful diagnoses increased with each admission coinciding with a cascading pattern of worsening infectious morbidity over time. Chronic pain diagnoses were inconsistent for those patients with multiple admissions, appearing, for the same patient, in one admission but not others; those with inconsistent documentation of chronic pain were substantially more likely to self-discharge. 

PainRelief.com: What should readers take away from your report?

Response: These findings underscore the importance of aggressive and effective pain care in disrupting a process of self-directed discharge, intensifying harm, and preventable financial cost and suffering. Each admission represents a potential opportunity to provide harm reduction and treatment interventions addressing both substance use and pain.  

PainRelief.com: What recommendations do you have for future research as a result of this work?

Response: Future research should be aimed at evaluating approaches for effective pain management in patients with opioid related disorders.  These patients may present with high levels of opioid analgesic tolerance and opioid-induced hyperalgesia, suggesting that non-opioid analgesic approaches may be warranted to effectively manage their pain.  Regardless of the specific pain management approach employed, patients with opioid-related disorders should believe that their complaints of pain are taken seriously and managed aggressively to maximize duration of hospital stay.

Citation:

Compton, P., Aronowitz, S.V., Klusaritz, H. et al. Acute pain and self-directed discharge among hospitalized patients with opioid-related diagnoses: a cohort study. Harm Reduct J 18131 (2021). https://doi.org/10.1186/s12954-021-00581-6

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Acupuncture for Pain Relief: Insurance Coverage Increasing But Most Still Self Pay

PainRelief.com Interview with:
Molly Candon, PhD
Research Assistant Professor, Center for Mental Health, Department of Psychiatry
Assistant Professor, Department of Health Care Management
Director, Associate Fellows Program, Leonard Davis Institute of Health Economics
Perelman School of Medicine and the Wharton School
University of Pennsylvania

Molly Candon, PhD Research Assistant Professor, Center for Mental Health, Department of Psychiatry Assistant Professor, Department of Health Care Management Director, Associate Fellows Program, Leonard Davis Institute of Health Economics Perelman School of Medicine and the Wharton School University of Pennsylvania
Dr. Candon

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

Response: Insurance design for pain care, including whether treatments are covered and how generously they are covered, is an important element of access and adherence. Acupuncture therapy is a safe and evidence-based treatment for numerous pain conditions, and our team was curious if acupuncture coverage has changed in recent years given the need for non-opioid treatments during the ongoing opioid epidemic. 

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Older Adult Black Men at Disproportionate Risk of Fatal Opioid Overdose

PainRelief.com Interview with:
Maryann Mason, PhD
Department of Emergency Medicine
Northwestern University Feinberg School of Medicine
Buehler Center for Health Policy and Economics,
Northwestern University, Chicago, Illinois

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

Response: This study came about because we were looking at data for Cook County, Illinois and saw an increase in older adult opioid overdose deaths.  That made us wonder if there was a national trend or the observation was limited to our local area.  We undertook the research to determine that and found that it is indeed a national phenomenon.

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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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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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