Category: Pain Management

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Two Types of CBT are Equally Effective in Treating Fibromyalgia

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There does not appear to be any profound differences between so-called exposure-based CBT and traditional CBT in the treatment of fibromyalgia, according to a study led by researchers at Karolinska Institutet. Both forms of treatment produced a significant reduction in symptoms in people affected by the disease. The study, one of the largest to date to compare different treatment options for fibromyalgia, is published in the journal PAIN.

About 2–4% of people live with fibromyalgia, a long-term pain syndrome that causes great suffering for patients through widespread pain, fatigue, and stiffness in the body. There is no cure for fibromyalgia and existing drugs often have insufficient effect, raising the need for more effective treatment methods.

Cognitive behavioural therapy (CBT) has shown some effect, but there is a lack of trained CBT practitioners. There is also a lack of knowledge about which form of CBT is most effective.

The study compared two different forms of internet-delivered cognitive behavioral therapy in terms of how well they reduce the symptoms and functional impact of fibromyalgia.

In brief, exposure-based CBT involves the participant systematically and repeatedly approaching situations, activities, and stimuli that the patient has previously avoided because the experiences are associated with pain, psychological discomfort, or symptoms such as fatigue and cognitive problems.

In traditional CBT, the participant is presented with several different strategies to work on during treatment, such as relaxation, activity planning, physical exercise, or strategies for managing negative thoughts and improving sleep.

The study showed that traditional CBT was by and large equivalent to the newer treatment form of exposure-based CBT.

“This result was surprising because our hypothesis, based on previous research, was that the new exposure-based form would be more effective. Our study shows that the traditional form can provide an equally good result and thus contributes to the discussion in the field,” says Maria Hedman-Lagerlöf, licensed psychologist and researcher at the Center for Psychiatry Research at the Department of Clinical Neuroscience, Karolinska Institutet.

The randomized study involved 274 people with fibromyalgia, who were randomly assigned to be treated with traditional or exposure-based CBT.

The treatments were delivered entirely online and all participants had regular contact with their therapist.

Participants answered questions about their mood and symptoms before, during, and after treatment.

After the 10-week treatment, 60% of those who received exposure-based CBT and 59% of those who received traditional CBT reported that their treatment had helped them.

“The fact that both treatments were associated with a significant reduction in the participants’ symptoms and functional impairment and that the effects were sustained for 12 months after completion of the treatment, indicates that the internet as a treatment format can be of great clinical benefit for people with fibromyalgia,” says Maria Hedman-Lagerlöf. “This is good news because it enables more people to access treatment.”

The study is the second largest to compare different psychological treatment options for fibromyalgia, according to the researchers.

“Our study is also one of the first to compare with another active, established psychological treatment,” says Maria Hedman-Lagerlöf.

Source: Karolinska Institutet

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Patients Are Now Getting Fewer Post-op Opioids, but Decline is Slowing

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Post-surgery pain relief has shifted away from opioid-containing medications over the past seven years, but the downward trend has slowed since 2020, a new University of Michigan study shows.

Overall, the rate of surgery-related opioid prescriptions dropped by 36% from 2016 to the end of 2022, and the average amount of opioids in those prescriptions dropped by 46%, the study of pharmacy data finds.

That combination of declines means that the total amount of opioids dispensed to surgical patients in late 2022 was 66% lower compared with early 2016, according to the findings published in JAMA Network Open.

But the rate of decline was much faster before the pandemic, the researchers report after comparing surgical opioid patterns before and after 2020.

That’s even after they took into account the unusual circumstances of spring 2020, when most elective surgery temporarily stopped to free up hospital capacity for COVID-19 patients and reduce unnecessary exposure to the SARS-CoV-2 virus.

Even with the overall declines, American surgery patients in late 2022 still received the equivalent of 44 5-milligram pills of hydrocodone from pharmacies after their operations on average.

That’s far higher than what patients need for most procedures.

“These data suggest surgical teams have substantially reduced opioid prescribing, but also suggest that efforts to right-size opioid prescriptions after surgery must continue,” said Kao-Ping Chua, M.D., Ph.D., the senior author of the new study and an assistant professor of pediatrics at U-M. He worked with first author and former U-M research assistant Jason Zhang, who is now in medical school at Northwestern University.

The researchers also find that some types of surgeons have reduced the amount of opioids dispensed to patients more than others.

For instance, reductions were particularly large in cardiothoracic surgery and ophthalmology.

Orthopedic surgeons still account for more than half of all surgical opioids dispensed to American patients, even as the rate and size of prescriptions filled by their patients dropped.

Right-sizing prescribing

The authors note that surgeons should not strive to eliminate opioid prescribing altogether.

“The goal should be to ensure that opioids are only prescribed when necessary, and that the amount of opioids prescribed matches the amount that patients need,” said Zhang.

“Achieving these goals could help reduce the risk of opioid misuse, persistent opioid use, and diversion of pills to other people besides the patient.”

The potential for accidental exposure to opioids by others in the household, and interactions between opioids and other substances including alcohol and prescription drugs, are other reasons to focus on non-opioid surgical pain care.

Chua and colleagues have studied procedure-related opioid prescribing multiple times, including a recent study showing that the reduction in the rate of dental opioid prescribing has similarly slowed in recent years.

Surgical organisations and the Centers for Disease Control and Prevention have advised surgeons to rely less on opioid-based acute pain relief for their patients since the mid-2010s.

But no studies have examined surgical opioid prescribing trends using pandemic-era data.

The new study is based on data from a company called IQVIA that tracks prescriptions dispensed at 92% of US pharmacies.

Source: Michigan Medicine – University of Michigan

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One in Six Patients with Opioid Use Disorder Leave the Hospital too Early

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The number of patients admitted with opioid use disorder (OUD) and injection-related infections who left the hospital before completing treatment increased significantly between 2016 and 2020 (from 9.3% to 17%) according to analysis from researchers at the Perelman School of Medicine at the University of Pennsylvania. One in six of these patients now leave the hospital before medically advised (BMA).

The findings, published in JAMA, also reveal that the rate at which patients with any opioid-related issues (patients presenting with other issues but exhibiting opioid dependence) left the hospital BMA increased more than 50% (from 7.5 to 11.3%). In both of these groups, nearly half of BMA discharges occurred before the third day, when withdrawal symptoms are most severe. Now that fentanyl has become the dominant opioid causing overdoses, the findings illustrate the need for patient-centred care that adequately manages pain and withdrawal symptoms so that patients can complete treatment.

Approximately 500 000 patients are discharged against medical advice, or in the United States annually, and those circumstances are associated with increased likelihood of death and hospital readmission. Previous research shows that patients with addiction cite withdrawal and pain as their reason for BMA discharge.

“The rapid increase in early discharges is alarming; in 2016, less than one in ten patients admitted for OUD and injection-related infections left the hospital before their care team considered it safe. By 2020, one in six were leaving early,” said lead author Ashish Thakrar, MD. “What’s more, since the study period ended, the COVID-19 pandemic caused the opioid crisis to escalate, underscoring just how urgent it is to understand how we might be able to reverse this trend and get patients the treatment they need.”

Using nationally representative data from the National Readmissions Database, researchers compared the rate of discharge BMA in patients admitted for OUD to the BMA discharge rate for non-opioid admissions. They also evaluated changes in the proportion of BMA discharges before the third admission day, when opioid withdrawal is most severe, and changes in the proportion of discharges BMA in patients with stimulant use disorder.

They identified opioid-related admissions as those with opioid use, dependence, abuse, or overdose. To account for patients who were more likely to have severe OUD and fentanyl use, they also included patients with OUD and an injection related infections, such as bacteraemia, endocarditis, or osteomyelitis.

Between 2016 and 2020, they found that the number of patients admitted with OUD and injection-related infections who left the hospital BMA increased 82%, from 9.3% to 17%. They also found that the discharge BMA rate for all opioid-related admissions increased 50% during this period, from 7.5% to 11.3%. The proportion of BMA discharges occurring before the third day also increased for individuals with OUD and an injection-related infection, from 42.6%, to 48%.

In contrast, the BMA rate increased only marginally for non-opioid mental health or substance use admissions, and all non-opioid admissions (from 3.1 to 3.5%, and 1.1 to 1.5%, respectively).

“These data didn’t allow us to discern which type of opioid that individuals were using when admitted for OUD, but we know that fentanyl, an opioid 25 to 50 times more potent than heroin, has spread in unregulated drug supplies and is now involved in 88 percent of opioid overdoses in the US. Withdrawal symptoms from fentanyl are more difficult to manage than from other opioids like heroin and oxycodone,” said Thakrar. “This study illustrates why we need more research on how to manage individuals withdrawing from fentanyl and other substances in the unregulated drug supply.”

“The drugs that individuals are using have changed over the past decade, and how we treat them should change, too,” said senior author M. Kit Delgado, MD, MS. “Health systems can expand the use of interventions that are already proven to treat withdrawal and reduce but not widely used, such as medications like buprenorphine and methadone.”

Thakrar and Delgado also suggest that hospitals could be incentivised to reduce discharges BMA and to support specialty services such as addiction consult services that have been proven to reduce BMA discharges and that can reduce the risks of future readmission or death.

Source: Penn University Medicine

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At Last, Objective Evidence for the Involvement of Neck Muscles in Headaches

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Researchers have identified objective evidence of how the neck muscles are involved in primary headaches. The study findings, being presented at the annual meeting of the Radiological Society of North America (RSNA), could lead to better treatments.

The distinct underlying causes of primary headaches, comprising tension-type headaches and migraines, are still not fully understood.

“Our imaging approach provides first objective evidence for the very frequent involvement of the neck muscles in primary headaches, such as neck pain in migraine or tension-type headache, using the ability to quantify subtle inflammation within muscles,” said Nico Sollmann, MD, PhD, resident at University Hospital Ulm and University Hospital Rechts der Isar in Munich, Germany.

In tension-type headaches there is often the perception of a tightening in the head and mild to moderate dull pain on both sides of the head. While these headaches are typically associated with stress and muscle tension, their exact origin is not fully understood.

Migraines are characterised by a severe throbbing pain and generally occur or are worse on one side of the head. Migraines may also cause nausea, weakness and light sensitivity.

Neck pain is commonly associated with primary headaches but there are no objective biomarkers for myofascial involvement. Myofascial pain is associated with inflammation or irritation of muscle or of the connective tissue, known as fascia, that surrounds the muscle.

For the study, Dr Sollmann and colleagues aimed to investigate the involvement of the trapezius muscles in primary headache disorders by quantitative magnetic resonance imaging (MRI) and to explore associations between muscle T2 values and headache and neck pain frequency.

The prospective study recruited 50 participants, mostly women, ranging in age from 20 to 31 years old. Of the participants, 16 had tension-type headache, and 12 had tension-type headache plus migraine episodes. The groups were matched with 22 healthy controls.

All participants underwent 3D turbo spin-echo MRI. The bilateral trapezius muscles were manually segmented, followed by muscle T2 extraction.

Associations between muscle T2 values and the presence of neck pain, number of days with headache, and number of myofascial trigger points as determined by manual palpation of the trapezius muscles were analysed (adjusting for age, sex and body mass index).

The tension-type headache plus migraine group demonstrated the highest muscle T2 values. Muscle T2 was significantly associated with the number of headache days and the presence of neck pain.

The increased muscle T2 values could be interpreted as a surrogate of inflammation arising from the nervous system and increased sensitivity of nerve fibres within myofascial tissues.

“The quantified inflammatory changes of neck muscles significantly correlate with the number of days lived with headache and the presence of subjectively perceived neck pain,” Dr Sollmann said.

“Those changes allow us to differentiate between healthy individuals and patients suffering from primary headaches.”

Muscle T2 mapping could be used to stratify patients with primary headaches and to track potential treatment effects for monitoring.

“Our findings support the role of neck muscles in the pathophysiology of primary headaches,” Dr Sollmann said. “Therefore, treatments that target the neck muscles could lead to a simultaneous relief of neck pain, as well as headache.”

Dr Sollmann pointed out that non-invasive treatment options that directly target the site of pain in the neck muscles could be highly effective and safer than systemic drugs.

“Our imaging approach with delivery of an objective biomarker could facilitate therapy monitoring and patient selection for certain treatments in the near future,” he added.

Source: Radiological Society of North America

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Dependence on Pain Medication is on the Rise

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Dependence on pain medication is on the rise due to lack of vigilance by medical professionals, according to a new study from the University of Surrey. In the paper published in the journal Pain and Therapy, patients dependent on pain medication describe feelings of ‘living in a haze’ and being ignored and misunderstood by the medical profession.

In the first study of its kind in the UK, Louise Norton and Dr Bridget Dibb from the University of Surrey investigated the experiences of patients dependent on medication for chronic pain. Pharmacological treatment for chronic pain usually involves potentially addictive substances such as non-steroidal anti-inflammatory drugs, gabapentinoids, and opioids. Increased prescription levels of such pain relief medications have been associated with heightened levels of overdose and misuse.

Dr Bridget Dibb, Senior Lecturer in Health Psychology at the University of Surrey, said: “An increasing number of people are experiencing chronic pain, which can interfere with their daily life and lead to depression and anxiety. Medication can help alleviate pain and return a sense of normalcy to a person’s life; however, there is a risk of dependence, which can potentially cause damage to vital organs, including the liver and kidneys.

“The first step to tackle this problem is to learn more about a person’s experience, how they perceive their dependence and how they interact with others, including the medical profession.”

To learn more, interviews were carried out with nine participants who had become dependent on pain medication. Participants spoke about how their dependence on pain medication resulted in them feeling not fully present and removed from their lives due to the side effects of the treatment. Many also expressed frustration about the lack of alternative treatment options available on the NHS to manage their pain, with medications being too readily prescribed.

The majority of participants also spoke about their negative interactions with medical professionals, with some attributing the cause of their dependence on them. Many believed a lack of continuity between doctors led to missed opportunities in spotting their dependence, enabling it to continue.

Louise Norton added: “Relationships with medical professionals substantially affect the experiences of those with painkiller dependence. Doctors can often be seen as authority figures due to their expertise and so patients may be apprehensive to question their treatment options. However, through providing patients with thorough information, doctors can enable more shared-decision making in which patients feel better supported and equipped to manage their chronic pain.”

Researchers noted participants felt stigmatised when speaking with others about their dependence due to a lack of understanding about their reliance to prescribed pain medications. Such interactions left participants feeling ashamed and critical of themselves.

Dr Dibb added: “Those with a dependence on prescription painkillers not only have to navigate their reliance on the medication but the shame and guilt associated with such a need. Combining this with feelings of being misunderstood and ignored by medical professionals, they have a lot of emotional needs to be managed alongside their physical pain. To prevent this from happening medical professionals need to be more vigilant when prescribing medication and ensure that their patients are fully aware of the risk of dependence before they begin treatment.”

Source: University of Surrey

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New Compound Outperforms Gabapentin for Pain Relief

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A new compound reversed four types of chronic pain in animal studies, according to new research published online in the Proceedings of the National Academy of Sciences (PNAS). It outperformed gabapentin without troublesome side effects, providing a promising candidate for treating pain.

Researchers led by NYU College of Dentistry’s Pain Research Center developed this small molecule, which binds to an inner region of a calcium channel to indirectly regulate it.

Calcium channels play a central role in pain signaling, in part through the release of neurotransmitters such as glutamate and GABA – “the currency of the pain signal,” according to Rajesh Khanna, director of the NYU Pain Research Center and professor of molecular pathobiology. The Cav2.2 (or N-type) calcium channel is the target for three clinically available drugs, including gabapentin and pregabalin, which are widely used to treat nerve pain and epilepsy.

Gabapentin mitigates pain by binding to the outside of the Cav2.2 calcium channel, affecting the channel’s activity. However, like many pain medications, gabapentin use often comes with side effects.

“Developing effective pain management with minimal side effects is crucial, but creating new therapies has been challenging,” said Khanna, the senior author of the PNAS study. “Rather than directly going after known targets for pain relief, our lab is focused on indirectly targeting proteins that are involved in pain.”

Inside the channel

Khanna has long been interested in a protein called CRMP2, a key regulator of the Cav2.2 calcium channel that binds to the channel from the inside. He and his colleagues previously discovered a peptide derived from CRMP2 that could uncouple CRMP2 from the calcium channel. When this peptide – calcium channel-binding domain 3 (CBD3) – was delivered to cells, it acted as a decoy, blocking CRMP2 from binding to the inside of the calcium channel. This resulted in less calcium entering the calcium channel and less neurotransmitter release, which translated to less pain in animal studies.

Peptides are difficult to synthesise as drugs because they are short-acting and easily degrade in the stomach, so the researchers sought to create a small molecule drug based on CBD3. Starting with the 15 amino acids that make up the CBD3 peptide, they honed in on two amino acids that studies showed were responsible for inhibiting calcium influx and mitigating pain.

“At that point, we realised that these two amino acids could be the building blocks for designing a small molecule,” said Khanna.

From 27 million to one

In collaboration with colleagues at the University of Pittsburgh, the researchers ran a computer simulation that screened a library of 27 million compounds to look for a small molecule that would “match” the CBD3 amino acids.

The simulation narrowed the library down to 77 compounds, which the researchers experimentally tested to see if they lessened the amount of calcium influx. This further pared the pool down to nine compounds, which were assessed using electrophysiology to measure decreases in electrical currents through the calcium channels.

One compound, which the researchers named CBD3063, emerged as the most promising candidate for treating pain. Biochemical tests revealed that CBD3063 disrupted the interaction between the CaV2.2 calcium channel and CRMP2 protein, reduced calcium entering the channel, and lessened the release of neurotransmitters.

“Many scientists have screened the same library of compounds, but have been trying to block the calcium channel from the outside. Our target, these two amino acids from CRMP2, is on the inside of the cell, and this indirect approach may be the key to our success,” said Khanna.

Four labs, four types of pain

Khanna’s lab then tested CBD3063 with mouse models for pain related to injury. The compound was effective in alleviating pain in both male and female mice – and notably, in a head-to-head test with the drug gabapentin, the researchers needed to use far less CBD3063 (1–10mg) than gabapentin (30 mg) to reduce pain.

To explore whether CBD3063 helped with different types of chronic pain, Khanna partnered with researchers at Virginia Commonwealth University, Michigan State University, and Rutgers University. Collaborators ran similar studies administering CBD3063 to treat animal models of chemotherapy-induced neuropathy, inflammatory pain, and trigeminal nerve pain – all successfully reversing pain, similar to gabapentin.

But unlike gabapentin, the use of CBD3063 did not come with side effects, including sedation, changes to cognition such as memory and learning, or changes to heart rate and breathing.

What’s next

The researchers are continuing to study CBD3063, refining its chemical composition and running additional tests to study the compound’s safety and assess if tolerance develops.

Long-term, they hope to bring a CBD3063-derived drug to clinical trials in an effort to offer new options for safe and effective pain relief.

“Identifying this first-in-class small molecule has been the culmination of more than 15 years of research. Though our research journey continues, we aspire to present a superior successor to gabapentin for the effective management of chronic pain,” said Khanna.

Source: New York University

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Only 30% of Adults Discuss OTC Pain Relievers with Doctors Despite Hypertension Risk

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Only about 30% of US adults have spoken with their health care professional about the adverse effects some over-the-counter (OTC) pain relievers can have on blood pressure. The findings are part of a recent online poll commissioned by the American Heart Association.

Some pain relievers may raise blood pressure, according to the American Heart Association’s most recent Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure. 

“It’s paramount that people who have high blood pressure, or are at risk for it, understand the effects associated with some over-the-counter pain relievers,” said Mitchell S. V. Elkind, MD, MS, FAHA, chief clinical science officer of the American Heart Association and a tenured professor of neurology and epidemiology at Columbia University. “A conversation with a health care professional about pain relief options is essential to preventing and managing high blood pressure.”

High blood pressure affects almost half of all people in the US. According to the American Heart Association’s recent poll, of those who have been diagnosed with high blood pressure, white and Asian adults (40%) are significantly less likely than Black (54.2%) and Hispanic (54.1%) adults to have ever discussed the effect some pain relievers have on blood pressure with a health care professional.
“Some over-the-counter pain relievers are safer than others,” added Elkind. “A conversation with a health care professional regularly about medications you or a loved one takes is an important step in finding safe options and controlling blood pressure.”

The poll conducted by Big Village, a collaborative and consultative research firm, also looked at how often people used OTC pain relievers. Of the close to 3000 US adults aged 18 and older surveyed, nearly 50% took medication for pain once a week or more. Adults aged 45-54 take them most frequently of all age groups polled. Additional findings include:

  • Gen X, people born from 1965 to 1980, are significantly more likely than other generations to take OTC pain relievers multiple times a day, but only 41% of Gen X would initially ask a health care professional for alternative pain relief even if they knew some OTC pain relievers can raise a person’s blood pressure.
  • Gen Z, people born from 1997 to 2012, are significantly less likely (30.5%) than any other generation to initially ask their health care professional for alternative pain relief if they knew some OTC pain relievers can raise a person’s blood pressure.
  • 61% of all respondents had not discussed the effect some over-the-counter pain relievers have on blood pressure with a health care professional.
  • 22% would research an alternative pain reliever online, second only to discussing with a health care professional.

Source: American Heart Association

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How Sleep Disruption Can Make Pain Feel Worse

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People often experience headaches and body pain after a lack of sleep, but the mechanisms behind this phenomenon are unclear. A new study published in Nature Communications reveals that a certain endocannabinoid neurotransmitter plays a major role.

The animal-based study, led by investigators at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), found that the heightened pain sensitivity than can result from chronic sleep disruption (CSD) – or CSD-induced hyperalgaesia – involved signalling from a part of a brain known as the thalamic reticular nucleus (TRN).

Analyses of metabolites showed that the level of N-arachidonoyl dopamine (NADA), a type of neurotransmitter called an endocannabinoid, decreased in the TRN as a result of sleep deprivation.

Activity of the cannabinoid receptor 1, which is involved in controlling pain perception, also decreased in the thalamic reticular nucleus after CSD.

Administering NADA to the TRN reduced CSD-induced hyperalgaesia in mice.

This beneficial effect of administered NADA could be countered by blocking the cannabinoid receptor 1, suggesting that both the receptor and NADA play a role in pain sensitivity due to sleep deprivation.

“We provide a mechanism as to how sleep disruption leads to exaggerated pain, suggesting that harnessing the endocannabinoid system might break the vicious cycle between pain and sleep loss,” says co-senior author Shiqian Shen, MD, the clinical director of MGH’s Tele Pain Program.

Source: Massachusetts General Hospital

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No Increase in Post-surgical Pain Seen with Opioid Limits

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Concerns that surgery patients would have a more difficult recovery if their doctors had to abide by a five-day limit on opioid pain medication prescriptions did not play out as expected, finds a study published in JAMA Health Forum.

Instead, the University of Michigan-led researchers found that , after the largest insurer in that US state put the limit in place, patient-reported pain levels and satisfaction didn’t change at all for adults who had their appendix or gallbladder removed, a hernia repaired, a hysterectomy or other common operations.

At the same time, the amount of opioid pain medication patients covered by that insurer received dropped immediately after the limit went into effect. On average, patients having these operations received about three fewer opioid-containing pills.

The study, which merges two statewide databases on patients covered by Blue Cross Blue Shield of Michigan, is the first large study to evaluate whether opioid prescribing limits change patient experience after surgery.

Measuring the impact of limits from patients’ perspectives

The BCBSM limit of five days’ supply, which went into effect in early 2018, is even stricter than the seven-days’ supply limit put in place a few months later by the state of Michigan.

Other major insurers and states have also implemented limits, most of which allow are seven-day limits.

Limits are designed to reduce the risk of long-term opioid use and opioid use disorder, as well as to reduce the risk of accidental overdose and the risk of unauthorized use of leftover pills.

“Opioid prescribing limits are now everywhere, so understanding their effects is crucial,” said lead author Kao-Ping Chua, MD, PhD.

“We know these limits can reduce opioid prescribing, but it hasn’t been clear until now whether they can do so without worsening patient experience.”

He noted that even the 15% of patients who had been taking opioids for other reasons before having their operations showed neither an increase in pain nor a decrease in satisfaction after the limit was put in place, even though opioid prescribing for these patients decreased.

That decrease was actually contrary to the intent of the limit, which was only designed to reduce prescribing to patients who hadn’t taken opioids recently.

How the study was done

For the new study, Chua and colleagues used data from the Michigan Surgical Quality Collaborative, which collects data on patients having common operations at 70 Michigan hospitals. The MSQC surveys patients about their pain, level of satisfaction and level of regret after their operations.

The team paired anonymized MSQC data with data on controlled substance prescription fills from Michigan state’s prescription drug monitoring programme, called MAPS.

In all, they were able to look at opioid prescribing and patient experience data from 1,323 BCBSM patients who had common operations in the 13 months before the five-day limit went into effect, and 4,722 patients who had operations in the 20 months after the limit went into effect.

About 86% of both groups were non-Hispanic white, patients’ average age was just under 49,  and just under a quarter of both groups had their operations on an emergency or urgent basis. Just under half were admitted to the hospital for at least one night.

About 27% of both groups had their gallbladders taken out laparoscopically, and a similar percentage had minor hernia repairs.

About 10% had an appendectomy done laparoscopically, and a similar percentage had laparoscopic hysterectomies.

The rest had more invasive procedures, like open hysterectomies major hernia repairs, or colon removal. 

The percentage of prescribers who prescribed opioids to their patients having these operations did not change, but the percentage of patients who filled a prescription for an opioid did, possibly because pharmacists rejected prescriptions that weren’t compliant with the BCBSM limit, Chua speculates.

Jennifer Waljee, MD, MPH, MS, senior author of the study, notes that the MSQC database doesn’t include all types of procedures, such as knee replacements and spine surgery, which typically require larger postoperative opioid prescriptions because of their associated pain.

She indicated that it’s important to understand the impact of opioid prescribing limits on the experiences of such patients, because limits have the most potential to worsen pain for these individuals. 

“Opioid prescribing limits may not worsen patient experience for common, less-invasive procedures like those we studied, because opioid prescriptions for most of these procedures were already under the maximum allowed by limits.

“But this may not be the case for painful operations where opioid prescribing was suddenly cut from an 8- to 10-day supply to a 5-day supply,” said Waljee.

She added, “The message of this study is not that we can simply go to five days’ supply across the board for operations.

“We need to understand the effects of these limits across a broad range of procedures and patients given how much pain needs vary in order to right size prescribing to patient need without resulting in additional harms.”

Source: University of Michigan

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Neanderthal Gene Variants Associated with Greater Sensitivity to Some Types of Pain

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People who carry three gene variants that have bene inherited from Neanderthals are more sensitive to some types of pain, according to a new study co-led by UCL researchers. The findings, published in Communications Biology, are the latest findings to show how past interbreeding with Neanderthals has influenced the genetics of modern humans.

The researchers found that people carrying three so-called Neanderthal variants in the gene SCN9A, which is implicated in sensory neurons, are more sensitive to pain from skin pricking after prior exposure to mustard oil.

Previous research has identified three variations in the SCN9A gene – known as M932L, V991L, and D1908G – in sequenced Neanderthal genomes and reports of greater pain sensitivity among humans carrying all three variants. However, prior to this study the specific sensory responses affected by these variants was unclear.

An international team measured the pain thresholds of 1963 people from Colombia in response to a range of stimuli.

The SCN9A gene encodes a sodium channel that is expressed at high levels in sensory neurons that detect signals from damaged tissue. The researchers found that the D1908G variant of the gene was present in around 20% of chromosomes within this population and around 30% of chromosomes carrying this variant also carried the M932L and V991L variants.

The authors found that the three variants were associated with a lower pain threshold in response to skin pricking after prior exposure to mustard oil, but not in response to heat or pressure. Additionally, carrying all three variants was associated with greater pain sensitivity than carrying only one.

When they analysed the genomic region including SCN9A using genetic data from 5971 people from Brazil, Chile, Colombia, Mexico and Peru, the authors found that the three Neanderthal variants were more common in populations with higher proportions of Native American ancestry, such as the Peruvian population, in which the average proportion of Native American ancestry was 66%.

The authors propose that the Neanderthal variants may sensitise sensory neurons by altering the threshold at which a nerve impulse is generated. They speculate that the variants may be more common in populations with higher proportions of Native American ancestry as a result of random chance and population bottlenecks that occurred during the initial occupation of the Americas. Although acute pain can moderate behaviour and prevent further injury, the scientists that say additional research is needed to determine whether carrying these variants and having greater pain sensitivity may have been advantageous during human evolution.

Diagram comparing the nose shape of a Neanderthal with that of a modern human by Dr Macarena Fuentes-Guajardo.

Previous research by co-corresponding author Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) has shown that humans also inherited some genetic material from Neanderthals affecting the shape of our noses.

Dr Adhikari commented: “In the last 15 years, since the Neanderthal genome was first sequenced, we have been learning more and more about what we have inherited from them as a result of interbreeding tens of thousands of years ago.

“Pain sensitivity is an important survival trait that enables us to avoid painful things that could cause us serious harm. Our findings suggest that Neanderthals may have been more sensitive to certain types of pain, but further research is needed for us to understand why that is the case, and whether these specific genetic variants were evolutionarily advantageous.”

First author Dr Pierre Faux (Aix-Marseille University and University of Toulouse) said: “We have shown how variation in our genetic code can alter how we perceive pain, including genes that modern humans acquired from the Neanderthals. But genes are just one of many factors, including environment, past experience, and psychological factors, which influence pain.”

Source: University College London