US Pharm. 2024;49(3):29-33.


Mixed News for People With Low Back Pain

Low back pain is a major cause of disability around the globe, with more than 570 million people affected. In the United States alone, healthcare spending on low back pain was $134.5 billion between 1996 and 2016, and costs are increasing.

“The good news is that most episodes of back pain recover, and this is the case even if you have already had back pain for a couple of months,” said Lorimer Moseley, a professor with the University of South Australia.

“The bad news is that once you have had back pain for more than a few months, the chance of recovery is much lower. This reminds us that although nearly everyone experiences back pain, some people do better than others, but we don’t completely understand why.”

The systematic review and meta-analysis, conducted by an international team of researchers, included 95 studies with the goal of understanding the clinical course of acute (<6 weeks), subacute (6 to <12 weeks), and persistent (12 to <52 weeks) low back pain. For people with new back pain, pain and mobility problems lessened significantly in the first 6 weeks, but then recovery slowed.

This study filled a gap in a 2012 paper from the same research team, with new findings showing that many people with persistent low back pain (>12 weeks) continue to have moderate-to-high levels of pain and disability. “These findings make it clear that back pain can persist even when the initial injury has healed,” Dr. Moseley said.

“In these situations, back pain is associated with pain system hypersensitivity, not ongoing back injury. This means that if you have chronic back pain—back pain on most days for more than a few months—then it’s time to take a new approach to getting better.”

He noted that there are new treatments based on training both the brain and body that “focus on first understanding that chronic back pain is not a simple problem, which is why it does not have a simple solution, and then on slowly reducing pain system sensitivity while increasing your function and participation in meaningful activities.”

The authors stated that identifying slowed recovery in people with subacute low back pain is important so that care can be escalated and the likelihood of persistent pain reduced.

Further research into treatments is needed to help address this common and debilitating condition and to better understand it in people aged younger than 18 years and older than 60 years.


Injectable Electrodes May Enable Painless Arrhythmia Treatment

A study led by Mehdi Razavi at the Texas Heart Institute (THI), in collaboration with a biomedical engineering team of the University of Texas at Austin (UT Austin) Cockrell School of Engineering led by Elizabeth Cosgriff-Hernandez, sets the foundation for a new regimen for treating ventricular arrhythmia. Their study, published in Nature Communications, demonstrates the design and feasibility of a new hydrogel-based pacing modality.

The urgent need for an effective therapeutic regimen for ventricular arrhythmia inspired THI’s Electrophysiology Clinical Research & Innovations team, led by its director, Dr. Razavi, to partner with Dr. Cosgriff-Hernandez and her UT Austin Biomedical Engineering team to codevelop a strategy that addresses the pathophysiology of re-entrant arrhythmia.

Ventricular arrhythmia, which occurs in the lower chambers of the heart, or ventricles, is the leading cause of sudden cardiac death in the United States. When heart rhythm abnormality occurs in a self-sustained manner, it is called re-entrant arrhythmia, which is usually fatal.

“Re-entry occurs mainly from delayed conduction in scarred heart tissues, usually after coronary artery occlusion during a heart attack, which can be corrected by enabling pacing in these regions,” said Dr. Razavi, a practicing cardiologist and cardiac electrophysiologist. “These hydrogels then can access the scarred tissue, thereby enabling direct pacing of the otherwise inaccessible regions of the heart.”

Given hydrogels’ biostability, biocompatibility, and tunable properties and the ease of incorporating electrical conductivity, the scientists are exploring them as potential electrodes that can be easily delivered inside coronary veins. A clinical advantage of the unique system is that ischemia can be avoided by delivering the hydrogel using the veins.

The researchers successfully deployed the innovative hydrogel technology through minimally invasive catheter delivery in a pig model. “The hydrogels have significant conductive properties that enable simultaneous pacing from multiple sites along the length of the hydrogel and create a conduction highway similar to those in Purkinje fibers,” according to Dr. Cosgriff-Hernandez.

Arrhythmia is treatable with medicines and procedures that control the irregular rhythms. The current antiarrhythmic drugs are not always effective; although the drugs slow the conduction velocity, they facilitate re-entry arrhythmia. Moreover, these drugs can be toxic and can lead to the destruction of tissues near the diseased regions of the heart. Even with the widely used interventional ablation therapies, arrhythmia recurs in a significant proportion of patients.

None of these procedures address the mechanism of re-entry.

Cardiac defibrillators implanted to compensate for the shortfalls in the current therapy options are painful when delivering electric shocks to restore heart rhythm and can severely deteriorate the patient’s quality of life. Left untreated, arrhythmia can damage the heart, brain, or other organs, leading to stroke or cardiac arrest, during which the heart suddenly and unexpectedly stops beating.

“When injected into target vessels, the conductive hydrogel conforms to the patient’s vessel morphology. Adding a traditional pacemaker to this gel allows for pacing that resembles the native conduction in the heart—effectively mimicking the native electrical rhythm of the heart—and extinguishes the cause for arrhythmia, providing painless defibrillation,” added Dr. Cosgriff-Hernandez.

The work demonstrates for the first time the ability to confer direct electrical stimulation of the native and scarred mid-myocardium through injectable hydrogel electrodes as a pacing modality. With minimally invasive catheter delivery and standard pacemaker technologies, this study indicates the feasibility of a novel pacing modality that resembles native conduction, potentially eliminating lethal re-entrant arrhythmia and providing painless defibrillation. The scientific advance is significant, considering that pain management is highly relevant to overall wellness for patients with heart, lung, and blood diseases.


Pain-Based Weather Forecasts Could Influence Actions

For individuals who experience chronic pain, weather can be a significant factor in their day-to-day plans. In a recent study from the University of Georgia, about 70% of respondents said they would alter their behavior based on weather-based pain forecasts.

“We’re finding more consistent relationships between weather patterns and pain, so it seems more possible to make weather-based pain forecasts,” said lead author and geography/atmospheric sciences lecturer Christopher Elcik. “This study was to survey and see what the audience was for this type of forecast.”

The study surveyed more than 4,600 individuals; among migraine sufferers, 89% identified weather as something that impacts their pain level, and 79% saw weather as a trigger for pain. Among those with other conditions, 64% said weather patterns could trigger pain, and 94% identified weather as a factor that impacts pain.

Dr. Elcik built on previous research regarding specific weather patterns and pain-related conditions to gauge public interest in a weather-based pain forecast, which could indicate high or moderate risk for migraines or chronic pain. “I see how much people can be affected by these types of pain, so if I can provide someone with insight into the level of risk for a day, maybe people can take steps to prevent the pain from happening,” he said. “There are preventative measures people can take if risks are higher.”

If the hypothetical risk was high, more than half of respondents said they were likely to take preventive measures, such as medication, resting, or avoiding compounding triggers, and about 47% of respondents with migraines and 46% with pain-related conditions were “extremely likely” to take such measures.

Desire for a forecasting tool was quite high, Dr. Elcik said, with 72% of those living with migraine and 66% with other pain-related conditions saying they would alter their behavior by canceling plans or taking preventive measures in response to a weather-based pain forecast.

Some respondents reported already using Web-based tools, such as AccuWeather’s arthritis or migraine forecast, which predicts low-to-high risk according to atmospheric conditions. With existing tools, however, there is little available information about the variables considered or how the predictions are made.

Likelihood to continue with plans also depended on the length of the activity. If plans were about 30 minutes long, 57% of respondents with migraines and 52% with other pain-related conditions said they were “extremely likely” to continue plans despite a moderate risk of pain, and about 43% from each group would continue with a highest risk forecast.

With an activity lasting more than 3 hours, however, that number dropped to around 23% for moderate risk and 18% for high risk with migraines and 21% or 23%, respectively, for other pain-related conditions. As level for risk increased, so did the likelihood to alter plans. “This was across the board,” Dr. Elcik said. “Everyone was more likely to cancel plans if the forecast risk was higher.”

While additional research and studies are needed to create a reliable pain-based weather forecast, Dr. Elcik said that this study highlights the importance of developing such a resource. “This publication shows there’s an audience that’s willing and eager to try something new, and there are probably many more people who would benefit—more than we even thought,” he said. “I think these results can push other researchers to also look at similar, larger-scale weather phenomena and help the community better understand how the atmosphere does impact pain,” he added.


Average of 22 U.S. Adolescents Died Weekly From Overdoses in 2022

An average of 22 adolescents aged 14 to 18 years died in the United States each week in 2022 from drug overdoses, raising the death rate for this group to 5.2 per 100,000. The increase was driven by fentanyl in counterfeit pills, new research finds.

Adolescent overdoses had more than doubled among this group between 2019 and 2020 and have since intensified to such an extent that the death count equals a high school classroom each week. It is now the third largest cause of pediatric deaths behind firearm-related injuries and motor vehicle collisions.

The increase is, however, not due to more illicit drug use, which has fallen over the years. For example, excluding cannabis, the rate of any illicit drug use among 12th graders had fallen from about 21% to 8% in the 20 years since 2002. Instead, the rise in overdoses is the result of drugs becoming deadlier due to fentanyl, which is increasingly found in counterfeit oxycodone, benzodiazepines, and other prescription pills that fall into the hands of adolescents.

Educators, physicians, and mental health practitioners can be instrumental in helping to stem this tide through pointed questions and guidance about drug use and the dangers that counterfeit pills present, researchers wrote in a paper published in the New England Journal of Medicine. In addition, policymakers can focus on “hotspot” counties, mostly in Western states, with particularly high overdose deaths.

“Teenagers are likely to be unaware of just how high-risk experimenting with pills has become, given the recent rise in counterfeit tablets,” said study coauthor Joseph Friedman, a researcher at the University of California, Los Angeles.

“It’s often impossible to tell the difference with the naked eye between a real prescription medication obtained from a doctor and a counterfeit version with a potentially deadly dose of fentanyl. It’s urgent that teenagers be given accurate information about the real risks and strategies to keep themselves and their friends safe.”

The researchers found that adolescent overdoses were occurring at double the national average in Arizona, Colorado, and Washington State between 2020 and 2022. They identified 19 hotspot counties—that is, those with at least 20 overdose deaths and death rates higher than the national average, with Maricopa County in Arizona and Los Angeles County having the most fatal overdoses at 117 and 111, respectively, during this period.

In addition, American Indian and Alaska Native adolescents had 1.82 times the overdose rates of whites between 2020 and 2022. Adolescents are overall likelier to use the pill form of the drug rather than powder, which was previously the main fentanyl source.

For instance, while 0.3% of high school seniors in 2022 reported using heroin, which comes in powder form, 5% reported nonmedical use of prescription pills the same year.

The researchers provided the following recommendations, among others, to combat these trends: 1)Pediatricians, other primary care physicians, and mental health practitioners should ask their adolescent patients if they or their peers were approached either in person or via social media about buying pills, or if they have used them without prescriptions;  2) educators, along with parents, can discuss with adolescents the dangers associated with counterfeit pills, with these efforts especially prioritized in hotspot locations; and 3) clinicians, educators, and parents can highlight the Safety First curriculum that emphasizes abstinence from drugs and provides information about risk reduction for those who do experiment with drugs, such as where to find and how to use the overdose-reversal agent naloxone.

In addition, the researchers recommended that naloxone be made available in schools, which should also adopt “no-questions-asked” pill-disposal programs, as well as provide anonymous mechanisms such messaging services that students can use to ask about counterfeit pills and substance use without risk of punishment or embarrassment.

“Fentanyl has rapidly become a leading cause of death in American teens,” said Scott Hadland, chief of adolescent medicine at Mass General for Children and senior author on the paper. “Policymakers, clinicians, families, and communities need to partner together to address this worsening public health threat.”


Childhood Trauma Increases Risk of Chronic Pain in Adulthood

Physical, sexual, or emotional abuse or neglect, either alone or combined with other types of childhood trauma, increases the risk of chronic pain and related disability in adulthood, according to new research.

These findings underscore the urgency of addressing adverse childhood experiences (ACEs)—potentially traumatic events that occur before age 18 years—and taking steps to mitigate their long-term impact on people’s health.

The study reviews research carried out across 75 years, involving 826,452 adults. Published in European Journal of Psychotraumatology, it reveals that individuals who have been exposed to various forms of traumatic events in childhood are at an increased risk of experiencing chronic pain and pain-related disability in adulthood, particularly among those subjected to physical abuse. The cumulative impact of exposure to multiple ACEs further exacerbates this risk.

“These results are extremely concerning, particularly as over 1 billion children—half of the global child population—are exposed to ACEs each year, putting them at increased risk of chronic pain and disability later in life,” said lead author André Bussières from the School of Physical and Occupational Therapy at McGill University in Montreal.

“There is an urgent need to develop targeted interventions and support systems to break the cycle of adversity and improve long-term health outcomes for those individuals who have been exposed to childhood trauma,” he said.

ACEs may affect a child or teenager directly through physical, sexual, or emotional abuse or neglect, or indirectly through exposure to environmental factors like domestic violence, living with substance abuse, or parental loss. Chronic pain, affecting between one-third and one-half of the United Kingdom population alone, is one of the leading causes of disability worldwide. Long-term painful conditions, such as low back pain, arthritis, headache, and migraine, can affect a person’s daily functioning to the point that they cannot work, eat properly, or participate in physical activities.

Previous research has indicated a positive relationship between exposure to ACEs and chronic pain in adulthood. However, there are still gaps in knowledge, particularly around which types of ACEs are associated with specific pain-related conditions or whether a dose-response relationship exists.

To help address these gaps, the authors carried out a systematic review that included 85 studies. Of those, results from 57 studies could be pooled in meta-analyses. They found that individuals exposed to a direct ACE, whether physical, sexual, or emotional abuse or neglect, were 45% more likely to report chronic pain in adulthood compared with those who were not exposed; childhood physical abuse was associated with a higher likelihood of reporting both chronic pain and pain-related disability; the odds of reporting chronic pain or pain-related disability in adulthood increased with exposure to any direct ACE, either alone or combined with indirect ACEs; and the risk of reporting chronic pain in adulthood significantly increased from exposure to one ACE to four or more ACEs.

“These results underscore the urgency of addressing ACEs, particularly in light of their prevalence and health repercussions,” said the senior author Professor Jan Hartvigsen from the University of Southern Denmark.

“A more nuanced understanding of the precise relationship between ACEs and chronic pain will empower healthcare professionals and policymakers to devise targeted strategies to help diminish the long-term impact of early-life adversity on adult health.”

The authors proposed that future research should delve into the biological mechanisms through which ACEs affect health across the lifespan, aiming to deepen understanding and develop ways to mitigate their impact.


Different MS Pain Types Can Make Staying Active Challenging

For patients with multiple sclerosis (MS), a regular exercise routine is important for managing symptoms. Due to different causes of chronic pain, though, physical exercise can be more difficult for some.

Research published in the Journal of Pain from the University of Michigan found that widespread pain with nociplastic features (WPNF) can make engaging in physical activity a painful task for some patients with MS.

“WPNF is a chronic and diffuse pain which can be challenging to localize or describe precisely,” said Libak Abou, PhD, research assistant professor and lead author of the paper.

“In a person with MS, this type of pain arises from altered processing signals within the central nervous system. This is opposed to pain that arises from specific tissue damage, classified as nociceptive pain, or pain related to demyelination and axonal damage, classified as neuropathic pain,” he said.

Dr. Abou and fellow researchers surveyed patients with MS to see if those with a higher indication of WPNF were more likely to be insufficiently active or sedentary when compared with their MS counterparts with no chronic pain, nociceptive pain, or neuropathic pain.

Each of the participants self-reported their data. The results of the survey showed that those who experienced WPNF in addition to their MS were not sufficiently active due to the chronic pain they were experiencing.

“There is a growing need to consider what type of pain MS patients are experiencing before giving them an exercise plan,” said Dr. Abou. “The concept of considering WPNF when creating exercise plans for MS is newer but could help many patients get to an activity level that will help ease symptoms without causing them intense pain.”

In the future, Dr. Abou hopes that clinicians can begin doing screenings for underlying pain mechanisms in patients with MS who are struggling to stay active to help further tailor their physical routines to their personal needs. “The end goal is to help those with MS maintain their functional independence,” he said. “It is also important to remember that these patients will likely need extra support from their physical therapy team to keep them on a path with less pain.”

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