Acute low back pain is a common cause of disability, and while opioid drugs are effective at controlling pain, excessive use creates a great potential for substance abuse. An analysis in the Journal of Orthopaedic Research examined which non-opioid drugs are best for relieving this pain.
The analysis, which included all randomised controlled trials published to date (18 studies with 3478 patients), showed that muscle relaxants and non-steroidal anti-inflammatory drugs (NSAIDs) could effectively and rapidly reduce symptoms.
The combination of NSAIDs and paracetamol was associated with a greater improvement than NSAIDs alone.
“This is a first step towards the optimisation of the management of acute low back pain. However, specific patient characteristics such as having allergies and comorbidities must always be taken into consideration,” said lead author Alice Baroncini, MD, PhD, of RWTH University Hospital in Germany. “Further research will need to focus on the identification of the type of drugs that not only offer the best and quickest pain relief, but also show the lowest rate of symptom recurrence.”
Awareness during anaesthesia is an extremely rare but horrific risk for patients. Now, for the first time, neuroscientists have identified brain structures which could predict an individual’s predisposition this phenomenon. The findings, just published in the journal Human Brain Mapping,could help identify patients who need larger anaesthetic doses.
Although anaesthesia has been used in clinical medicine for over 150 years, scientists do not fully understand why its effect on people is so varied. One in four patients presumed to be unconscious during general anaesthesia may in fact have subjective experiences, such as dreaming. Estimated to occur in 1:1000 to 1:20 000 cases, some patients may have awareness under general anaesthetic. These experiences may range from hearing sounds to the pain of surgery combined with the sensation of suffocation and paralysis in the setting of neuromuscular blockade.
The researchers from Trinity College Dublin found that one in three participants were unaffected by moderate propofol sedation in their response times, thus thwarting a key aim of anaesthesia – the suppression of behavioural responsiveness.
The research also showed, for the first time, that the participants who were resistant to anaesthesia had fundamental differences in the function and structures of the fronto-parietal regions of the brain to those who remained fully unconscious. Crucially, these brain differences could be predicted prior to sedation.
Lorina Naci, Associate Professor of Psychology, Trinity who lead the research said:
“The detection of a person’s responsiveness to anaesthesia prior to sedation has important implications for patient safety and wellbeing. Our results highlight new markers for improving the monitoring of awareness during clinical anaesthesia. Although rare, accidental awareness during an operation can be very traumatic and lead to negative long-term health outcomes, such as post-traumatic stress disorder, as well as clinical depression or phobias.”
“Our results suggest that individuals with larger grey matter volume in the frontal regions and stronger functional connectivity within fronto-parietal brain networks, may require higher doses of propofol to become nonresponsive compared to individuals with weaker connectivity and smaller grey matter volume in these regions.”
The research, conducted in Ireland and Canada, investigated 17 healthy individuals who were sedated with propofol, the most common clinical anaesthetic agent. The participants’ response time to detect a simple sound was measured when they were awake and as they became sedated. Brain activity of 25 participants as they listened to a simple story in both states was also measured.
People with cluster headaches may be more than three times more likely to have other medical conditions such as heart disease, mental disorders and other neurologic diseases, according to a study published in Neurology.
Cluster headaches are short but extremely painful headaches that can occur many days, or even weeks, in a row. The headaches can last anywhere from 15 minutes to three hours.
“Around the world, headaches have an incredibly negative impact on people’s quality of life, both economically and socially,” said study author Caroline Ran, PhD, of the Karolinska Institutet in Stockholm, Sweden. “Our results show that people with cluster headaches not only have an increased risk of other illnesses, those with at least one additional illness missed four times as many days of work due to sickness and disability than those with just cluster headaches. They also have a higher chance of a long-term absence from work.”
The study involved 3240 people with cluster headaches ages 16–64 in Sweden who were compared to 16 200 matched controls. The majority were men, typical of cluster headache.
Researchers looked at work records and disability benefits to determine how many days during a year people were absent from work due to sickness and disability.
Among those with cluster headaches, 92%, or 2977 people, had at least one additional illness. Of those without cluster headaches, 78%, or 12 575 people, had two or more illnesses.
Of those with cluster headaches, more women had additional illnesses than men, 96% and 90% respectively.
The average number of days a person was absent due to sickness and disability was nearly twice as high among people with cluster headaches with 63 days compared to those without cluster headaches with 34 days.
People with cluster headaches and at least one additional illness had four times as many absence days compared to people with cluster headaches who did not have an additional illness.
“Increasing our understanding of the other conditions that affect people with cluster headache and how they impact their ability to work is very important,” added Ran. “This information can help us as we make decisions on treatments, prevention and prognoses.”
A limitation of the study was that information on personal data, such as smoking, alcohol consumption and BMI, which could affect the occurrence of diseases, was not available.
A comparison of spinal cord stimulators (SCS) revealed that the implants only offer a notable benefit within the first year of use, while also being associated with a high risk of adverse effects – nearly one in five, and a similar number requiring device revision or removal.
In this propensity-matched comparative effectiveness research analysis of 7560 insured individuals published in JAMA Neurology, treatment with SCS was not associated with a reduction in use of opioids, pain injections, radiofrequency ablation, or spine surgery at two years.
The study used administrative claims data, including longitudinal medical and pharmacy claims, from 2020–2021. Patients with incident diagnosis codes for failed back surgery syndrome, complex regional pain syndrome, chronic pain syndrome, and other chronic postsurgical back and extremity pain were included in this study.
Patients were an average age of 63.5 years and 59.3% were female. Among matched patients, during the first year, patients treated with SCSs had higher odds of chronic opioid use (adjusted odds ratio [aOR], 1.14) compared with patients treated with CMM but lower odds of epidural and facet corticosteroid injections (aOR, 0.44), radiofrequency ablation (aOR, 0.57), and spine surgery (aOR, 0.72).
During the second year, these beneficial effects disappeared. Compared to CMM there were no significant differences with SCS use in:
chronic opioid use (aOR, 1.06),
epidural and facet corticosteroid injections (aOR, 1.00)
radiofrequency ablation (aOR, 0.84)
spine surgery (aOR, 0.91)
Overall, 226 of 1260 patients (17.9%) treated with SCS experienced SCS-related complications within 2 years, and 279 of 1260 patients (22.1%) had device revisions and/or removals, which were not always for complications. Total costs of care in the first year were $39 000 higher with SCS than CMM and similar between SCS and CMM in the second year.
In an accompanying editorial, Prasad Shirvalkar, MD, PhD, and Lawrence Poree. MD, PhD, MPH conclude: “The findings appear to belie the popular belief that SCS may result in reduced opioid medication usage or overall fewer physician visits in the years immediately following device implant.”
They continue: “Notably, a formal cost-utility analysis was not done, and therefore caution is advised not to interpret these results as an argument against the therapeutic effectiveness of SCS for reducing symptoms or improving daily function. After all, there is surely some intrinsic social value to alleviating symptoms and improving individual function that may justify health care costs for chronic pain, just as in the practical treatment of cancer or heart disease.”
In many trials testing cannabis for pain relief, there is no significant difference between placebo and the active cannabinoid substance. Still, these studies receive significant media coverage regardless of the clinical outcome, according to a study published in JAMA Network Open.
“We see that cannabis studies are often described in positive terms in the media regardless of their results,” says the study’s first author Filip Gedin, postdoc researcher at Karolinska Institutet. “This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”
The study is based on an analysis of published clinical studies in which cannabis has been compared with placebo for the treatment of clinical pain. The change in pain intensity before and after treatment were the study’s primary outcome measurement.
The analysis drew on 20 studies published up to September 2021 involving almost 1500 individuals.
No difference between cannabis and placebo
The results of the study show that pain is rated as being significantly less intense after treatment with placebo, with a moderate to large effect. The researchers also observed no difference in pain reduction between cannabis and placebo, which corroborates results from another recently published meta-analysis.
“There is a distinct and clinically relevant placebo response in studies of cannabis for pain,” says Dr Gedin.
The researchers also examined a possible connection between the magnitude of the therapeutic effect shown by the cannabis studies and the coverage they receive in the media and in academic journals. Media presence was measured through Altmetric, which is a method of evaluating mentions in the media, in blogs and on social media. Academic impact was measured in terms of citations by other researchers.
The analysis of media presence included a total of 136 news items in traditional media and in blogs and was categorised as positive, negative or neutral, depending on how the results were presented concerning the effectiveness of cannabis as a treatment for pain.
Lots of media attention
The researchers found that the cannabis studies received much greater media attention than other published studies. The coverage was substantial regardless of the magnitude of the placebo response and regardless of the therapeutic effect of cannabis. They also observed no link between the proportion of positively described news about a study and the effect it reported.
The researchers add the caveat that their study combined trials of varying designs and quality and therefore the results should be interpreted with caution.
This research was financed by Riksbankens Jubileumsfond (Karin Jensen). The researchers report no potential conflicts of interest.
Some clinicians have recommended vitamin D supplements to ease the muscle aches of patients taking a statin, but a new study published in the journal JAMA Cardiology shows the vitamin appears to have no substantial impact.
While non-randomised studies have reported vitamin D to be an effective treatment for statin-associated muscle symptoms, the new study, which is the first randomised clinical trial to look at the effect of vitamin D on statin-associated muscle symptoms, was large enough to rule out any important benefits.
In the randomised, double-blind trial, 2083 participants took either 2000 units of vitamin D supplements daily or a placebo. The study found participants in both categories were equally likely to develop muscle symptoms and discontinue statin therapy.
Over 4.8 years of follow-up, statin-related muscle pain was reported by 31% of the participants assigned vitamin D and 31% assigned a placebo.
“We had high hopes that vitamin D would be effective because in our clinic and across the country, statin-associated muscle symptoms were a major reason why so many patients stopped taking their statin medication,” said senior author Dr Neil Stone, professor at Northwestern University. “So, it was very disappointing that vitamin D failed a rigorous test. Nevertheless, it’s important to avoid using ineffective treatments and instead focus on research that can provide an answer.”
Statins and vitamin D supplements are two of the most commonly used medications in American adults. About 30 to 35 million Americans are prescribed statins, and about half of the population aged 60 and older take a vitamin D supplement.
“We took advantage of a large placebo-controlled randomised trial to test whether vitamin D would reduce statin-associated muscle symptoms and help patients keep taking their statins,” said lead study author Dr Mark Hlatky, a professor of health policy and cardiovascular medicine at Stanford. “The placebo control in the study was important because if people think vitamin D is supposed to reduce their muscle pains, they just might feel better while taking it, even if vitamin D has no specific effect.”
Trial was a sub study within a larger clinical trial
The 2083 patients were among the larger cohort of participants in the VITamin D and Omega-3 Trial (VITAL), which randomised nearly 26 000 participants to double-blind vitamin D supplementation to determine whether it would prevent cardiovascular disease and cancer. This provided researchers a unique opportunity to test whether vitamin D reduces muscle symptoms among participants who initiated statins during the follow-up period of the larger VITAL trial. The mean age of the study participants was 67, and 51% were women.
“Randomised clinical trials are important because many very good ideas don’t work as well as we had hoped when they are put to the test,” Hlatky said. “Statistical associations do not prove a cause-and-effect relationship. Low levels of vitamin D are associated with many medical problems, but it turns out that giving people vitamin D does not generally fix those problems.”
For patients who report statin-associated muscle pains
Dr Stone noted that sometimes the secret for understanding patients who have difficulty with statins is analysing other medications they’re taking, determining whether or not they have associated metabolic or inflammatory conditions, counselling them on their ability to hydrate adequately and, importantly, discussing “pill anxiety.”
“For those who have difficulties with statins, a systematic appraisal by a physician with experience in dealing with these matters is still very important,” Stone said.
The US Centers for Disease Control have released new opioid prescribing guidelines that do not promote strict thresholds for dose and duration of pain medications. The new guidelines, which update and replace the controversial 2016 guidelines, are published in Morbidity and Mortality Weekly Report.
The previous guidelines had been interpreted as imposing strict opioid dose and duration limits and was misapplied by some organisations, leading to a clarification being released in 2019. Other organisations, such as the European Pain Federation, had stated that overly strict guidelines for their own countries were hampering effective pain management.
The 2022 recommendations are voluntary and give clinicians and patients flexibility to support individual care, said Christopher Jones, PharmD, DrPH, MPH, acting director of CDC’s National Center for Injury Prevention and Control in a press briefing. He stressed that they should not be used as a inflexible rule, or applied as a rigid standard of care, or replace clinical judgement on personalised treatment.
“Patients with pain should receive compassionate, safe, and effective pain care,” Jones stated. “We want clinicians and patients to have the information they need to weigh the benefits of different approaches to pain care, with the goal of helping people reduce their pain and improve their quality of life.”
The guidance covers four key areas: opioids initiation for pain, opioid and dosage selection, deciding prescription duration and conducting follow-up, and assessing risk and potential harms of opioids. It also suggests that clinicians work with patients to incorporate plans to mitigate risks, including offering naloxone.
The document indicates opioids should not be considered as first-line or routine therapy for subacute or chronic pain, and points out that, for many kinds of acute pain, non-opioid therapies are often better choices.
“For patients receiving opioids for 1 to 3 months (the timeframe for subacute pain), the 2022 guideline recommends that clinicians avoid continuing opioid treatment without carefully reassessing treatment goals, benefits, and risks in order to prevent unintentional initiation of long-term opioid therapy,” noted Deborah Dowell, MD, MPH and colleagues in a commentary published in the New England Journal of Medicine.
For chronic pain, clinicians should make maximal use of non-opioid therapies and consider initiating opioid therapy only if pain reduction benefits outweigh the risk, Dowell and colleagues noted. When needed, clinicians should initiate opioids at the minimum effective dose, assess risks and benefits before increasing dosage, and avoid raising dosage above levels likely to yield diminishing returns, they added.
The new guideline offers tips for tapering opioids when warranted, but is not intended to lead to rapid opioid tapering or discontinuation, Jones noted. The recommendations do not apply to sickle cell disease-related pain, cancer pain, and palliative or end-of-life care.
The 2022 document incorporated public feedback since the new version was first proposed in February, including patients discussing their experiences with pain or opioid addiction and barriers to pain care.
“The science on pain care has advanced over the past 6 years. During this time, CDC has also learned more from people living with pain, their caregivers, and their clinicians,” said Dowell in a statement. “We’ve been able to improve and expand our recommendations by incorporating new data with a better understanding of people’s lived experiences and the challenges they face when managing pain and pain care.”
A new study using a mouse model suggests that a short-term exposure to a high-fat diet may be linked to pain sensations, such as from a light touch, even without a prior injury or a pre-existing condition like obesity or diabetes. This finding may help in part explain the severity of the opioid crisis.
The study, published in Scientific Reports, compared the effects of eight weeks of different diets on two cohorts of mice. One group received normal chow, while the other was fed a high-fat diet in a way that did not precipitate the development of obesity or high blood sugar, both of which are conditions that can result in diabetic neuropathy and other types of pain.
The researchers found that the high-fat diet induced hyperalgesic priming – a neurological change that represents the transition from acute to chronic pain – and allodynia, which is pain resulting from stimuli that do not normally provoke pain.
“This study indicates you don’t need obesity to trigger pain; you don’t need diabetes; you don’t need a pathology or injury at all,” said Dr Michael Burton, assistant professor of neuroscience and corresponding author of the article. “Eating a high-fat diet for a short period of time is enough – a diet similar to what almost all of us in the US eat at some point.”
The study also compared obese, diabetic mice with those that just experienced dietary changes.
“It became clear, surprisingly, that you don’t need an underlying pathology or obesity. You just needed the diet,” Burton said. “This is the first study to demonstrate the influential role of a short exposure to a high-fat diet to allodynia or chronic pain.”
Diet itself caused markers of neuronal injury.
Western diets are rich in fats – in particular saturated fats, which have proved to be responsible for an epidemic of obesity, diabetes and associated conditions. Individuals who consume high amounts of saturated fats – like butter, cheese and red meat – have high amounts of free fatty acids circulating in their bloodstream that in turn induce systemic inflammation.
Recently, scientists have shown that these high-fat diets also increase existing mechanical pain sensitivity in the absence of obesity, and that they can also aggravate pre-existing conditions or imped injury recovery. To date, no studies have explained how high-fat diets alone can be a sensitising factor in inducing pain from nonpainful stimuli, such as a light touch on the skin, Burton said.
“We’ve seen in the past that, in models of diabetes or obesity, only a subsection of the people or animals experience allodynia, and if they do, it varies across a spectrum, and it isn’t clear why,” Burton said. “We hypothesized that there had to be other precipitating factors.”
The researchers examined blood levels of fatty acids in the mice. They found that a fatty acid called palmitic acid, the most common saturated fatty acid in animals, binds to a particular receptor on nerve cells, a process that results in inflammation and mimics injury to the neurons.
“The metabolites from the diet are causing inflammation before we see pathology develop,” Burton said. “Diet itself caused markers of neuronal injury.
The mechanism behind this transition is important because it is the presence of chronic pain – from whatever source – that is fuelling the opioid epidemic
“Now that we see that it’s the sensory neurons that are affected, how is it happening? We discovered that if you take away the receptor that the palmitic acid binds to, you don’t see that sensitising effect on those neurons. That suggests there’s a way to block it pharmacologically.”
Burton said the next step will be to focus on the neurons themselves – how they are activated and how injuries to them can be reversed. It is part of a larger effort to understand better the transition from acute to chronic pain.
“The mechanism behind this transition is important because it is the presence of chronic pain – from whatever source – that is fuelling the opioid epidemic,” he said. “If we figure out a way to prevent that transition from acute to chronic, it could do a lot of good.”
Burton said he hopes his research encourages health care professionals to consider the role diet plays in influencing pain.
“The biggest reason we do research like this is because we want to understand our physiology completely,” he said. “Now, when a patient goes to a clinician, they treat a symptom, based off of an underlying disease or condition. Maybe we need to pay more attention to how the patient got there: Does the patient have diabetes-induced or obesity-induced inflammation; has a terrible diet sensitised them to pain more than they realized? That would be a paradigm shift.”
With few solutions available, treatment of knee osteoarthritis is challenging, but a randomised control trial published in Arthritis and Rheumatology has found that, at least for short-term relief, ultrasound-guided genicular nerve block (GNB) was effective.
The global prevalence of knee osteoarthritis (OA) is ~22.9% of over-40s. Knee OA is a significant cause disability and potentially loss of independence. Treatment remains challenging, with nonsurgical management options such as education, weight loss, exercise therapy, and walking aids. Few recommended pharmacotherapeutic options exist for knee OA, with surgical joint replacement being a definitive treatment strategy for patients with severe disease who are unresponsive to conservative care. For many patients, such as people who are frail or elderly or people with complex comorbidities, surgical intervention may not be suitable.
In a 12-week parallel-group, placebo-controlled randomised trial of GNB, patients in the active arm received 3 injections of 5.7 mg celestone chronodose (1ml) and 0.5% bupivacaine (3ml) to the inferomedial, superomedial, and superolateral genicular nerves. Patients in the placebo arm received saline injections. An experienced radiologist or rheumatologist with the assistance of a senior sonographer used ultrasound to locate the nerves.
At baseline and at weeks 2, 4, 8, and 12, patients recorded their pain and disability on self-report scales. Patients in the active group reported improvements in pain scores at 2, 4, 8, and 12 weeks with a diminution of the effect over time.
These results reflect comparator groups, which also reported an effect reduction at 12 weeks.
“This study demonstrates that genicular nerve block is an effective short-term therapy for pain management in people with knee osteoarthritis,” said corresponding author Ernst M. Shanahan, BMBS, MPH, MHPE, PhD, FAFOEM, FRACP, of Flinders University. “We think it may be a useful treatment option for this group of people, in particular those waiting for, or wishing to defer surgery.”
In a new study published in Molecular Biology of the Cell, a team of Rensselaer Polytechnic Institute researchers identified a previously unknown propofol anaesthetic mechanism, which, despite its frequent clinical application, is poorly understood.The study found that propofol exposure impacted the transportation of proteins to the surface of neurons, interrupting their function.
Almost all animal cells, including human cells, are highly compartmentalised and rely on efficient movement of protein material between compartments in vesicles. This transport must be efficient and highly specific to maintain cellular organisation and function.
The research team was led by Dr Marvin Bentley, associate professor at Rensselaer Polytechnic Institute, whose laboratory studies vesicle transport in neurons. Neurons are particularly reliant on vesicle transport because axons, often organised in nerve bundles. can span distances of up to 100cm in humans. Errors in vesicle transport have been linked to neurodevelopmental and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
This new study found that propofol affects a family of proteins called kinesins – small ‘motor proteins’ that move vesicles on tiny filaments called microtubules.
Dr Bentley’s team observed that vesicle movement of two prominent kinesins, Kinesin-1 and Kinesin-3, was substantially reduced in cells exposed to propofol. The team then showed that propofol-induced transport delays led to a significant drop in protein delivery to axons.
“The mechanism by which propofol works is not fully understood,” Bentley said. “What we discovered was unexpected: propofol altered the trafficking of vesicles in live neurons.”
Overall, the research contributes significantly to our understanding of how propofol works. Most studies on propofol’s anaesthetic mechanism have instead focused on its interaction with an ion channel called the GABAA receptor, which inhibits neurotransmission when activated.
This new study demonstrates that vesicle transport is an additional mechanism that may be important for propofol’s anaesthetic effect. Discovery of this new propofol effect has important applications for human health and may lead to the development of better anaesthetic drugs.
