Experimental “bitopic” Opioid Suppresses Pain With Fewer Side Effects

PainRelief.com Interview with:

Susruta Majumdar, PhD
Professor in the Department of Anesthesiology
Washington University School of Medicine
Nokomis Ramos-Gonzalez, PhD
Postdoctoral Trainee in the Majumdar Lab
Washington University School of Medicine
Balazs R. Varga PhD
Center for Clinical Pharmacology
University of Health Sciences & Pharmacy at St. Louis
Department of Anesthesiology and Washington University Pain Center
Washington University School of Medicine
St. Louis, Missouri 63110

Jay McLaughlin, Ph.D
Professor of Pharmacodynamics
College of Pharmacy
University of Florida

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

Response:    Opioid medications tap into the body’s natural system for mitigating pain by activating pain-suppressing opioid receptors on neurons. Although meant to help, sometimes these medications do harm.  Opioid medications offer people relief from debilitating pain, but these drugs come with dangers: the risk for addiction, miserable withdrawal symptoms and the potential for fatal overdose.  New mechanistic insights into the function and regulation of the opioid receptors present the opportunity to design new, safer opioid painkillers. The team’s previous research utilized a strategy to design functionally selective “bitopic” opioids by targeting the sodium binding allosteric site in the opioid receptor.

Gene Linked to Efficacy of Gabapentin for Chronic Pelvic Pain Identified

PainRelief.com Interview with:
Dr Lucy ​H R Whitaker (BSc (Hons) MB ChB MSc MD MRCOG)
Senior Clinical Research Fellow and Honorary Consultant Gynaecologist
Centre for Reproductive Health,
Institute for Regeneration and Repair 
Edinburgh BioQuarter 
Edinburgh 

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

Response: Our study focused on chronic pelvic pain in women, a common condition affecting up to one in four women, for which there are few evidence-based treatment options. We previously conducted a multicentre randomised controlled trial (GaPP2) to assess the effectiveness of gabapentin, a commonly prescribed painkiller, in relieving chronic pelvic pain.

The trial found that gabapentin did not relieve pain and was associated with more side effects compared to a placebo. However, to better understand why some women respond to gabapentin more than others, we studied the DNA of the participants from the GaPP2 trial to identify genetic changes that might affect response to gabapentin.

Fibromyalgia: Smartphone Delivered CBT Therapy Reduced Symptoms and Enhanced Well-Being

PainRelief.com Interview with:
Mike Rosenbluth, PhD
CEO, Swing Therapeutics
UCSF Rosenman Innovators Program
San Francisco, CA

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

Response: Fibromyalgia is a chronic pain condition that affects an estimated 10 million Americans, characterized by widespread pain and other physical and cognitive symptoms that include fatigue, disrupted sleep, reduced physical function, memory problems and difficulty concentrating (“brain fog”). Clinical guidelines recommend multimodal treatment that combines medication management with non-drug approaches including cognitive behavioral therapy (CBT), but only 5% of fibromyalgia patients annually end up receiving some form of CBT due to lack of trained providers or cost. 

There have been dozens of studies on CBT for management of chronic pain or fibromyalgia specifically. The majority of these studies are small, are testing an intervention that cannot scale, and are run at a single site. These studies ultimately conclude that more research should be done. We aimed to develop a product that could deliver behavioral therapy for fibromyalgia at scale and test that product in a rigorous study that was powered to demonstrate definitive clinical benefit of the treatment.

Stanza is a self-guided, smartphone-based digital therapy that delivers acceptance and commitment therapy (ACT), a type of CBT.  In this multi-center, randomized controlled trial, 275 participants were randomized to receive either Stanza treatment or an active control intervention (in this case a digital symptom tracker and access to health education). 

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CMAJ Study Suggests Clinicians Adapt Opioid Prescriptions to Specific Types of Acute Pain

PainRelief.com Interview with:
Raoul Daoust MD CSPQ MSc
Professeur titulaire/ full professor
Département Médecine de Famille et Médecine d’Urgence
Université de Montréal
Clinicien chercheur / Clinician Researcher
Médecine d’Urgence / Emergency Medicine
CEMU-HSCM (Centre d’Étude en Médecine d’Urgence)
SCEM-HSCM (Study Center in Emergency Medicine)
Hôpital Sacré-Coeur de Montréal
CIUSSS Nord-de-l’ile

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

Response: Overprescribing is linked to opioid misuse and overdose, with household supplies of opioids associated with an increased risk of overdose as many people do not dispose of unused medications safely. In Canada, more than 7570 people died of opioid overdoses in 2021, and more than 68 000 people died in the United States in 2020 from these same drugs.

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Chronic Pain Conditions Among Women in the Military Health System

PainRelief.com Interview with:
Andrew J. Schoenfeld, MD
Professor, Harvard Medical School
Orthopaedic Surgery
Brigham and Women’s Hospital 

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

Response: The impetus for this research stems from my time as the Director of the Medical Evaluation Board at Fort Bliss Texas during my time on active duty with the Army between 2009-13 and my time in Ann Arbor VA between 2013-15.  We wanted to understand the impact that repeated exposure to the high intensity deployment to combat theaters during 2006-2013  had on women active duty servicemembers and women civilian dependents of active duty servicemembers who were deploying

PainRelief.com: What are the main findings?

Response: Significant increases in the diagnosis of Chronic Pain conditions among women active duty service members as well as women civilian dependents who were affiliated with the military between 2006-13.

WalkBack Trial: Simple Exercise Strategy plus Education Can Help Prevent Recurrence of Low Back Pain

PainRelief.com Interview with:
Natasha C Pocovi
Department of Health Sciences
Macquarie University, Sydney
NSW, Australia

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

Response: Approximately 620 million people globally, reported suffering low back pain in 2020. While it’s not considered a life-threatening disease, we can see the very serious impacts it can have on people’s lifestyle, ability to work, and overall quality of life. While much work is being done to treat low back pain, ‘prevention’ is mostly unchartered territory. This is particularly important given the high rates of recurrent low back pain, where 7 in 10 people who recover from an episode of low back pain will have a new episode in the next 12 months.

A small number of studies have examined exercise to prevent the recurrence of low back pain. These have primarily focused on group-based, complex exercises focusing on a combination of strengthening and improving the endurance and flexibility of the spine. Some of these were delivered over several supervised sessions, some as many as 20 x 1-hour sessions. This becomes less feasible for patients to engage in.

EULAR 2024: Non-Articular Pain Common in Patients with Rheumatoid Arthritis

PainRelief.com Interview with:

Charis F. Meng, MD
Rheumatologist, Inflammatory Arthritis Center
Assistant Attending Physician
Hospital for Special Surgery
Assistant Professor of Clinical Medicine
Weill Cornell Medical College

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

Response: Non-articular pain (NAP) is common in our patients with rheumatoid arthritis (RA) and may impact remission outcomes.  However, it is challenging for busy rheumatologists to address specific pain types in our patients with RA, as it is not well defined in the literature, nor has it been validated in RA.  NAP in RA care thus is an unmet need for both our patients with RA and rheumatologists caring for them. 

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Pain Perception May Occur Differently in Men and Women

PainRelief.com Interview with:
Frank Porreca, PhD
Associate Department Head, Pharmacology
Member of the Graduate Faculty
Professor, Anesthesiology
Professor, Cancer Biology – GIDP
Professor, Neuroscience – GIDP
Professor, Pharmacology
College of Medicine
University of Arizona

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

Response: Our research concerns the mechanisms that initiate perception of pain rather than the experience of pain itself. 

Pain commonly results from activation of sensory fibers called nociceptors.  Nociceptors normally are activated by high intensity stimuli (e.g., like touching a hot stove) but not by low intensity stimuli (like touch itself). But, when there is an injury like a mild inflammation such as a sunburn, then light touch like the rubbing of your shirt on your sunburned neck can produce activation of nociceptors and the perception of pain.  This indicates that the thresholds for activation of the nociceptors has decreased so that normally innocuous stimuli can now result in pain.  The mechanisms by which the thresholds for activation of nociceptors are decreased are important as this can promote instances of pain from normally nonpainful stimuli, movement of joints, migraine, irritable bowel syndrome, temporomandibular disorder etc… 

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Cannabis Components Terpenes Tested for Neuropathic Pain

PainRelief.com Interview with:
John M. Streicher, PhD
Member of the Graduate Faculty
Professor, Neuroscience – GIDP
Professor, Pharmacology
College of Medicine, Tucson
University of Arizona

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

Response: Cannabis has many chemical components that have potential therapeutic benefits, however, the great majority of research to date has focused on the major cannabinoids THC and CBD. In the past, different groups have tested the pharmacological effects of terpenes, which are small aromatic compounds in Cannabis and other plants that impart taste and aroma. They found pain relieving and anti-inflammatory effects, in both pre-clinical and clinical studies. However, those studies mostly did not test the therapeutic aspects of terpenes like side effects and dosing routes, and the mechanism of action in pain is also mostly unclear.

We thus began our studies by comprehensively testing a set of 5 terpenes for their pharmacological and therapeutic effects. In 2021, we published a paper showing the terpenes had cannabinoid-like behavioral effects, and also worked through the Cannabinoid Receptor 1 and the Adenosine A2a Receptor to carry out these effects. We also found that they had stronger effects when combined with a cannabinoid.

Study Finds Liposomal Bupivacaine Alone Not Sufficient to Control Pain During Surgery

PainRelief.com Interview with:
Professor Peter Marhofer, MD
Director of Paediatric Anaesthesia
Senior Researcher Paediatric and Regional Anaesthesia
Medical University of Vienna
Department of Anaesthesia, Intensive Care Medicine and Pain Medicine
Vienna, Austria

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

Response: One of the major limitations in the use of local anaesthetics is their limited duration of action. In recent years, liposomal formulations with prolonged release kinetics have been developed with the idea to control the sensation of pain not only during but also after surgery and thus achieving an opioid-sparing effect. In this context “liposomal” means that the active ingredient is encapsulated in vesicles called liposomes, which should enable a slower release over a longer period of time. In our study we included 25 healthy volunteers. The study participants were randomly assigned to receive two nerve blocks with bupivacaine for pain control, one in the conventional and one in the liposomal form.

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