Category: Pain Management

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Intraosseous Morphine Reduces Pain after Knee Replacement Surgery

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In knee replacement patients, injecting a combination of morphine and the antibiotic vancomycin into the tibia of their knee joint resulted in less pain post-surgery compared to those who received the infusion without morphine during surgery. The findings were published in The Journal of Arthroplasty.

“Despite many technological advances, controlling pain after total knee arthroplasty can be challenging; most patients experience considerable pain and discomfort, especially in the first couple of weeks into their recovery,” explained Kwan “Kevin” Park, MD, orthopaedic surgeon at Houston Methodist. “Intraosseous infusion, which involves injecting medication directly into the bone marrow, allows us to control pain pre-emptively so that patients don’t have to take as much pain medicine later on.”

Total knee replacement is the recommended treatment to alleviate chronic pain caused by damage to the knee joint from arthritis or injury.

Despite the high frequency and favourable outcomes of the surgical procedure, the manipulation of soft tissue and resurfacing damaged bones during knee replacement cause pain in the early postoperative periods.

“Twenty years ago, patients would remain in the hospital for several days after their surgery and receive extremely high-dose narcotics to help with their postoperative pain,” Dr Park said. “But there has been a paradigm shift; patients are often discharged the same day after knee replacement surgery, and we use multimodal pain management techniques that work much better for pain control and require fewer narcotics.”

These multimodal regimens, he added, often include a combination of medications, such as nonsteroidal anti-inflammatory drugs, opioids and neurogenic agents that act on the nervous system, administered both pre-emptively and after the surgery. However, opioid medications, although very effective in managing pain, have known side effects, like constipation and nausea, and some individuals are allergic to opiates. Opioid medication can be highly addictive, as well. Furthermore, a consensus on the optimal preoperative protocol to mitigate pain is lacking.

Previously, the researchers demonstrated that injecting the antibiotic vancomycin directly into the tibia before surgery helped in reducing infection by reaching a higher concentration of the drug in the knee. Motivated by this success, they investigated whether adding morphine into the tibial bone with a standard antibiotic solution could improve postoperative pain management.

For the study, the team included 48 patients needing total knee replacement surgery. Of these patients, half were randomised to receive vancomycin and morphine injected directly into the bone marrow, using an infusion device that was inserted into the tibial tubercle region, and the remainder were only administered vancomycin as controls. Post-surgery, the researchers monitored patient-reported pain, nausea and opioid use for up to 14 days after surgery. Serum levels of morphine and interleukin-6 were measured in all study participants for 10 hours after the operation.

Analysis showed that the vancomycin and morphine group had lower pain scores after their knee replacements compared to the controls. This was effective up to two weeks after surgery. Further, these patients also reported having less pain for several days even though they had similar interleukin-6 inflammatory marker levels as the control group. Taken together, although the patients who received pain medication infused directly into the tibia during surgery had comparable inflammation, these patients were taking less pain medication post-surgery.

Dr Park noted that this infusion of opiates directly into the bone marrow during surgery could potentially even facilitate a swifter recovery of the knee joint.

“By infusing pain medication intraosseously we’re able to reduce postoperative pain for up to two weeks, reduce the number of pain pills patients need and even possibly improve the function of the knee over time,” he said. “Our technique also can improve the multimodal pain management protocol we have been using for knee replacement over the years.” 

Source: Houston Methodist

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Clinical Trial Finds Dry Cupping Relieves Chronic Back Pain

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In the Journal of Acupuncture and Meridian Studies, researchers report that combining ear acupuncture with dry cupping to treat chronic back pain, and showed that it can provide effective relief over acupuncture alone.

Dating back to ancient times, cupping therapy is a technique that uses cups placed over the skin to create negative pressure through suction. In 400 BC, Herodotus listed wet and dry cupping as a treatment for many ailments, including maldigestion, lack of appetite, and headaches. Ear acupuncture, also known as ‘battlefield acupuncture’ has also been modernised by the US military as a simple treatment method in challenging environments.

The open-label, randomised, parallel-group controlled clinical trial recruited 198 adults with chronic back pain. The people were randomised to receive only ear acupuncture as the control group or receive ear acupuncture along with dry cupping as the experimental group.

Interventions were performed in five sessions, once a week, lasting five weeks. Evaluations were performed before the first session, after the last session, and seven days after the second evaluation, using the Brief Pain Inventory to assess the impact of pain on daily activities and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) to assess the quality of life.

Between the initial and final sessions, there were significant changes in daily activities , activity, work, mood, relationships, sleep, and in the physical, psychological and social relationships domains for both the control and experimental groups. Improved perception of quality of life and satisfaction with health were observed for the participants in the experimental group.

Source: Keck School of Medicine USC

Categories : New Compounds and Treatments Pain ManagementTags :

A Potent New Non-opioid Analgesic

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Researchers co-led by University of Warwick have discovered a potent new non-opioid analgesic with potentially fewer side effects compared to other potent painkillers.

Their study found that a compound called BnOCPA (benzyloxy-cyclopentyladenosine), is a potent and selective analgesic which is non-addictive. BnOCPA also has a unique mode of action and potentially opens a new pipeline for the development of new analgesic drugs.

The research is published in Nature Communications.

Chronic pain has a negative impact on quality of life and many commonly prescribed analgesics come with side effects. Opioid drugs, such as morphine and oxycodone, can lead to addiction and are dangerous in overdose.

Drugs that act on G protein-coupled receptors (GPCRs) are one possibility, but their development is hampered by the propensity of GPCRs to couple to multiple intracellular signalling pathways. A unique feature of BnOCPA is that it only activates one type of GPCR, leading to very selective effects and thus reducing potential side effects.

University of Warwick’s Dr Mark Wall, who led the research said: “The selectivity and potency of BnOCPA make it truly unique and we hope that with further research it will be possible to generate potent painkillers to help patients cope with chronic pain.”

Source: University of Warwick

Categories : Pain ManagementTags :

Mechanism Behind Sound and Pain Suppression Identified in Mice

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Sound is known to suppress the sensation of pain, and now scientists have identified the neural mechanisms through which sound blunts pain in mice. The findings, which could inform development of safer methods to treat pain in humans, were published in Science.

“We need more effective methods of managing acute and chronic pain, and that starts with gaining a better understanding of the basic neural processes that regulate pain,” said the director of the National Institute of Dental and Craniofacial Research (NIDCR), Rena D’Souza, DDS, PhD. “By uncovering the circuitry that mediates the pain-reducing effects of sound in mice, this study adds critical knowledge that could ultimately inform new approaches for pain therapy.”

Studies as far back as 1960, have shown that music and other kinds of sound can help alleviate acute and chronic pain in humans, including pain from dental and medical surgery, labour and delivery, and cancer. Yet the mechanism behind this remained elusive.

“Human brain imaging studies have implicated certain areas of the brain in music-induced analgesia, but these are only associations,” said co-senior author Yuanyuan (Kevin) Liu, PhD, at NIDCR. “In animals, we can more fully explore and manipulate the circuitry to identify the neural substrates involved.”

The researchers first exposed mice with inflamed paws to three types of sound: a pleasant piece of classical music, an unpleasant rearrangement of the same piece, and white noise. Surprisingly, all three types of sound, when played at a low intensity relative to background noise (about the level of a whisper) reduced pain sensitivity in the mice. Higher volume had no effect on their pain sensitivity.

Researchers discover how sound reduces pain in mice
Inhibition of auditory cortex inputs to the thalamus drives sound-induced analgesia. Credit: Conghuan Ye

“We were really surprised that the intensity of sound, and not the category or perceived pleasantness of sound would matter,” Dr Liu said.

To explore the brain circuitry underlying this effect, the researchers trace connections between brain regions using fluorescent protein-tagged viruses. They identified a route from the auditory cortex to the thalamus, which relays sensory signals, including pain, from the body. In freely moving mice, low-intensity white noise reduced the activity of neurons at the receiving end of the pathway in the thalamus.

Without sound, suppressing the pathway with light- and small molecule-based techniques mimicked the pain-blunting effects of low-intensity noise, while turning on the pathway restored animals’ sensitivity to pain.

Dr Liu said it is unclear if similar brain processes are involved in humans, or whether other aspects of sound, such as its perceived harmony or pleasantness, are important for human pain relief.

“We don’t know if human music means anything to rodents, but it has many different meanings to humans – you have a lot of emotional components,” he said.

The results could give scientists a starting point for studies to determine whether the animal findings apply to humans, and ultimately could inform development of safer alternatives to opioids for treating pain.

Source: National Institutes of Health

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Hyaluronic Acid of Little Value in Knee Osteoarthritis

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Knee pain
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Treating knee osteoarthritis with hyaluronic acid injections (known as viscosupplementation) makes almost no difference to pain or functioning and might raise risk of adverse events, suggests a review of 50 years of literature on the procedure.

Viscosupplementation has been used to treat knee osteoarthritis since the 1970s, but there are long-standing questions over its safety and efficacy.

Some 560 million people worldwide suffer from knee osteoarthritis, which involves inflammation and structural changes of the joints, resulting in joint pain and limitations to physical movement.

National and international guidelines vary in their recommendations, but most advise against the use of viscosupplementation. Researchers therefore set out to review 50 years’ worth of studies to evaluate the safety and efficacy of viscosupplementation. The studies compared viscosupplementation to placebo or no treatment.

Published in The BMJ, the main analysis of this review found that viscosupplementation was associated with a small reduction in pain compared with placebo, but the difference was tiny and was described as “clinically irrelevant.”

Their analysis showed that since 2009, there has been conclusive evidence that viscosupplementation and placebo treatment have led to the same clinical result in terms of pain reduction, meaning there is no point to having the injections.

They also found from 15 large trials on 6462 randomised participants that viscosupplementation was linked to a 49% higher risk of serious adverse events than placebo.

The authors say that based on their analysis of the studies between 2009 and 2021 alone, more than 12 000 patients were arguably unnecessarily subjected to these injections in viscosupplementation trials, which raises ethical concerns.

The study has some limitations in that it represents summary estimates and does not necessarily exclude the possibility that selected patient populations could benefit from viscosupplementation. Also, the researchers looked at adverse events that emerged rather than adverse events directly and clearly related to treatment.

However, strengths include the fact that this is the largest collection of randomised trials on viscosupplementation reported to date, which significantly decreases the risk of bias influencing the results.

As such, the authors conclude: “There is strong, conclusive evidence that among patients with knee osteoarthritis, viscosupplementation, compared with placebo, is associated with a clinically irrelevant reduction in pain intensity and with an increased risk of serious adverse events.

“The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis.”

Source: The BMJ

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New Monoclonal Antibody Eptinezumab Success in Hard-to-treat Migraine

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A trial for a new monoclonal antibody, eptinezumab, in the treatment of resistant migraine has demonstrated that it significantly reduced migraine days with acceptable safety and tolerability. The findings were published in The Lancet.

Eptinezumab, which targets calcitonin gene-related peptide, has shown migraine preventive effects starting the day following infusion and acceptable safety and tolerability in phase 3 trials, but benefits in the subpopulations of patients with previous preventive treatment failures were not examined.

In the 24-week double-blind placebo-controlled DELIVER phase 3b trial, the researchers recruited adults with episodic or chronic migraine with at least four monthly migraine days and two-to-four previous preventive treatment failures within the past 10 years. Patients were randomised to either eptinezumab 100mg, eptinezumab 300mg, or placebo. The primary efficacy endpoint was the change from baseline in mean monthly migraine days (captured using a daily electronic diary) in weeks 1–12, assessed in the full analysis set. All participants and study personnel were masked to study drug assignments. A 48-week dose-blinded extension period is ongoing.

In all, 865 patients completed the placebo-controlled period. Compared to baseline, weeks 1–12 saw reductions of 4.8 mean monthly migraine days with eptinezumab 100mg and 5.3 days at 300mg, which was a significantly less than the reduction of 2.1 days with placebo.

Adverse events were reported in 42% of patients in the eptinezumab 100mg group, 41% in the 300mg group, and in 40% in the placebo group. COVID was the most common treatment-emergent adverse event. Serious adverse events were uncommon (five [2%] of 299 in the 100mg group, seven [2%] of 294 in the 300mg group, four [1%] of 298 in the placebo group) and included anaphylactic reaction (eptinezumab 300 mg n=2) and COVID-19 (eptinezumab 100 mg n=1 and eptinezumab 300 mg n=1).

In adults with migraine and two-to-four previous preventive treatment failures, eptinezumab provided significant migraine preventive effects compared with placebo, with acceptable safety and tolerability, indicating that eptinezumab might be an effective treatment option for this patient population. The trial has a dose-blinded extension period which will provide additional long-term safety data in patients with migraine and previous preventive treatment failures.

Categories : Pain ManagementTags :

Cannabis is Moderately Effective for Chronic Pain, Review Finds

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Cannabis’s pain reduction effects appear to be less effective than previously though. Photo by Kindel Media

Cannabis product use provides modest, short-term improvements in chronic pain, albeit with some side effects, according to a large review of research on cannabis pain management. The review also revealed a general lack of high quality evidence such as randomised controlled trials (RCTs). The data will be uploaded to a web app made by Oregon Health & Science University to inform clinicians on cannabis medications.

Reporting in Annals of Internal Medicine, researchers found evidence to support a short-term benefit in treating neuropathic pain with two synthetic products with 100% tetrahydrocannabinol (THC): dronabinol (under the trade name Marinol) and nabilone (Cesamet). Another product, a sublingual spray of equal parts THC and cannabidiol (CBD), known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain. All of the products had side effects, such as nausea, sedation and dizziness.

From 3000 studies, the researchers selected RCTs or comparative observational studies of patients with chronic pain that compared cannabis products with a placebo or no treatment (that is, usual care) for at least 4 weeks of treatment or follow-up.

They ended up with a total of 25 with scientifically valid evidence – 18 RCTs and seven observational studies. Cannabinoids were categorised as high, comparable, or low THC-to-CBD ratio. The researchers found:

  • Synthetic products with high THC (> 98%) and little or no CBD: moderate improvement in pain, but greater sedation risk and possible increase in dizziness
  • Extracted products with majority THC (THC:CBD ratio ranging from 3:1 to 47:1): no significant improvement in pain, but greater study withdrawal because of adverse events and dizziness
  • Sublingual sprays with comparable THC and CBD levels: small improvement in pain but a much greater increased risk of dizziness and sedation and a moderate increase in nausea

Besides these findings, there was little evidence to support any other conclusions.

“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, PharmD, emeritus professor at OHSU. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.

“Unfortunately, there is very little scientifically valid research into most these products. We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”

“For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations,” the authors noted.

This situation makes it difficult to guide patients.

“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” said co-author Roger Chou, MD. “That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another.”

The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes ‘clinician briefs’ to help health care workers translate the clinical implications.

“This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge,” said co-author Devan Kansagara, MD, MCR, professor of medicine at OHSU.

Source: Oregon Health & Science University

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Opioid Misuse in Young Sarcoma Patients

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Nearly a quarter of young patients prescribed opioids while being treated for sarcoma continue to use opioids after treatment is completed according to findings published in CANCER, highlighting the need for safe deprescribing.

Individuals with sarcoma, a type of cancer in the bones or soft tissues, often develop damaged and fractured bones and undergo major surgical operations, and physicians may prescribe opioids for pain management. It was not clear whether doing so raises the risk for opioid misuse and overdose in these young patients. 

Melissa Beauchemin, PhD, RN, CPNP-PC, CPON, of Columbia University School of Nursing, and her colleagues sought to determine the rate of new persistent opioid use among adolescents and young adults treated for sarcoma. Persistent opioid use was defined as at least two opioid prescriptions in the 12 months after treatment was completed.  

The team drew from a large insurance claims database to analyse information on patients aged 10–26 years old who had not received prior opioids and who were diagnosed with sarcoma between 2008 and 2016.  

Among the 938 patients in the analysis, 64% received opioid prescriptions during treatment. After completing cancer therapy, 14% of patients overall and 23% of those who used opioids during treatment continued to use opioids and met the criteria for new persistent use. Being covered by Medicaid versus commercial insurance, having bone tumours versus soft tissue tumours, and receiving concurrent lorazepam (often prescribe to treat anxiety and sleeping problems) were associated with persistent opioid use. 

“Adolescents and young adults are a vulnerable population because they have benefitted less than younger and older cancer patients from recent advances. These results highlight the need to monitor young patients with sarcoma for posttreatment opioid use, given the potential negative impacts of long-term opioid use, including misuse and overdose,” said Dr Beauchemin. “Age- and developmentally appropriate strategies to effectively manage pain while minimising opioid exposure are urgently needed.” 

Dr Beauchemin stressed that for young people needing opioids for effective pain management, early and safe discontinuation of opioids should be prioritised. “Further, there is a critical need for clinical practice guidelines to support clinical decision making to safely and effectively manage pain specifically for adolescents and young adults with cancer,” she said. 

Source: Wiley

Categories : Paediatrics Pain ManagementTags :

Fall in Paediatric Post-surgical Opioid Prescriptions

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Children
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A large study has shown that opioid prescriptions for children who underwent one of eight common outpatient surgeries declined over a period of five years. These findings, reported in the journal Pediatrics, suggest that clinicians are using more discretion when considering which paediatric patients require an opioid prescription after their procedures.

Opioids are routinely prescribed after a surgery to help paediatric patients manage mild or moderate pain. However, recent studies have suggested that recovery is similar with limited or no opioid use. Additionally, opioids prescribed to children can result in respiratory depression, which causes carbon dioxide to not be expelled from the lungs properly, and the continued use of those opioids, after acute pain has resolved. Despite these findings, no prior studies had looked at recent data on national opioid trends for surgery in children in the context of whether there has been any shift away from prescribing opioids more broadly.

“Children grow throughout their childhood, and because opioids are often prescribed based on weight, we cannot assume that what is appropriate for a 5-year-old could also apply to an adolescent,” said the study’s lead author Tori N. Sutherland, MD, MPH. “In our study, we wanted to be responsible with our data and consider surgical distribution by age group.”

In this study, the researchers used data from a private insurance database to study opioid-naïve patients under the age of 18 who underwent one of eight surgical procedures between 2014 and 2019. The procedures ranged from tonsillectomies to knee surgery. The primary outcome of the study was whether a prescription for opioids was filled within 7 days of surgery, and the secondary outcome was the total amount of opioid dispensed. A total of 124 249 patients were included in the study. Patients were separated by age into adolescents, school-aged children and preschool-aged children.

The researchers found that the percentage of children who had an opioid prescription filled after their surgery fell across all three age categories. For adolescents, prescriptions dropped from 78.2% to 48%; for school-aged children, from 53.9% to 25.5%; and for preschool-aged children, from 30.4% to 11.5%. Additionally, the average morphine milligram equivalent dispensed declined by approximately 50% across all three age groups.

The researchers also found that there was a steeper decline in opioid prescriptions beginning in late 2017, first in the adolescent group and then followed by school- and preschool-aged children. This trend appeared to represent a ‘trickle down’ effect, but more research is needed to explore the difference in trends by age group.

“Our findings demonstrate that pain treatment for children and adolescents undergoing surgery has changed dramatically over the past 5 years,” said Mark Neuman, MD, senior author. “Understanding what these trends mean for patient experiences and health outcomes is a key next step.”

Source: EurekAlert!

Categories : Implants and Prostheses Pain ManagementTags :

Tiny Implantable Electrodes to Treat Drug-resistant Neuropathic Pain

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Using a rice-grain sized wireless implant to stimulate peripheral nerves from within blood vessels could potentially treat drug-resistant neuropathic pain, according to a study published in Nature Biomedical Engineering.

After receiving a grant, a team set out to create implantable, wirelessly powered nerve stimulators that can be used in place of opioids for pain management. The 1-millimetre large implants are small enough to be placed on stents and delivered within blood vessels adjacent to specific areas of the central and peripheral nervous system.

Co-principal investigator of the study, Sunil A. Sheth, MD, explained: “We’re getting more and more data showing that neuromodulation, or technology that acts directly upon nerves, is effective for a huge range of disorders—depression, migraine, Parkinson’s disease, epilepsy, dementia, etc. – but there’s a barrier to using these techniques because of the risks associated with doing surgery to implant the device, such as the risk of infection. If you can lower that bar and dramatically reduce those risks by using a wireless, endovascular method, there are a lot of people who could benefit from neuromodulation.”

Neuropathic pain can be a disabling disorder that accounts for nearly 40% of chronic pain sufferers, often leading to anxiety, depression, and opioid addiction. Previous studies showed that electrical stimulation is an effective treatment for reducing pain when doctors target the spinal cord and dorsal root ganglia (DRG), a bundle of nerves that carry sensory information to the spinal cord. However, existing DRG stimulators require invasive surgery to implant a battery pack and pulse generator.

According to the researchers, this new type of technology offers a way to perform minimally invasive bioelectronic therapy that helps with more precise placement of the implant and more predictable outcomes. The team are hoping to move forward with regulatory approval, which Dr Sheth estimates may take a few years.

Source: The University of Texas Health Science Center