Tag: pain management

Electroacupuncture Tops Standard Care for Cancer Pain

Image by wei zhu from Pixabay

A study found that electroacupuncture was superior to both auricular acupuncture and standard care for skeletal muscle pain management in cancer survivors.

Electroacupuncture reduced pain by 1.9 points on the 0-10 scale of the Brief Pain Inventory (BPI), compared to standard care. Auricular acupuncture, which was developed by the US military, reduced pain by 1.6 points compared to standard care, and was associated with more adverse effects (AE). Standard care consisted of analgesics, physical therapy, and steroid injections.

“The magnitude of effect of electroacupuncture was clinically important and durable,” the authors wrote. “This finding is consistent with evidence from other large acupuncture trials for chronic pain in the general population. Electroacupuncture has been shown to influence endogenous opioid release, which provides a mechanistic basis for chronic pain management.”

“The present trial includes a large and diverse group of cancer survivors and provides evidence that electroacupuncture provides additional benefits beyond usual care, including not only reduction in pain severity, but also improvements in physical function and quality of life and reductions in analgesic use.”

The PEACE Study enrolled patients with a history of cancer who had experienced musculoskeletal pain for at least three months and at least 15 of the preceding 30 days, with a worst pain intensity within the past week of ≥ 4 (moderate or greater) on the BPI.

Patients were randomised 2:2:1 to receive either electroacupuncture, auricular acupuncture (which were both delivered by licensed, experienced practitioners) or standard care. 

In electroacupuncture procedure, needles were placed at four sites near the location of pain and four additional sites elsewhere on the body to address comorbid symptoms. The treatments consisted of 10 weekly 30-minute sessions.

The auricular acupuncture, also known as ‘battlefield acupuncture’ had a standardised procedure where a single needle was inserted into the cingulate gyrus of one ear. The patient then walked for one minute, and if pain remained ≥ 1 on the BPI, another needle was inserted into the other ear. The process was repeated for the four remaining ear acupuncture points.

Mean baseline BPI scores ranged from 5.0 to 5.6. At week 12, mean BPI score had declined by 0.48 in the standard care group, 2.39 in the electroacupuncture group (P < 0.001), and 2.03 in the auricular acupuncture group (P < 0.001). The 0.36 difference between the two acupuncture groups exceeded the prespecified noninferiority margin of 0.657 for auricular versus electroacupuncture.

Source: MedPage Today

Journal information: Mao JJ, et al “Effectiveness of electroacupuncture or auricular acupuncture vs usual care for chronic musculoskeletal pain among cancer survivors: the PEACE randomized clinical trial” JAMA Oncol 2021; DOI: 10.1001/jamaoncol.2021.0310.

Review Finds Antidepressants Are Ineffective for Low Back Pain

A systematic review of studies on antidepressants for low back pain has shown that they are no more effective than placebo, but still could have even more serious side effects. 

Explaining the study, lead author Michael Ferraro, doctoral candidate at University of New South Wales (UNSW) Medicine & Health and Neuroscience Research Australia (NeuRA), said:  “Antidepressants are commonly prescribed to treat the symptoms of low back pain. However, prescription rates for antidepressants to manage low back pain are increasing worldwide, despite unclear evidence to support their efficacy and safety and conflicting advice in clinical guidelines.”

Across 17 studies with over 2500 participants, the researchers looked at differences in outcomes for pain, safety, function and depressive symptoms between people taking antidepressants and placebos. 

“We found that treating low back pain with antidepressants failed to lead to reductions in what patients might consider important benefits for pain or function,” Mr Ferraro said.

“We also discovered that people taking antidepressants for low back pain are more likely to stop treatment and experience side effects and might even experience more serious side effects.
“If people are taking antidepressants for low back pain and have any concerns about their treatment, they should consult their medical physician for advice.”

These results bring into question no less than six international guidelines that recommend the use of antidepressants for low back pain. In particular, the US has a guideline for duloxetine, a serotonin and norepinephrine reuptake inhibitor, chronic low back pain treatment.
“We believe the US recommendation for duloxetine could be reconsidered in light of our findings,” he said. “Ongoing recommendations for the use of antidepressants to treat low back pain are concerning, particularly given the increased risk of side effects.”

The low quality of the studies in general limited their findings, but no clear benefits of using antidepressants for low back pain could be identified.
“It is difficult to estimate the true effects of such medicines being used to treat low back pain. The majority of the studies were considered to be at high risk of bias and interestingly, the studies which showed the most promise were industry-sponsored. We recommend future research focuses on other types of medicines that may provide benefit to adults with low back pain, as well as non-pharmacological treatments, such as physiotherapy and exercise,” said Mr Ferraro.

Source: News-Medical.Net

Journal information: Ferraro, M.C., et al. (2021) Efficacy, acceptability, and safety of antidepressants for low back pain: a systematic review and meta-analysis. Systematic Reviews. doi.org/10.1186/s13643-021-01599-4.

Relugolix Combination Therapy is Promising for Fibroid Symptom Relief

A pair of clinical trials showed that combination therapy with relugolix reduced heavy bleeding and pain from uterine fibroids without the risk of side effects from low oestrogen levels.

Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, currently approved for men with advanced prostate cancer.  Uterine fibroids are common in women, and a quarter of those who are affected by them experience symptoms such as heavy menstrual bleeding and pain.

Injectable long-acting GnRH agonists are effective treatments for uterine fibroids, but cause BMD loss and thus are not generally eligible for long term use.  
In the two trials done in North and South America, Africa, and Europe, 71% and 73% of patients, respectively, who received relugolix together with estradiol and norethindrone acetate had significantly lower blood loss, compared with 19% and 15% in the placebo group.
Similar bone mineral density (BMD) measures were seen in the placebo and relugolix combination therapy groups; but MD decreased among patients who received relugolix monotherapy.

“For the first time, we have an oral treatment that can effectively and safely improve the symptoms of uterine fibroids, particularly heavy menstrual bleeding,” Ayman Al-Hendy, MD, PhD, of the University of Chicago Medicine, stated in an interview. and added that relugolix may be a viable, long-term alternative to the current surgical treatments available for fibroids patients.

“The goal of this program from the beginning was to develop an effective and long-term treatment as a viable alternative to hysterectomy,” Dr Al-Hendy said. “Any patient with uterine fibroids would be a good candidate for this non-surgical treatment.”

Lauren Schiff, MD, associate professor of minimally invasive gynecologic surgery at the school of medicine at the University of North Carolina at Chapel Hill, said that relugolix seems to be a good option for non-surgical treatment of fibroids.

Dr Schiff, who was not involved with the study, said that understanding bone mineral density (BMD) is key for using relugolix past six months. “If the bone density safety measure is maintained for long-term use, then this would be really ideal medication,” she told MedPage Today.

The trial’s primary endpoint was less than 80 ml blood loss, and >50% reduction in total blood loss from trial start. The investigators assessed several secondary outcomes, including amenorrhea, volume of menstrual blood loss, distress, pain, anaemia, fibroid volume, and uterine volume.

Around 388 participants were randomised in the first trial, and 382 in the second.

Around three-quarters of patients who received relugolix combination therapy reached the primary endpoint, with the treatment effects appearing similar baseline characteristics.

Amenorrhea over the last 35 days of the trial occurred in 52% and 50% of participants who received relugolix combination therapy in each trial, respectively. Pain was also reduced in the treatment groups.

Patients who received the combination therapy also had improvements in pain, distress from bleeding and pelvic discomfort, anaemia, and experienced reduced uterine volume. However, significant shrinkage in fibroid volume was not observed.

The prevalence of side effects was similar in the relugolix combination therapy group and the placebo cohort, with hot flashes being the most commonly reported side effect in the trial.

Strict assessment criteria for patients meant generalisability was limited. Additionally, study duration was only six months. The researchers plan to release data from a 28-week extension study, as well as a 52-week randomised-withdrawal trial, and these may shed more light on safety and efficacy in the long term.

Source: MedPage Today

Journal information: Al-Hendy A, et al “Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy” N Engl Med 2021; DOI: 10.1056/NEJMoa2008283.

New Surgery Improves Prosthetic Use and Reduces Pain

A new type of surgery that links muscles together may improve the precision of prosthetic use and also relieve pain.

In typical amputations, the muscle pairs (such as triceps and biceps) that work together to control the joints are severed. However, an MIT team has discovered that reconnecting these muscles that are in an agonistic-antagonistic (‘push-pull’) relationship improves the sensory feedback and thus precision of the affected limb.

“When one muscle contracts, the other one doesn’t have its antagonist activity, so the brain gets confusing signals,” explained Srinivasan, a former member of the Biomechatronics group now working at MIT’s Koch Institute for Integrative Cancer Research. “Even with state-of-the-art prostheses, people are constantly visually following the prosthesis to try to calibrate their brains to where the device is moving.”

The 15 patients who received the AMI surgery were able to flex their prosthetic ankle joint with more precision than those without it, who were only able to fully extend or flex their joint.

“Through surgical and regenerative techniques that restore natural agonist-antagonist muscle movements, our study shows that persons with an AMI amputation experience a greater phantom joint range of motion, a reduced level of pain, and an increased fidelity of prosthetic limb controllability,” says Hugh Herr, a professor of media arts and sciences, head of the Biomechatronics group in the Media Lab, and the senior author of the paper.

The surgery also had a completely unexpected benefit: the reduction of pain in the amputated area, which can be from neuromas or phantom limb pain. Phantom limb pain can occur in 80% of amputess. Six of the 15 AMI patients reported zero pain. This may be significant as in the five centuries since phantom limb pain was first described, there has not been much advancement in the understanding of it.

“Our study wasn’t specifically designed to achieve this, but it was a sentiment our subjects expressed over and over again. They had a much greater sensation of what their foot actually felt like and how it was moving in space,” Srinivasan says. “It became increasingly apparent that restoring the muscles to their normal physiology had benefits not only for prosthetic control, but also for their day-to-day mental well-being.”

To treat patients who had received the traditional amputation surgery, the team is also working on using muscle grafts to create a ‘regenerative AMI’ procedure that restores the effect of agonist and antagonist muscles.

Source: Medical Xpress

Journal information: Shriya S. Srinivasan el al., “Neural interfacing architecture enables enhanced motor control and residual limb functionality postamputation,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2019555118

Opioid Deaths Drop when Cannabis Stores are Near

A new US study suggests that opioid-related mortality rates fall in counties where there are legal cannabis stores.

Cannabis was first legalised for medical use in the US in 1996; recreational legalisation began in 2012 with a number of states following suit. Previous research on the effect of legal access to cannabis on opioid overdose mortality had produced conflicting results, with a 2014 study showing a slow increase in deaths, but a subsequent study showing that it reversed over time.

Data on opioid mortality for adults 21 and over was drawn from 2014-2018 CDC data, and a website called Weedmaps for cannabis dispensary details in the 23 states plus the District of Columbia where cannabis dispensaries were allowed to operate as of 2017.

The number of cannabis dispensaries in a county was negatively related to log-transformed age-adjusted opioid mortality rate (β -0.17, 95% CI -0.23 to -0.11). An increase in the number of storefront dispensaries from one to two was linked to a 17% reduction in death rates of all opioid types, and an increase from two to three stores was associated with a further 8.5% drop in mortality.

Eight states plus the District of Columbia allowed recreational storefronts and 15 allowed only medical dispensaries. An increase in medical dispensaries from one to two resulted in a 15% drop in mortality rate; an increase in recreational dispensaries from one to two led to an 11% drop.

Co-author Balázs Kovács, PhD, of Yale University School of Management, said: “We find this relationship holds for both medical dispensaries, which serve only patients who have a state-approved medical card or doctor’s recommendation, as well as for recreational dispensaries, which sell to adults 21 years and older.”

An accompanying editorial pointed out that the relationship was not clear, noting that were was no evidence of substitution. Additionally, individual experiences of benefits and harms could not be inferred.

Although findings are suggestive of a possible link between the increased prevalence of cannabis dispensaries and reduced opioid-related mortality, they do not show causality, Kovács emphasised. “While we find a particularly strong association between the prevalence of storefront dispensaries and fentanyl-related opioid deaths, it is not clear whether cannabis use and fentanyl mortality rates are more specifically linked, or if the strength of the association is due to the rise in fentanyl use and mortality rates during the study period,” he said. 
He added that the potential harms of cannabis, including cognitive development of adolescents, schizophrenia and other medical conditions, and public safety risks, should not be ignored.
Source:MedPage TodayJournal information:  Hsu G and Kovács B “Association between county level cannabis dispensary counts and opioid related mortality rates in the United States: panel data study” BMJ 2021; DOI: 10.1136/bmj.m4957.

New Study Challenges the Need for Some Post-surgical Opioids

Doctors must carefully weigh the pain relief value of opioids for patients against their potential for misuse and inducing opioid addiction even in patients with no history of substance abuse. Now, a new study challenges current practice by showing the effectiveness of an approach that takes a middle way to giving opioids.

Some 16 million people around the world suffer from opioid use disorder, which can result from opioid administration from surgery and for chronic pain. Opioids are highly addictive, with tolerance reached in days and addiction can occur within a matter of weeks, so there is every incentive to minimise exposure of patients to these effective but potentially dangerous medications.

To investigate the effectiveness of minimising opioid use, a team from Michigan Medicine at the University of Michigan conducted a study with 620 patients who had surgery in hospitals across Michigan, had their anaesthetic usage tracked, and filled in surveys within one to three months following their surgeries. The patients were split equally into two groups.
The first group received pre-surgery counseling emphasising non-opioid pain treatment as their first option. Some patients in this group received small, “just in case” prescriptions, but a third of them didn’t receive any opioid prescription at all after surgery.

The patients in the other group received standard care, that is, receiving the usual amount of opioids prescribed after such operations. The prescriptions received in fact were larger than in the opioid sparing group. Most patients didn’t take all of the pills, which if left lying around could be used inappropriately.

Patients in the two groups had the same surgery: either gallbladder removal, full or partial thyroid removal or hernia repair. However, both groups reported equal levels of quality of life and satisfaction with care when followed-up. Most surprisingly, the opioid-sparing group reported less pain overall.

First author Maia Anderson, MD, a resident in the U-M Department of Surgery, said: “It’s so exciting to think about the potential for opioid sparing postoperative pathways to not only reduce the risk of opioids for our patients, but also to substantially decrease the risk of opioid diversion into our communities.”

Senior author Ryan Howard, MD, Surgical Resident, Michigan Medicine commented: “We know that opioids pose serious risks to patients after surgery. We can protect patients from those risks by reducing or eliminating opioids after surgery. But that idea always raises the concern that patients will have uncontrolled pain and feel miserable. This study suggests that’s not the case – patients who get small opioid prescriptions, or even no prescription, are just as satisfied with their recovery after surgery.”

Source: News-Medical.Net

Journal information: Anderson, M., et al. (2020) Patient-Reported Outcomes After Opioid-Sparing Surgery Compared With Standard of Care. JAMA Surgery. doi.org/10.1001/jamasurg.2020.5646.

Withdrawal Symptoms of Discontinuing Medical Cannabis

A new study on the long terms effects of having used medical cannabis show that over half of people who used it experience withdrawal symptoms between use. And about one in ten experienced worsening alterations in sleep, mood, mental state, energy and appetite over two years.

Patients who use cannabis usually turn to it because of the failure of other pain medications, or to avoid the long-term risks of opioid use. However, the perception that it is “harmless” is incorrect, as it has cannabinoids that act on receptors in the brain, and from which the brain can experience withdrawal symptoms. This can even lead to cannabis use disorder.

Addiction psychologist Lara Coughlin, PhD, who led the analysis said, “Some people report experiencing significant benefits from medical cannabis, but our findings suggest a real need to increase awareness about the signs of withdrawal symptoms developing to decrease the potential downsides of cannabis use, especially among those who experience severe or worsening symptoms over time.”

After they had gone a significant time without cannabis, the 527 participants in the study were asked whether they had any one of 15 symptoms, ranging from irritability to nausea. Using an analytic method, they empirically grouped them into three groups ranging from mild or moderate symptoms to severe, with most of the symptoms. They then surveyed the patients again after one year and then again after two years. Those in the mild class showed the most stability in symptoms over time.

Younger participants were more likely to be in the severe group, and were more likely to have a worsening trajectory. Coughlin concluded that patients seeking cannabis use for pain need to discuss it with their health care providers, and seek psychosocial treatments such as cognitive behavioural therapy.

Source: Medical Express

Journal information: Coughlin, LN et al. Progression of cannabis withdrawal symptoms in people using medical cannabis for chronic pain. Addiction. 2021. DOI: 10.1111/add.15370

Opioid Use Linked to Pancreatic Cancer Risk

New research has shown that the use and misuse of the highly addictive opioid class of medications may pose an additional threat – pancreatic cancer

In the United States, opioid misuse has spiralled into one of the biggest healthcare epidemics facing the country. Of 70 000 deaths from substance abuse in the country in 2017, 68% involved opioids. Among patients prescribed opioids for chronic pain, 29% are misusing them and 12% have developed an opioid misuse disorder. Rates of pancreatic cancer are also on the increase in the US. In West Central Asia, opium use recently been linked to pancreatic cancer.Using Centres for Disease Control (CDC) data, the study’s researchers controlled for confounding variables, took opioid death rates as a surrogate for proscription and misuse, and compared it to incidences of pancreatic cancer. 

Analysing the dataset, they found that opioid use was associated with pancreatic cancer rates, with the opioid use rates predicting the pancreatic cancer trends years later.Faraz Bishehsari, MD, Ph.D., the corresponding author of the study, said: “Our mechanistic studies could provide further insights on the pathways that opioid could potentially impact progression of cancer.”

In order to confirm the findings, there is a need for sizeable population-based studies or longitudinal datasets that reliably track long-term outcomes in opioid users. Once these findings are confirmed by population-based studies, these will have an impact in considering alternative pain management methods in patients.Adding credence to this link is a recent post-hoc analysis of advanced cancer patients that showed patients receiving regular opioid antagonists had a significantly improved survival rate over placebo.

Source: Medical Xpress

Journal information: Usman Barlass et al. Opioid use as a potential risk factor for pancreatic cancer in the United States: An analysis of state and national level databases, PLOS ONE (2021). DOI: 10.1371/journal.pone.0244285

New Drug Relieves Rheumatoid Arthritis Pain

A new drug, otilimab, has shown effectiveness in treating rheumatoid arthritis (RA). Otilimab is a human monoclonal antibody which inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a large driver of immune-mediated inflammatory conditions.

The drug is currently being tested on its ability to suppress inflammation, tissue damage and pain in RA sufferers.

A multicentre, dose-ranging trial conducted with the drug. Participants were administered subcutaneous injections with one of five different dosages of otilimab (22.5 mg, 45 mg, 90 mg, 135 mg, or 180 mg) or placebo weekly for five weeks. Thereafter, they received injections once every two weeks for one year. The results showed a rapid reduction in tenderness and swelling, and a very high reduction in pain.

The study was unusual in that it offered an escape arm. It is often difficult to recruit participants when they know they may be receiving a dummy injection, and so if, after 12 weeks the participants  on the placebo arm derived no benefit, they were transferred to the highest dose arm of 180mg.

Source: Medical Xpress

Journal information: Christopher D Buckley et al, Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study, The Lancet Rheumatology (2020). DOI: 10.1016/S2665-9913(20)30229-0

Anaesthetic Clues Hidden in Tarantula Venom

In a finding that promises new research into pain management, a tarantula toxin molecule has been revealed to use a “stinger” to permanently close the voltage sensors on nerve cells’ sodium channels.

Chronic pain is difficult to treat, and attempts to seek relief can sometimes lead to opiate overdose, addiction, prolonged withdrawal, and even death. This means that there is a critical need to develop pain management medications that are safer, more effective and non-addictive. Tarantula toxin is of interest because it has to be fast-acting, shutting down the nerves of the tarantula’s prey and immobilising it before it can escape.

The tarantula toxin’s mechanism of action has proved elusive: the tarantula toxin-ion channel chemical complex has been hard to capture in its functional form. This has made it especially challenging to replicate the calcium-channel blocking effect in a small molecular form suitable for anaesthetic compounds. To overcome this obstacle, the researchers took a toxin-binding region from a specific type of human sodium channel that is key to pain transmission and imported it into their bacterium-derived model ancestral sodium channel. In doing so, they successfully obtained a clear molecular view of the configuration of the potent toxin from tarantula venom as it tightly binds to the sodium channel receptor site.

Prof William Catterall of the University of Washington School of Medicine explains: “Remarkably, the toxin plunges a ‘stinger’ lysine residue into a cluster of negative charges in the voltage sensor to lock it in place and prevent its function. Related toxins from a wide range of spiders and other arthropod species use this molecular mechanism to immobilise and kill their prey.”

The researchers hope that these insights will lead to the development of a new variety of anaesthetic compounds.

Source: News-Medical.Net