Acetaminophen (paracetamol) During Pregnancy May Alter Fetal Development

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PainRelief.com Interview with:
Ann Z. Bauer ScD
Department of Work Environment
University of Massachusetts Lowell | UML 

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

Response: Acetaminophen (paracetamol, brand name Tylenol) is an over-the-counter medication used to relieve pain and reduce fever. It is an active ingredient in over 600 medications and used by more than 50% of pregnant women worldwide and up to 65% of pregnant women in the US.

Current guidance recommends acetaminophen as the pain reliever of choice during pregnancy, as other pain relievers such as ibuprofen and aspirin are contraindicated during pregnancy, particularly after 20 weeks.

In this consensus statement the authors reviewed the research on acetaminophen use during pregnancy from 1995 through 2020 and found a growing body of evidence that suggests prenatal acetaminophen exposure may alter fetal development increasing the risk of neurodevelopmental, reproductive and urogenital disorders. Importantly, this review identifies a convergence of evidence from the trifecta of research areas -human cohort studies, in vitro and animal models. This statement asking for precaution and more research was supported by a total of 91 clinicians and researchers (13 authors and 78 signatories) from around the world.

Research suggests acetaminophen is an endocrine disruptor meaning it interferes with the proper functioning of hormones, specifically it is an anti-androgen that can significantly reduce testosterone production.  Acetaminophen exposure during pregnancy has been suggested to increase the risk of male undescended testicles (cryptorchidism) and shorter anogenital distance (ADG) a marker of sub-fertility.  Additionally, research suggests increased risk of neurodevelopmental disorders primarily attention deficit hyperactivity disorder (ADHD) and related behavioral abnormalities, but also autism spectrum disorder (ASD), language delays, decreased IQ, and conduct disorders.

Many users do not consider acetaminophen to be a medication with potential side effects. There is high usage, in part, because of a perception  that use is of negligible risk.  However, because use is so common, if acetaminophen is responsible for even a small increase in individual risk it could contribute substantially to these disorders in the overall population.

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Migraine Pain Linked to Stress Varies by Individual

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PainRelief.com Interview with:

Serena L. Orr, MD, MSc, FRCPC, FAHS
Assistant Professor
Depts of Pediatrics, Clinical Neurosciences and Community Health Sciences 
Cumming School of Medicine, University of Calgary
Director, Pediatric Headache Program
Alberta Children’s Hospital

Dr. Orr

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

Response: Stress has long been felt to be one of the most common trigger factors for migraine. However, there is very little data on the relationship between stress and pain severity in individuals with migraine on a day-to-day basis, and this relationship is even more poorly understood among individuals with more frequent attacks, such as those with chronic migraine (who have at least 15 days/month of headache, 8 or more of which meet criteria for migraine attacks).

This was a study that looked at daily electronic headache diary data for 136 adults with chronic migraine, using data from the N1-Headache application. In this study, we aimed to understand the relationship between perceived stress and pain severity in individuals with chronic migraine. Individuals completed 90 days of daily diary entries where they reported on their headache characteristics, and their perceived stress levels, measured on a scale of 0-10.

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Caution Should Be Taken with Hip Steroid Injections For Arthritis Pain Relief

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PainRelief.com Interview with:
Kanu M. Okike, MD
Orthopedic Surgeon
The Hawaii Permanente Medical Group

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

Response: Hip corticosteroid injections are a common treatment for osteoarthritis and other hip conditions.  Recently, isolated case reports have raised the question of whether hip corticosteroid injections could be associated with rapid progression of the arthritis process – a condition known as rapidly destructive hip disease (RDHD).

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Pain Relief Study of Low Carb Ketogenic Diet

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PainRelief.com Interview with:
Rowena Field
B.App.Sc (phty) M.Physio. APAM
Physiotherapist/Director
PhD research candidate Sydney University
STEPP (solutions tools and education for persistent pain)

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

Response: Chronic pain is a difficult problem to treat because it is multifactorial, driven by the brain continuing to arrive at the conclusion that protection is required. Turning up the sensitivity in the nervous system results in ongoing pain as a protector even though there is no new tissue damage. Other protection mechanisms such as increased inflammation, and increased sympathetic ‘fight or flight’ also occur.

Chronic pain becomes part of a whole system protective response, so looking at other treatment options that alter the system (such as diet) are useful additions to pain management. A ketogenic diet restricts carbohydrate to below 50g/day producing ketones for energy from fat. It has been used to treat epilepsy over the last two centuries and successfully reduces nervous system excitability. Many of the drugs used for chronic pain (such as Lyrica) are also anti-epileptic medications, suggesting common pathways. As well as these impacts on the nervous system, pre-clinical research has also shown ketones to be signalling molecules that reduce inflammation.

Combined with the clinical reports that pain reduction occurred when people were on ketogenic diets, it seemed reasonable to test the diet specifically in a chronic pain population.

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Switching to Buprenorphine Might Provide Pain Relief for Poorly Controlled Pain

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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.

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Knee Arthritis: Racial Differences in Treatment Patterns and Health Care Expenditures

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PainRelief.com Interview with:
Stuart L. Silverman MD FACP FACR
Clinical Professor of Medicine, Cedars-Sinai Medical Center and UCLA School of Medicine
Medical Director, OMC Clinical Research Center
Beverly Hills, CA 90211

Dr. Silverman

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

Response: As a practicing rheumatologist, I am aware that prior studies have shown variation in medical care, pain management and treatment with opioids by race and social economic status.  Suboptimal treatment of pain in patients with osteoarthritis (OA) may also disproportionately burden racial minorities and Medicaid recipients. 

Studies have shown that African Americans are nearly 1.5 times as likely to have symptomatic knee OA than White patients even when adjusting for other factors.  Similarly, they also have a higher prevalence of symptomatic and radiographic hip OA.  Analyses of Medicare data has shown evidence of persistent racial disparities for joint arthroplasty usage and surgical outcomes.

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

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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.

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Physicians Differently Prescribe Pain Relief Medications to White and Minority Patients

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PainRelief.com Interview with:
Dan P. Ly M.D., M.P.P., Ph.D.
Division of General Internal Medicine and Health Services Research
David Geffen School of Medicine
University of California, Los Angeles

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

Response: We know that minority patients were less likely to receive opioids than white patients, but this could have been due to minority patients seeing lower opioid-prescribing physicians. As far as I could tell, nobody had been able to examine whether the same physician prescribed opioids differently to their minority patients.

I find that this is the case: the same physician was less likely to prescribe opioids to their minority patients with new low back pain, and instead was more likely to prescribe NSAIDs to their minority patients. And unfortunately, this differential prescribing may have had the consequence of leading to more chronic opioid use in white patients.  

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Medlab Clinical Developing New Buccal Spray for Chronic Cancer Pain Relief

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PainRelief.com Interview with:
Dr.  Jeremy Henson
Director of Medical Affairs
Medlab Clinical Ltd

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

Response: THC and CBD combination medicines have the potential to provide a non-opioid option for chronic pain that does not have the GIT or respiratory adverse reactions of opioids and allows better cognitive functioning.

Delivery across the oro-buccal membrane appears to be best method of administration of cannabinoids for chronic pain. Oro-buccal delivery has pharmacokinetics appropriate for 6-8 hourly maintenance dosing and avoids first pass metabolism and the slow erratic onset of ingestion; and the high serum THC peaks, frequent redosing and toxic oxidation products of vaping.

The problems with using a 50% ethanol vehicle to deliver cannabinoids across the oro-buccal membrane include local irritation, incomplete absorption and significant systemic ethanol levels. These issues could be solved by using a micellular nanoparticle to solubilise the cannabinoids and deliver them across the oro-buccal mucous membrane.

This study was a first in human study of a micellular nanoparticle formulation of 1:1 THC and CBD delivered as an oro-buccal spray for chronic cancer pain.

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Virtual Reality Can Provide Pain Relief for Children Getting IV Catheters

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PainRelief.com Interview with:
Dr. Jeffrey I. Gold PhD
Director Emeritus of the Pediatric Pain Medicine Clinic
Children’s Hospital Los Angeles and Investigator
The Saban Research Institute
Children’s Hospital Los Angeles

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

Response: Virtual Reality or digital therapeutics can have a profound impact on mitigating pain, anxiety, and distress associated with routine painful medical procedures, such as blood draw and IV placement. 

PainRelief.com:  What are the main findings? Would you explain what is meant by “triangulation of data”?

Response: Virtual Reality significantly reduces pain and anxiety in children undergoing PIVC placement compared to standard of care in two pediatric medical settings (radiology and the infusion center). The triangulation of data refers to collecting data on the patient, his/her caregiver, and the healthcare provider to examine the impact of the intervention from three different perspectives.

The current study demonstrated that an effective intervention for the patient can have a positive impact (ripple effect) on the caregiver and the healthcare provider, creating a more relaxed, calm, and less distressing medical experience.

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