Female hormones can suppress pain by making immune cells near the spinal cord produce opioids, a new study from researchers at UC San Francisco has found. This stops pain signals before they get to the brain.
The discovery could help with developing new treatments for chronic pain. It may explain why some painkillers work better for women than men and why postmenopausal women, whose bodies produce less of the key hormones oestrogen and progesterone, experience more pain.
The work reveals an entirely new role for T regulatory immune cells (T-regs), which are known for their ability to reduce inflammation.
“The fact that there’s a sex-dependent influence on these cells – driven by oestrogen and progesterone – and that it’s not related at all to any immune function is very unusual,” said Elora Midavaine, PhD, a postdoctoral fellow and first author of the study, which appears in Science.
The researchers looked at T-regs in the protective layers that encase the brain and spinal cord in mice. Until now, scientists thought these tissue layers, called the meninges, only served to protect the central nervous system and eliminate waste. T-regs were only discovered there in recent years.
“What we are showing now is that the immune system actually uses the meninges to communicate with distant neurons that detect sensation on the skin,” said Sakeen Kashem, MD, PhD, an assistant professor of dermatology. “This is something we hadn’t known before.”
That communication begins when a neuron, often near the skin, receives a stimulus and sends a signal to the spinal cord.
The team found that the meninges surrounding the lower part of the spinal cord harbour an abundance of T-regs. To learn what their function was, the researchers knocked the cells out with a toxin.
The effect was striking: Without the T-regs, female mice became more sensitive to pain, while male mice did not. This sex-specific difference suggested that female mice rely more on T-regs to manage pain.
“It was both fascinating and puzzling,” said Kashem, who co-led the study with Allan Basbaum, PhD. “It actually made me sceptical initially.”
Further experiments revealed a relationship between T-regs and female hormones that no one had seen before: Estrogen and progesterone were prompting the cells to churn out enkephalin, a naturally occurring opioid.
Exactly how the hormones do this is a question the team hopes to answer in a future study. But even without that understanding, the awareness of this sex-dependent pathway is likely to lead to much-needed new approaches for treating pain.
In the short run, it may help physicians choose medications that could be more effective for a patient, depending on their sex. Certain migraine treatments, for example, are known to work better on women than men.
This could be particularly helpful for women who have gone through menopause and no longer produce oestrogen and progesterone, many of whom experience chronic pain.
The researchers have begun looking into the possibility of engineering T-regs to produce enkephalin on a constant basis in both men and women.
Patients prescribed medicinal cannabis in Australia maintained improvements in overall health-related quality of life (HRQL), fatigue, and sleep disturbance across a one-year period, according to a study published April 2, 2025, in the open-access journal PLOS One by Margaret-Ann Tait from The University of Sydney, Australia, and colleagues. Anxiety, depression, insomnia, and pain also improved over time for those with corresponding health conditions.
Research into the therapeutic benefits of medicinal cannabis has increased since the discovery of the analgesic properties in cannabis plant compounds. In 2016, advocacy groups lobbied the Australian government to bring about legislation changes that allow patients who were not responding to conventional treatment to access medicinal cannabis with a prescription from clinicians. More than one million new patients in Australia have received medicinal cannabis prescriptions for more than 200 health conditions.
A multicenter prospective study called the QUEST initiative (QUality of life Evaluation STudy) recruited adult patients with any chronic health condition newly prescribed medicinal cannabis oil between November 2020 and December 2021. Tait and colleagues gathered 12-month follow-up data to determine if previously reported improvements at three months would be maintained long-term. Of 2744 consenting participants who completed baseline assessments, 2353 also completed at least one follow-up questionnaire and were included in analyses, with completion rates declining to 778/2353 (38%) at 12 months. Participants with clinician-diagnosed conditions completed questionnaires covering condition-specific symptoms, and HRQL, which encompasses physical, emotional, social, and cognitive function, as well as bodily discomfort.
The researchers found that short-term improvements in overall HRQL reported at three months were maintained over a 12-month period in patients prescribed medicinal cannabis in Australia. People with chronic health conditions reported improvements in fatigue, pain, and sleep. Patients with anxiety, depression, insomnia, or chronic pain diagnoses also showed improvements in condition-specific symptoms over 12 months. Patients treated for generalized anxiety, chronic pain, insomnia, and PTSD all showed improvements in HRQL. Participants with movement disorders had improved HRQL but no significant improvements in upper extremity function scores.
The study was large enough to assess patients across a wide range of chronic conditions and socio-demographics in a real-world setting. However, without a control group, it was not possible to confidently attribute changes over time to medicinal cannabis.
Despite this limitation, the results suggest that prescribing medicinal cannabis to patients with chronic health conditions may improve pain, fatigue, insomnia, anxiety, and depression and overall HRQL. The findings also suggest that any improvements would be apparent quickly and maintained long-term. According to the authors, the results from this study contribute to the emerging evidence base to inform decision making both in clinical practice and at the policy level.
The authors add: “This is promising news for patients who are not responding to conventional medicines for these conditions.”
“It’s really sore,” my (Josh’s) five-year-old daughter said, cradling her broken arm in the emergency department.
“But on a scale of zero to ten, how do you rate your pain?” asked the nurse.
My daughter’s tear-streaked face creased with confusion.
“What does ten mean?”
“Ten is the worst pain you can imagine.” She looked even more puzzled.
As both a parent and a pain scientist, I witnessed firsthand how our seemingly simple, well-intentioned pain rating systems can fall flat.
What are pain scales for?
The most common scale has been around for 50 years. It asks people to rate their pain from zero (no pain) to ten (typically “the worst pain imaginable”).
This focuses on just one aspect of pain – its intensity – to try and rapidly understand the patient’s whole experience.
How much does it hurt? Is it getting worse? Is treatment making it better?
Rating scales can be useful for tracking pain intensity over time. If pain goes from eight to four, that probably means you’re feeling better – even if someone else’s four is different to yours.
But that common upper anchor in rating scales – “worst pain imaginable” – is a problem.
People usually refer to their previous experiences when rating pain. Photo by Rodnae Productions on Pexels
A narrow tool for a complex experience
Consider my daughter’s dilemma. How can anyone imagine the worst possible pain? Does everyone imagine the same thing? Research suggests they don’t. Even kids think very individually about that word “pain”.
People typically – and understandably – anchor their pain ratings to their own life experiences.
This creates dramatic variation. For example, a patient who has never had a serious injury may be more willing to give high ratings than one who has previously had severe burns.
“No pain” can also be problematic. A patient whose pain has receded but who remains uncomfortable may feel stuck: there’s no number on the zero-to-ten scale that can capture their physical experience.
In reality, pain ratings are influenced by how much pain interferes with a person’s daily activities, how upsetting they find it, their mood, fatigue and how it compares to their usual pain.
Other factors also play a role, including a patient’s age, sex, cultural and language background, literacy and numeracy skills and neurodivergence.
For example, if a clinician and patient speak different languages, there may be extra challenges communicating about pain and care.
Still, we work with the tools available. There is evidence people do use the zero-to-ten pain scale to try and communicate much more than only pain’s “intensity”.
So when a patient says “it’s eleven out of ten”, this “impossible” rating is likely communicating more than severity.
They may be wondering, “Does she believe me? What number will get me help?” A lot of information is crammed into that single number. This patient is most likely saying, “This is serious – please help me.”
In everyday life, we use a range of other communication strategies. We might grimace, groan, move less or differently, use richly descriptive words or metaphors.
Collecting and evaluating this kind of complex and subjective information about pain may not always be feasible, as it is hard to standardise.
As a result, many pain scientists continue to rely heavily on rating scales because they are simple, efficient and have been shown to be reliable and valid in relatively controlled situations.
But clinicians can also use this other, more subjective information to build a fuller picture of the person’s pain.
Visual scales are one tool. For example, the “Faces Pain Scale-Revised” asks patients to choose a facial expression to communicate their pain. This can be particularly useful for children or people who aren’t comfortable with numeracy and literacy, either at all, or in the language used in the health-care setting.
A vertical “visual analogue scale” asks the person to mark their pain on a vertical line, a bit like imagining “filling up” with pain.
Listen for the story behind the number, because the same number means different things to different people.
Use the rating as a launchpad for a more personalised conversation. Consider cultural and individual differences. Ask for descriptive words. Confirm your interpretation with the patient, to make sure you’re both on the same page.
Patients
To better describe pain, use the number scale, but add context.
Try describing the quality of your pain (burning? throbbing? stabbing?) and compare it to previous experiences.
Explain the impact the pain is having on you – both emotionally and how it affects your daily activities.
Paediatric health professionals are trained to use age-appropriate vocabulary, because children develop their understanding of numbers and pain differently as they grow.
A starting point
In reality, scales will never be perfect measures of pain. Let’s see them as conversation starters to help people communicate about a deeply personal experience.
That’s what my daughter did — she found her own way to describe her pain: “It feels like when I fell off the monkey bars, but in my arm instead of my knee, and it doesn’t get better when I stay still.”
From there, we moved towards effective pain treatment. Sometimes words work better than numbers.
This effect even occurs with virtual nature – such as nature videos
Photo by Sebastian Unrau on Unsplash
In a new study, an international team of neuroscientists led by the University of Vienna has shown that experiencing nature can alleviate acute physical pain. Surprisingly, simply watching nature videos was enough to relieve pain. Using functional magnetic resonance imaging, the researchers found that acute pain was rated as less intense and unpleasant when watching nature videos – along with a reduction in brain activity associated with pain. The results, published in Nature Communications, suggest that nature-based therapies can be used as promising complementary approaches to pain management.
“Pain processing is a complex phenomenon” explains study lead and doctoral student Max Steininger from the University of Vienna. In order to better understand it and identify treatment options, Steininger and his colleagues investigated how nature exposure influences pain: participants suffering from pain were shown three types of videos: a nature scene, an indoor scene, and an urban scene. The participants rated the pain while their brain activity was measured using functional magnetic resonance imaging. The results were clear: when viewing the nature scene, the participants not only reported less pain but also showed reduced activity in brain regions associated with pain processing.
By analyzing the brain data, the researchers showed that viewing nature reduced the raw sensory signal the brain receives when in pain. “Pain is like a puzzle, made up of different pieces that are processed differently in the brain. Some pieces of the puzzle relate to our emotional response to pain, such as how unpleasant we find it. Other pieces correspond to the physical signals underlying the painful experience, such as its location in the body and its intensity. Unlike placebos, which usually change our emotional response to pain, viewing nature changed how the brain processed early, raw sensory signals of pain. Thus, the effect appears to be less influenced by participants’ expectations, and more by changes in the underlying pain signals,” explains Steininger.
Claus Lamm, head of research in the group, adds: “From another ongoing study, we know that people consistently report feeling less pain when exposed to natural environments. However, the underlying reason for this has remained unclear – until now. Our study suggests that the brain reacts less to both the physical source and the intensity of the pain.”
The current study provides important information on how nature can help alleviate pain and highlights that nature-based therapeutic approaches can be a useful addition to pain treatment. The fact, that this effect was observed by simply watching nature videos suggests that taking a walk outdoors may not be necessary. Virtual nature – such as videos or virtual reality – appears to be effective as well. This opens up a wide range of possible applications in both the private and medical sectors, providing people with a simple and accessible way to relieve their pain.
The study was conducted at the University of Vienna in collaboration with researchers from the Universities of Exeter and Birmingham (UK) and the Max Planck Institute for Human Development.
Facial pain and discomfort related to the temporomandibular joint (TMJ) is the second-leading musculoskeletal disorder, after chronic back pain, affecting 8% to 12% of Americans. Current treatments for TMJ disorders are not always sufficient, leading researchers to further explore the vast nerve and vessel network connected to this joint – the second largest in the human body.
In a study published in December 2024 in the journal Pain, a research team led by Yu Shin Kim, PhD, associate professor at the The University of Health Science Center at San Antonio (UT Health San Antonio), observed for the first time the simultaneous activity of more than 3000 trigeminal ganglion (TG) neurons, which are cells clustered at the base of the brain that transmit information about sensations to the face, mouth and head.
“With our novel imaging technique and tools, we can see each individual neuron’s activity, pattern and dynamics as well as 3000 neuronal populational ensemble, network pattern and activities in real time while we are giving different stimuli,” said Kim.
When the TMJ is injured or misaligned, it sends out signals to increase inflammation to protect the joint. However, this signaling can lead to long-term inflammation of the joint and other parts of the highly connected nerve network, leading to chronic pain and discomfort. About 80% to 90% of TMJ disorders occur in women, and most cases develop between the ages of 15–50.
Activation at the cellular level
Previous animal studies observed behavioural changes related to pain, but this study was the first to record reactions at the cellular level and their activities. To see which portions of the nerve pathway respond to various types of pain, Kim’s team created different models of pain and observed the neuronal activity with high-resolution confocal imaging, which uses a high-resolution camera and scanning system to observe neurons in action.
The team discovered that during TMJ activation, more than 100 neurons spontaneously fire at the same time. Activation was observed in localised areas of the TMJ innervated to TG neurons. The localisation of this activation highlights the specific neural pathways involved in TMJ pain, offering deeper insight into how pain develops and spreads to nearby areas. The study is also the first to quantify the degree of TG neuronal sensitivity and network activities.
Potential link to migraine, headaches
Chronic TMJ pain in humans is often linked to other pain comorbidity such as migraines and other headaches. Kim’s team observed this crossover in the in vivo model as inflammation of TG neurons spread to the nearby orofacial areas. Kim’s previous research demonstrated how stress-related migraine pain originates from a certain molecule, begins in the dura and innervates throughout the dura and TG neurons. This current study and novel imaging technique further reveals potential connections between the TMJ, migraines and other headaches.
Potential of CGRP treatment
Calcitonin gene-related peptides (CGRP), molecules involved in transmitting pain signals and regulating inflammation, are often found in higher amounts in synovial fluid of TMJ disorder patients. Synovial fluid surrounds joints in the body, helping to reduce friction between bones and cartilage. Higher amounts of CGRP are often associated with increased pain and inflammation. Kim hypothesised in this study that a reduction in CGRP may reduce TMJ disorder symptoms. He found that CGRP antagonist added to the synovial fluid relieved both TMJ pain and hypersensitivity of TG neurons.
Currently, there are no Federal Drug Administration-approved medications for TMJ disorders other than non-steroidal anti-inflammatory drugs (NSAIDS). While some CGRP antagonist medications are FDA-approved for treating migraines, this study suggests these drugs may also provide relief for TMJ disorders. Confirmation of the positive effect of the drug on TMJ pain is a major leap forward in understanding how CGRP affect TMJ pain, said Kim.
“This imaging technique and tool allows us to see pain at its source – down to the activity of individual neurons – offering unprecedented insights into how pain develops and spreads. Our hope is that this approach will not only advance treatments for TMJ disorders but also pave the way for understanding and managing various chronic pain conditions more effectively,” said Kim.
Researchers at WashU Medicine and Stanford University developed a compound that relieves pain in mice but doesn’t affect the brain, thereby avoiding mind-altering side effects and abuse potential. The custom-designed molecule, derived from cannabis, may provide an alternative to opioids for treating chronic pain. The compound is illustrated here in cyan, nestled within a protein (green and purple) involved in sensing pain. Credit: Tasnia Tarana
In the quest to develop a safe, effective alternative to opioids, researchers have developed a compound that mimics a natural molecule found in the cannabis plant, harnessing its pain-relieving properties without causing addiction or mind-altering side effects in mice.
While more studies are needed, the compound shows promise as a nonaddictive pain reliever. The study, from Washington University School of Medicine in St. Louis and Stanford University, appears in Nature.
“There is an urgent need to develop nonaddictive treatments for chronic pain, and that’s been a major focus of my lab for the past 15 years,” said the study’s senior author Susruta Majumdar, PhD, a professor of anaesthesiology at WashU Medicine. “The custom-designed compound we created attaches to pain-reducing receptors in the body but by design, it can’t reach the brain. This means the compound avoids psychoactive side effects such as mood changes and isn’t addictive because it doesn’t act on the brain’s reward centre.”
Opioids dull the sensation of pain in the brain and hijack the brain’s reward system, triggering the release of dopamine and feelings of pleasure, which make the drugs so addictive. Despite widespread public health warnings and media attention focused on the dangers of opioid addiction, numerous overdose deaths still occur. In 2022, some 82 000 deaths in the U.S. were linked to opioids.
“For millennia, people have turned to marijuana as a treatment for pain,” explained co-corresponding author Robert W. Gereau, PhD, professor of anaesthesiology and director of the WashU Medicine Pain Center. “Clinical trials also have evaluated whether cannabis provides long-term pain relief. But inevitably the psychoactive side effects of cannabis have been problematic, preventing cannabis from being considered as a viable treatment option for pain. However, we were able to overcome that issue.”
The mind-altering properties of marijuana stem from natural molecules found in the cannabis plant referred to as cannabinoid molecules. They bind to a receptor, called cannabinoid receptor one (CB1), on the surface of brain cells and on pain-sensing nerve cells throughout the body.
Working with collaborators at Stanford University, co-first author Vipin Rangari, PhD, a WashU Medicine postdoctoral research associate in Majumdar’s laboratory, designed a cannabinoid molecule with a positive charge, preventing it from crossing the blood-brain barrier into the brain while allowing the molecule to engage CB1 receptors elsewhere in the body. By modifying the molecule such that it only binds to pain-sensing nerve cells outside of the brain, the researchers achieved pain relief without mind-altering side effects.
They tested the modified synthetic cannabinoid compound in mouse models of nerve-injury pain and migraine headaches, measuring hypersensitivity to touch as a proxy for pain. Applying a normally non-painful stimulus allows researchers to indirectly assess pain in mice. In both mouse models, injections of the modified compound eliminated touch hypersensitivity.
For many pain relievers, particularly opioids, tolerance to the medications over time can limit their long-term effectiveness and require higher doses of medication to achieve the same level of pain relief. In this study, the modified compound offered prolonged pain relief – the animals showed no signs of developing tolerance despite twice-daily treatments with the compound over the course of nine days. This is a promising sign that the molecule could be used as a nonaddictive drug for relief of chronic pain, which requires continued treatment over time.
Eliminating the compound’s tolerance resulted from the bespoke design of the compound. The Stanford collaborators performed sophisticated computational modeling that revealed a hidden pocket on the CB1 receptor that could serve as an additional binding site. The hidden pocket, confirmed by structural models, leads to reduced cellular activity related to developing tolerance compared to the conventional binding site, but it had been considered inaccessible to cannabinoids. The researchers found that the pocket opens for short periods of time, allowing the modified cannabinoid compound to bind, thus minimizing tolerance.
Designing molecules that relieve pain with minimal side effects is challenging to accomplish, said Majumdar. The researchers plan to further develop the compound into an oral drug that could be evaluated in clinical trials.
People who take over-the-counter pain relievers after a concussion may recover faster than those who do not take pain relievers, according to a preliminary study that will be presented at the American Academy of Neurology’s 77th Annual Meeting taking place April 5–9, 2025.
The study does not prove that pain relievers improve recovery after concussion; it only shows an association.
“These results are exciting as there are limited treatment options for concussion, and over-the-counter pain relievers are readily available and inexpensive,” said study author Kyle Arnold, MD, of the University of Washington in Seattle and a member of the American Academy of Neurology.
“If these results can be confirmed by a controlled study, they could guide us to possible treatment options for people after a concussion.”
The cohort study was conducted by the NCAA and US Department of Defense CARE Consortium and looked at NCAA athletes and military cadets who had concussions. A total of 813 people took over-the-counter pain relievers such as acetaminophen or ibuprofen and other non-steroidal anti-inflammatory drugs after their concussion and 848 people did not take any pain relievers.
Researchers looked at the amount of time it took the athletes to be cleared to return to activities with no restrictions at both 50% recovery and 90% recovery, meaning when 50% of the athletes in the study recovered and then later when 90% recovered.
People who took the pain relievers were 20% more likely to have a faster time before they were cleared to return to activities with no restrictions than those who did not take pain relievers. Those who took the medications were cleared at 50% recovery an average of two days faster, and at 90% recovery an average of seven days faster than those who took no medication.
People who took pain relievers were also about 15% more likely to return to having no symptoms more quickly than those who did not take pain relievers. At 50% recovery, those taking the medications had no symptoms one day sooner than those not taking the medications. At 90% recovery, they had no symptoms three days sooner.
Those who took pain relievers also had lower scores on tests of how severe their symptoms were overall and how severe their headaches were. The researchers also found that the earlier people took the pain relievers after the injury, the faster they recovered. For instance, at 50% recovery, those who started using pain relievers on the first day of their injury returned to play and had resolution of symptoms approximately eight days faster than those who started taking them after five or more days.
There was no difference between the type of pain reliever taken and how quickly people recovered.
“Early medication use appeared to be linked to shorter recovery times, but these findings require further validation through controlled trials,” Arnold said. “In the meantime, these preliminary results may help inform potential treatment options for people recovering from concussions, but additional studies are needed to provide more definitive recommendations.”
Chronic pain is complex and difficult to treat. Prescribing opioid pain medications has become controversial but may help some patients.
With the goal of informing clinician practice, a new study explores the harms and benefits of continuing and of discontinuing the long-term prescription of opioid medicines to adults with chronic pain. The authors analysed the opinions of 28 experts on the harms versus benefits of maintaining, tapering or terminating opioid pain medication prescriptions for chronic pain, a common condition worldwide that is typically quite difficult to treat.
The study authors found a lack of consensus among the experts on how to treat chronic (lasting three or more months) non-cancer pain. Slightly more than a third of the experts (36%) believed that long-term opioid therapy is beneficial, while an equal percentage indicated that it should be discontinued.
More than half of the experts believed that patients can experience harm from overly rapid tapering and discontinuation, while some recommended attempting a slow taper (even with a prior unsuccessful taper), possibly with addition of medications to manage withdrawal) in order not to maintain opioid therapy.
Some of the experts advocated for switching patients to buprenorphine, which diminishes the effects of physical dependency to opioids, such as withdrawal symptoms and cravings, and is used to treat pain. Some considered adding non-opioid pain therapies (including re-trying these therapies even if they were unhelpful in the past) as well as engaging in shared decision-making with the patient, although there was little consensus on how to accomplish these options.
Some, but not all of the experts, noted the benefit of addressing co-occurring conditions related to patient safety, such as alcohol use, mental health symptoms and opioid side effects.
Few of the experts brought up assessing or addressing opioid use disorder or overdose risk.
“The potential harms of opioid pain medication are well known, nevertheless patients can become habituated to them and want their physicians to continue prescribing them. Taking patients off opiates may result in return or worsening of chronic pain, mental health issues, drug seeking and potentially overdose and death. Additionally, these drugs could be used by someone else, possibly winding up on the street,” said study co-author Kurt Kroenke, MD of the Regenstrief Institute and the Indiana University School of Medicine. “On the benefit side, these drugs may be helping relieve the patient’s often debilitating pain which can impact the ability to interact with family, to hold a job, participate in social activities and many other aspects of life.”
A substantial number of people who are prescribed opioid pain medications continue to experience chronic pain. Dr Kroenke notes that these individuals may be good candidates for tapering to a lower dose, prescription discontinuation and moving on to effective, safer treatments for pain.
The authors conclude their analysis of the experts’ opinions, “Guidelines on whether to continue or taper opioids prescribed long- term may be difficult to utilize given professional liability concerns, changing regulations and health system initiatives, differing provider-patient perspectives on long-term opioid benefits and harms, and some providers’ beliefs that opioid dependence interferes with patients’ objectivity. In the meantime, individual care decisions that involve weighing relative harms should draw on longstanding norms of ethical medical care that call for informed consent and patient-provider conversations grounded in mutual respect.”
The study is published in the peer-reviewed journal Pain Practice.
The combination of prescribed central nervous system stimulants, such as drugs that relieve ADHD symptoms, with prescribed opioid medications is associated with a pattern of escalating opioid intake, a new study has found.
The analysis of health insurance claims data from almost 3 million US patients investigated prescribed stimulants’ impact on prescription opioid use over 10 years, looking for origins of the so-called “twin epidemic” of combining the two classes of drugs, which can increase the risk for overdose deaths.
“Combining the two drugs is associated with an increase in overdose deaths. This is something we know. But we didn’t know whether stimulant use has a causal role in high use of opioids, so we conducted a big data analysis of how these two patterns interacted over a long period of time,” said senior study author Ping Zhang, associate professor of computer science and engineering and biomedical informatics at The Ohio State University.
“What we found is that if someone is taking a stimulant and an opioid at the same time, they’re generally taking a high dose of the opioid,” he said. “And if the patient in this study population takes the stimulant before beginning opioid use, they are more likely to have higher doses of subsequent opioids.”
The research team obtained data on 22 million patients with 96 million opioid prescriptions from a large US health insurance database. Researchers established a cohort for this study of 2.9 million patients with an average age of 44 who had at least two independent opioid prescriptions between 2012 and 2021.
Because these prescriptions included a range of oral formulas – codeine, hydrocodone, methadone, oxycodone, morphine and others – researchers standardised every prescription to morphine milligram equivalents (MME) and calculated each patient’s monthly intake of opioids.
First author Seungyeon Lee, a PhD student in Zhang’s lab, used statistical modelling and classified patients into five baseline groups of opioid dosage trajectory over the 10-year study period: very low-dose, low-dose decreasing, low-dose increasing, moderate-dose increasing and high-dose sustained use.
“Some patients had stable low-dose opioid use, while others had increasing or high dose patterns over time,” Lee said.
Of the total cohort, 160 243 patients (5.5%) also were prescribed stimulants. The addition of a monthly calculated cumulative number of stimulant prescriptions to the model and statistical analysis showed a shift in the trajectory groups. Characteristics that could serve as risk factors for increasing opioid use also emerged in the data, Lee said.
Moderate-dose increasing and high-dose groups had an overall higher average MME and a higher proportion of patients with diagnoses of depression, anxiety and attention-deficit/hyperactivity disorder compared to other groups. The low-dose increasing group also had a higher proportion of patients with ADHD compared to the low-dose decreasing group.
The most common diagnoses linked to co-prescription of stimulants and opioids were depression and ADHD or ADHD and chronic pain.
“This was an important finding, that many patients with ADHD and depression, also experiencing chronic pain, have an opioid prescription,” said Zhang. “This cohort represents a very realistic health care problem.”
Even taking those factors into account, the model showed that stimulant use was key to driving up the odds that patients who took both stimulants and opioids would belong to a group of people who increased their doses of opioids.
“Stimulant use before initiating opioids and stimulant co-prescription with opioids are both positively associated with escalating opioid doses compared to other factors,” Lee said.
Analysis of geographic and gender data also offered some clues to opioid use patterns in the United States. Patients in the South and West regions had higher total opioid intakes over the 10-year study period compared to the Northeast and North Central regions, with the highest frequency of opioid prescriptions in the South and higher MMEs per prescription in the West. Males also had higher average daily opioid intakes than females.
The results linking high opioid doses and stimulant use suggest stimulants may be a driving force behind the emergence of the twin epidemic and offer evidence that regulation of stimulant prescribing may be needed for patients already taking prescription opioids, the researchers said. In addition to the increased risk of overdose death, co-using prescription stimulants and opioids can increase the risk for cardiovascular events and mental health problems, previous research has shown.
The American Academy of Neurology (AAN) has developed a new systematic review to summarise for neurologists and other clinicians the evidence for epidural steroid injections and whether they reduce pain and disability for people with certain kinds of chronic back pain. The systematic review is published online in Neurology®.
It updates a 2007 assessment by the AAN. With an epidural steroid injection, a steroid or corticosteroid medication is injected into the epidural space with the aim of helping reduce certain kinds of back pain.
“Chronic back pain is common and can negatively impact a person’s quality of life, making it difficult to move, sleep and participate in daily activities,” said author Carmel Armon, MD, of Loma Linda University School of Medicine in California and a Fellow of the American Academy of Neurology. “In our review, studies show epidural steroid injections may have limited efficacy. They may modestly reduce pain in some situations for up to three months and reduce disability for some people for up to six months or more.”
For the review, researchers analysed all available studies over a 16-year period. A total of 90 studies were examined. The review focused on the use of epidural steroid injections to reduce pain for people with radiculopathy and spinal stenosis. Radiculopathy is a condition caused by a pinched nerve in your spine. Spinal stenosis is a condition where spinal cord or nerves have become compressed because the space around the spinal cord has become too small. For people with radiculopathy, the review says studies show epidural steroid injections may be effective at modestly reducing pain and disability for up to three months after the procedure.
When compared to people not receiving the treatment, 24% more people receiving the treatment reported reduced pain, and 16% more reported reduced disability for up to 3 months. The treatment may also reduce disability for up to six months or more, with 11% more of those treated reporting reduced disability. Most of the reviewed studies looked at people with radiculopathy in their lower backs, so it is unclear how effective the treatment is for those with radiculopathy in their necks. For people with spinal stenosis, studies show epidural steroid injections might modestly reduce disability for up to six months or more after the procedure.
When compared to people not receiving the treatment, 26% more people receiving the treatment reported reduced disability up to three months, and 12% more for up to six months or more. The treatment was not found to reduce pain for up to three months. All studies looked at people with stenosis in their lower backs, so researchers do not know how effective the treatment is for people with stenosis in their necks.
“Our review affirms the limited effectiveness of epidural steroid injections in the short term for some forms of chronic back pain,” said author Pushpa Narayanaswami, MD, of Beth Israel Deaconess Medical Center in Boston and a Fellow of the American Academy of Neurology. “We found no studies looking at whether repeated treatments are effective or examining the effect of treatment on daily living and returning to work. Future studies should address these gaps.”
