Category: Pain Management

Categories : Pain ManagementTags :

Researchers Delve into the Roots of Chronic Pain

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A team of researcher have identified a new function for the PIEZO2 protein – in mediating chronic pain hypersensitivity. The research suggests a new target for analgesics and potentially explains why pain medications that target voltage gated sodium channels have been disappointing as clinical targets. The study, led by Oscar Sánchez-Carranza in Professor Gary Lewin’s lab at the Max Delbrück Center, was published in the journal Brain.

“There’s a good correlation between chronic pain and the sensitisation of pain receptors, called nociceptors, in humans,” says Lewin. “This study implicates the PIEZO2 channel as a critical mediator of sensory signals that maintain chronic pain.”

PIEZO2 protein forms an ion channel in human sensory receptors. Previous studies have shown that the ion channel is involved in communicating the sense of touch to the brain. People with “loss-of-function” mutations in the PIEZO2 gene are hypo-sensitive to gentle touch or vibration. By contrast, patients with “gain-of-function mutations” in PIEZO are often diagnosed with complex developmental disorders. But whether gain-of-function mutations are responsible for mechanical hypersensitivity had never been proven.

Mutation dramatically sensitises nociceptors

To study the connection, Sánchez-Carranza created two strains of so called “gain-of-function” mice, each carrying a different version of a mutated PIEZO2 gene. He expected to find the touch receptors of these mice to be highly sensitive. In cell biology experiments his team has found that PIEZO2 mutations have a powerful effect on the activity of the ion channel. One mutation, for example, causes the channel to open with 10 times less force compared to normal non-mutated channels.

Using electrophysiological methods developed in the Lewin lab, Sánchez-Carranza and his colleagues measured electrical activity in sensory neurons isolated from the transgenic mice. They found that in addition to sensitising touch receptors as expected, the mutations made nociceptive receptors – neurons that detect painful mechanical stimuli – dramatically more sensitive to mechanical stimuli.

Moreover, the researchers found that the nociceptors were activated by mechanical stimuli that would normally be experienced as light touch.

“You pretty much need to crush the skin to activate nociceptors,” Sánchez-Carranza explains. But the nociceptors from the transgenic mice were triggered by levels of mechanical force that would normally be perceived as a touch. They were incredibly sensitive.”

That a single mutation in PIEZO2 was enough to change the physiology of the nociceptors from one type of neuron to another, was especially surprising, says Lewin. More significantly, when the stimulus was removed, the neurons kept firing. The study is the first time that anyone has linked gain-of-function mutations in the PIEZO2 gene to pain receptors.

PIEZO2 might be involved in pain syndromes like fibromyalgia

Clinical studies have shown that in patients with chronic pain syndromes such as fibromyalgia and small fibre neuropathies, C-fibre nociceptors, which are the sensory receptors that initiate pain, are hyperactive. When researchers have recorded the activity of nociceptors in such people, they found that the they were active in the absence of any mechanical stimulus. But the mechanism was not clear.

“We show that just by changing one amino acid in PIEZO2, we can actually mimic a lot of what happens in chronic pain in the C-fibres,” says Lewin. In humans, “PIEZO2 might be involved in many of these pathologies.” Nociceptive neurons are the largest population of sensory neurons that innervate the skin – humans have four times more pain receptors in the skin than touch receptors.

Up to 20% of the adult population suffers from chronic pain, according to a 2023 study by the U.S. National Institutes of Health, which is poorly treated with existing medications. The same NIH study found that two thirds of people who reported chronic pain in 2019 were still suffering one year later.

The findings suggest that a particular aspect of the PIEZO2 channels mechanism of opening could be targeted by new pain medications. Much effort on developing new analgesics has focused on voltage gated sodium channels with limited success, says Lewin. “By addressing the root cause of nociceptor sensitisation, new drugs could provide better relief for chronic pain sufferers.”

Source: Max Delbrück Center

Categories : Neurology Pain ManagementTags :

Researchers Figure out How Propofol Makes Patients Lose Consciousness

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There are many drugs that anaesthesiologists can use to induce unconsciousness in patients. Exactly how these drugs cause the brain to lose consciousness has been a longstanding question, but MIT neuroscientists have now answered that question for the commonly used drug propofol.

Using a novel technique for analysing neuron activity, the researchers discovered that the drug propofol induces unconsciousness by disrupting the brain’s normal balance between stability and excitability. The drug causes brain activity to become increasingly unstable, until the brain loses consciousness.

“The brain has to operate on this knife’s edge between excitability and chaos. It’s got to be excitable enough for its neurons to influence one another, but if it gets too excitable, it spins off into chaos. Propofol seems to disrupt the mechanisms that keep the brain in that narrow operating range,” says Earl K. Miller, the Picower Professor of Neuroscience and a member of MIT’s Picower Institute for Learning and Memory.

The new findings, published in Neuron, could help researchers develop better tools for monitoring patients as they undergo general anaesthesia.

Miller and Ila Fiete, a professor of brain and cognitive sciences, the director of the K. Lisa Yang Integrative Computational Neuroscience Center (ICoN), and a member of MIT’s McGovern Institute for Brain Research, are the senior authors of the new study. MIT graduate student Adam Eisen and MIT postdoc Leo Kozachkov are the lead authors of the paper.

Losing consciousness

Propofol is a drug that binds to GABA receptors in the brain, inhibiting neurons that have those receptors. Other anaesthesia drugs act on different types of receptors, and the mechanism for how all of these drugs produce unconsciousness is not fully understood.

Miller, Fiete, and their students hypothesised that propofol, and possibly other anaesthesia drugs, interfere with a brain state known as “dynamic stability.” In this state, neurons have enough excitability to respond to new input, but the brain is able to quickly regain control and prevent them from becoming overly excited.

Previous studies of how anaesthesia drugs affect this balance have found conflicting results: Some suggested that during anaesthesia, the brain shifts toward becoming too stable and unresponsive, which leads to loss of consciousness. Others found that the brain becomes too excitable, leading to a chaotic state that results in unconsciousness.

Part of the reason for these conflicting results is that it has been difficult to accurately measure dynamic stability in the brain. Measuring dynamic stability as consciousness is lost would help researchers determine if unconsciousness results from too much stability or too little stability.

In this study, the researchers analysed electrical recordings made in the brains of animals that received propofol over an hour-long period, during which they gradually lost consciousness. The recordings were made in four areas of the brain that are involved in vision, sound processing, spatial awareness, and executive function.

These recordings covered only a tiny fraction of the brain’s overall activity, so to overcome that, the researchers used a technique called delay embedding. This technique allows researchers to characterize dynamical systems from limited measurements by augmenting each measurement with measurements that were recorded previously.

Using this method, the researchers were able to quantify how the brain responds to sensory inputs, such as sounds, or to spontaneous perturbations of neural activity.

In the normal, awake state, neural activity spikes after any input, then returns to its baseline activity level. However, once propofol dosing began, the brain started taking longer to return to its baseline after these inputs, remaining in an overly excited state. This effect became more and more pronounced until the animals lost consciousness.

This suggests that propofol’s inhibition of neuron activity leads to escalating instability, which causes the brain to lose consciousness, the researchers say.

Better anesthesia control

To see if they could replicate this effect in a computational model, the researchers created a simple neural network. When they increased the inhibition of certain nodes in the network, as propofol does in the brain, network activity became destabilized, similar to the unstable activity the researchers saw in the brains of animals that received propofol.

“We looked at a simple circuit model of interconnected neurons, and when we turned up inhibition in that, we saw a destabilization. So, one of the things we’re suggesting is that an increase in inhibition can generate instability, and that is subsequently tied to loss of consciousness,” Eisen says.

As Fiete explains, “This paradoxical effect, in which boosting inhibition destabilises the network rather than silencing or stabilising it, occurs because of disinhibition. When propofol boosts the inhibitory drive, this drive inhibits other inhibitory neurons, and the result is an overall increase in brain activity.”

The researchers suspect that other anesthetic drugs, which act on different types of neurons and receptors, may converge on the same effect through different mechanisms – a possibility that they are now exploring.

If this turns out to be true, it could be helpful to the researchers’ ongoing efforts to develop ways to more precisely control the level of anaesthesia that a patient is experiencing. These systems, which Miller is working on with Emery Brown, the Edward Hood Taplin Professor of Medical Engineering at MIT, work by measuring the brain’s dynamics and then adjusting drug dosages accordingly, in real-time.

“If you find common mechanisms at work across different anaesthetics, you can make them all safer by tweaking a few knobs, instead of having to develop safety protocols for all the different anaesthetics one at a time,” Miller says. “You don’t want a different system for every anesthetic they’re going to use in the operating room. You want one that’ll do it all.”

The researchers also plan to apply their technique for measuring dynamic stability to other brain states, including neuropsychiatric disorders.

“This method is pretty powerful, and I think it’s going to be very exciting to apply it to different brain states, different types of anaesthetics, and also other neuropsychiatric conditions like depression and schizophrenia,” Fiete says.

Source: MIT

Categories : Paediatrics Pain ManagementTags :

Many Youths Continue to Take Post-surgery Opioids for Months

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A multi-institutional study found that 1 in 6 youths fill an opioid prescription prior to surgery, and 3% of patients were still filling opioid prescriptions three to six months after surgery, indicating persistent opioid use and possible opioid dependence. The study underscores that more guidance is needed to steer clinicians away from prescribing opioids when they are not likely to be needed and recognising patient-specific risk factors for persistent opioid use. The findings were recently published by the journal JAMA Network Open.

Approximately 1.4 million youths undergo surgery in the United States each year, and there is concern that they remain highly susceptible to opioid-related harms. While significant strides have been made in reducing prescriptions for opioids, it is important for clinicians to consider adolescent patients who may be at risk for developing an addiction to opioids due to a range of genetic, neurobiological and social vulnerabilities.  Prior to this study, little was known about risks for persistent opioid use among adolescents and the timing of initial and refill of opioid prescriptions.

“While prior analyses have shown a decline in opioid prescriptions in general, following surgical opioid prescribing recommendations remains a critical issue, especially for adolescents who are more inclined to engage in risk-taking behaviour,” said first study author Tori N. Sutherland, MD, MPH, an attending anaesthesiologist at Children’s Hospital of Philadelphia. “Our study found that these patients are still filling prescriptions that are either not recommended or are in excess of what they may need. They are also filling prescriptions up to two weeks before surgeries not associated with severe pre-operative pain, putting young patients at risk for developing persistent use throughout their lives as they transition into adulthood.”

Using a national insurance database of privately insured patients, the researchers looked at patients between 11 and 20 who underwent 22 surgical procedures that were either common or associated with severe postoperative pain requiring opioids for initial pain management. The patients had not taken opioids prior to their surgeries.

Of more than 100 000 patients, 46 951 (46.9%) patients filled a prescription for opioids, and 7587 (16.2%) of those had a prescription filled up to two weeks prior to surgery for procedures unlikely to be associated with severe preoperative pain. In this group, 6467 (13.8%) patients filled a second prescription for opioids, and 1216 (3.0%) patients filled prescriptions between 91 and 180 days after their surgical procedure.

One of the most important findings was that severe pain following a surgical procedure was not associated with persistent opioid use.  However, patients with pre-existing chronic pain, who often underwent procedures associated with mild or moderate pain that could be managed with non-opioid medications, had increased odds of developing persistent opioid use.

“We believe this study underscores the need for establishing a standard of care for patients who undergo these procedures,” said senior study author Scott Hadland, MD, MPH, Chief of Adolescent and Young Adult Medicine at Mass General for Children and Associate Professor of Pediatrics at Harvard Medical School. “Effective pain management is critical and sometimes require opioids, but clinicians also need to make sure they are doing everything possible not to further contribute to the opioid addiction crisis, particularly with young patients.”

Source: Children’s Hospital of Philadelphia

Categories : Pain Management Surgeries & ProceduresTags :

A Handful of Procedures Account for Large Share of Post-surgical Opioids

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A handful of common surgical procedures account for large shares of all opioids dispensed after surgery in children and adults, according to two studies recently published by researchers at the University of Michigan.

The studies, published this week in Pediatrics and JAMA Network Open, report that the top three procedures for children ages 0–11 account for 59% of opioids dispensed after surgery (tonsillectomies and adenoidectomies 50%, upper extremity fractures 5% and removal of deep implants 4%). Among those ages 12–21, the top three procedures account for about a third of post-surgery opioid prescriptions (tonsillectomies and adenoidectomies 13%, knee arthroscopies 13% and caesarean deliveries 8%).

For adults ages 18–44, C-sections account for the highest share of opioids dispensed post-surgery (19%), followed by hysterectomies (7%) and knee arthroscopies (6%). Among those ages 45-64, four of the top five procedures were orthopaedic procedures, collectively accounting for 27% of total opioid prescriptions dispensed after surgery.

“Our findings suggest that surgical opioid prescribing is highly concentrated among a small group of procedures. Efforts to ensure safe and appropriate surgical opioid prescribing should focus on these procedures,” said Kao-Ping Chua, lead author of the study in Pediatrics, assistant professor at the U-M Medical School and School of Public Health, and co-director of the Research and Data Domain at the U-M Opioid Research Institute.

To conduct the study, the researchers developed an algorithm to identify 1082 major surgical procedures using procedure codes, a medical classification tool used to identify specific surgical, medical or diagnostic interventions. The algorithm was then applied to identify privately and publicly insured children and adults undergoing surgery from Dec. 1, 2020 through Nov. 30, 2021.

The information was organized through a novel system developed by the study team, which allowed them to connect different sets of data that had previously been seen as unrelated. This new method allows for improved comparability and contrast, according to lead investigators.

In addition to determining which procedures accounted for the highest shares of opioids, the researchers also examined the size of opioid prescriptions for each procedure. For many procedures, prescriptions were far larger than the amount patients typically need for a particular procedure.

“Our findings suggest that there are important opportunities to reduce surgical opioid prescribing without compromising pain control,” said Dominic Alessio-Bilowus, lead author of the paper focused on adults published in JAMA Network Open and a medical student at Wayne State University who just completed a research year at U-M.

Source: University of Michigan

Categories : Exercise Pain ManagementTags :

Walking is Highly Effective for Stopping Low Back Pain from Returning

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New research from Macquarie University’s Spinal Pain Research Group shows that walking has the potential to change the way low back pain is managed, making effective interventions accessible to more people than ever before. The results of the trial, which combined walking with education, are published in The Lancet.

About 800 million people worldwide have low back pain, which is a leading cause of disability and reduced quality of life. Recurrences of low back pain are very common, with seven in 10 people who recover from an episode going on to have a recurrence within a year.

Professor of Physiotherapy Mark Hancock and his research team have been investigating ways to shift the emphasis from treatment to prevention to improve the management of back pain, an approach that empowers individuals to manage their own health and reduces the cost to society and the healthcare system.

Far from the bed rest recommended for back pain in the past, current best practice includes the combination of exercise and education, both to treat current pain and to prevent future episodes.

While beneficial, some forms of exercise are not accessible or affordable to many people due to their high cost, complexity and need for supervision.

A simpler, more accessible method

The world-first WalkBack trial examined whether a programme of walking combined with education could be effective in preventing recurrences of low back pain.

The trial followed 701 adults who had recently recovered from an episode of low back pain, randomly allocating participants to either an individualised walking program facilitated by a physiotherapist and six education sessions across six months, or to a no-intervention control group.

The participants’ progress was then followed for between one and three years to collect information about any new recurrences of low back pain they experienced.

The researchers’ primary aim was to compare the two groups for the number of days before participants experienced a recurrence of back pain that impacted daily activities or required care from a healthcare provider.

They also evaluated the cost effectiveness of the intervention, including costs related to work absenteeism and healthcare services.

Longer pain-free periods

The paper’s senior author, Professor Hancock, says what they discovered could have a profound impact on how low back pain is managed.

“The intervention group had fewer occurrences of activity-limiting pain compared to the control group, and a longer average period before they had a recurrence, with a median of 208 days compared to 112 days,” Professor Hancock says. “The risk of having a recurrence that required seeking care was nearly halved in those in the intervention group.

“Walking is a low-cost, widely accessible and simple exercise that almost anyone can engage in, regardless of age, geographic location or socio-economic status.

“We don’t know exactly why walking is so good for preventing back pain, but it is likely to include the combination of gentle oscillatory movements, loading and strengthening the spinal structures and muscles, relaxation and stress relief, and the release of ‘feel-good’ endorphins.

“And of course, we also know that walking comes with many other health benefits, including cardiovascular health, improved bone density, maintenance of a healthy weight and improved mental health.”

Professor Hancock said the amount of walking each person completed was individualised based on a range of factors including their age, physical capacity, preferences and available time. Participants were given a rough guide to build up to 30 minutes, five times a week over a six-month period.

After three months, Professor Hancock said most of the people who took part were walking three to five days a week for an average of 130 minutes.

“You don’t need to be walking five or 10 kilometres every day to get these benefits,” Professor Hancock says.

A cost-effective option

The paper’s lead author, Postdoctoral Fellow Dr Natasha Pocovi, says in addition to providing participants with longer pain-free periods, they found the program was also cost effective.

“It not only improved people’s quality of life, but it reduced their need both to seek healthcare support and the amount of time taken off work by approximately half,” Dr Pocovi says.

“The exercise-based interventions to prevent back pain that have been explored previously are typically group-based and need close clinical supervision and expensive equipment, so they are much less accessible to the majority of patients.

“Our study has shown that this effective and accessible means of exercise has the potential to be successfully implemented on a much larger scale than other forms of exercise.”

To build on these findings, the team now hopes to explore how they can integrate the preventive approach into the routine care of patients who experience recurrent low back pain.

Source: MacQuarie University

Categories : Diseases, Syndromes and Conditions Pain ManagementTags :

In Knee Osteoarthritis, Inactivity may be more Complex than Believed

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Knee osteoarthritis (OA) is a common cause of pain and joint stiffness. And while physical activity is known to ease symptoms, only one in 10 people regularly exercise. Understanding what contributes to patients’ inactivity is the focus of a world first study from the University of South Australia. Here, researchers have found that people with knee OA unconsciously believe that activity may be dangerous to their condition, despite medical advice telling them otherwise.

The study, published in PAIN, found that of those surveyed, 69% of people with knee pain had stronger implicit (unconscious) beliefs that exercise was dangerous than the average person without pain. It’s an interesting finding that not only highlights the conflicted nature of pain and exercise, but also that what people say and what people think, deep down, may be entirely different things.

Lead researcher, and UniSA PhD candidate based at SAHMRI, Brian Pulling, says the research provides valuable insights for clinicians treating people with knee OA.

“Research shows that physical activity is good for people with knee OA, but most people with this condition do not move enough to support joint or general health,” Pulling says.

“To understand why people with OA might not be active, research studies typically use questionnaires to assess fear of moving. But unfortunately, questionnaires are limited – what we feel deep down (and how our system naturally reacts to something that is threatening) may be different to what we report. And we still know that many people are avoiding exercise, so we wanted to know why.”

To assess this, the researchers developed a tool that can detect and evaluate people’s implicit beliefs about exercise; that is, whether they unconsciously think activity is dangerous for their condition.

“We found that that even among those who said they were not fearful about exercise, they held unconscious beliefs that movement was dangerous,” Pulling says.

“Our research shows that people have complicated beliefs about exercise, and that they sometimes say one thing if asked directly yet hold a completely different implicit belief.

“People are not aware that what they say doesn’t match what they choose on the new task; they are not misrepresenting their beliefs.

“This research suggests that to fully understand how someone feels about an activity, we must go beyond just asking directly, because their implicit beliefs can sometimes be a better predictor of actual behaviour than what people report. That’s where our tool is useful.”

The online implicit association test presents a series of words and images to which a participant must quickly associate with being either safe or dangerous. The tool intentionally promotes instant responses to avoid deliberation and other influencing factors (such as responding how they think they should respond).

Associate Professor Tasha Stanton says that the new tool has the potential to identify a group of people who may have challenges increasing their activity levels and undertaking exercise.

“What people say and what people do are often two different things, Assoc Prof Stanton says.

“Having access to more accurate and insightful information will help health professionals better support their patients to engage with activity and exercise. It may also open opportunities for pain science education, exposure-based therapy, or cognitive functional therapy…things that would not usually be considered for someone who said that they were not scared to exercise.”

Researchers are now looking to see if implicit beliefs are directly associated with behaviour and are asking for people to complete the Implicit Association Test (takes seven minutes). At the end of the test participants are given their results in comparison to the rest of the population.

To take the test, please click here: https://unisasurveys.qualtrics.com/jfe/form/SV_0OZKUqzBNtiKGF0

Source: University of South Australia

Categories : Exercise Pain Management

With Gain, No Pain: Exercise Protects against Chronic Pain

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In 2023, researchers in Norway found that among more than 10 000 adults, those who were physically active had a higher pain tolerance than those who were sedentary; and the higher the activity level, the higher the pain tolerance.

After this finding, the researchers wanted to understand how physical activity could affect the chances of experiencing chronic pain several years later. And they wondered if this was related to how physical activity affects our ability to tolerate pain.

This prompted a new study from the researchers at UiT The Arctic University of Norway, the University Hospital of North Norway (UNN), and the Norwegian Institute of Public Health, which was published in the journal PAIN.

“We found that people who were more active in their free time had a lower chance of having various types of chronic pain 7-8 years later. For example, being just a little more active, such as going from light to moderate activity, was associated with a 5% lower risk of reporting some form of chronic pain later,” says doctoral fellow Anders Årnes at UiT and UNN and study author.

He adds that for severe chronic pain in several places in the body, higher activity was associated with a 16% reduced risk.

Measured cold pain tolerance

The researchers found that the ability to tolerate pain played a role in this apparent protective effect. That explains why being active could lower the risk of having severe chronic pain, whether or not it was widespread throughout the body.

“This suggests that physical activity increases our ability to tolerate pain and may be one of the ways in which activity helps to reduce the risk of severe chronic pain,” says Årnes.

The researchers included almost 7000 people in their study, recruited from the large Tromsø survey, which has collected data on people’s health and lifestyle over decades.

After obtaining information about the participants’ exercise habits during their free time, the researchers examined how well the same people handled cold pain in a laboratory. Later, they checked whether the participants experienced pain that lasted for three months or more, including pain that was located in several parts of the body or pain that was experienced as more severe.

Among the participants, 60% reported some form of chronic pain, but only 5% had severe pain in multiple parts of the body. Few people experienced more serious pain conditions.

Pain and exercise

When it comes to exercising if you already have chronic pain, the researcher says:

“Physical activity is not dangerous in the first place, but people with chronic pain can benefit greatly from having an exercise program adapted to help them balance their effort so that it is not too much or too little. Healthcare professionals experienced in treating chronic pain conditions can often help with this. A rule of thumb is that there should be no worsening that persists over an extended period of time, but that certain reactions in the time after training can be expected.”

Source: UiT The Arctic University of Norway

Categories : Neurology Pain ManagementTags :

Neuron Cluster may Create a Little-understood Form of Chronic Pain

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Stimulating a small cluster of neurons in the brain appears to create a response in mice that mimics nociplastic pain, a type of unexplained chronic pain, researchers at the University of Washington School of Medicine in Seattle have found. 

“When we stimulate these neurons, the mouse behaves as though gentle touch is very painful, which is one of the characteristics of nociplastic pain,” said Richard Palmiter, a professor of biochemistry and investigator of the Howard Hughes Medical Institute. Dr Logan Condon, who spearheaded this research as a PhD student at UW, was lead author on the paper, which was published in Cell Reports. 

Chronic pain can arise from ongoing injury or persistent damage to the nervous system. Pain caused by injury is called nociceptive from the Latin nocere “to harm.” Pain due to nerve damage is called neuropathic. But these categories do not explain a common form of chronic pain the persists even after an injury has fully healed and there is no evidence of neurological damage. This led the International Association for the Study of Pain to define a new category called nociplastic pain, meaning “able to be moulded.” 

Although the cause of nociplastic pain is unknown, scientists think it involves changes in pain circuits in the spinal cord and brain. These changes result in the perception of pain even when no nerve injury exists. 

In the new study, researchers demonstrated that stimulating a cluster of cells in the brain’s parabrachial nucleus can generate chronic pain behaviour typical of nociplastic pain. They also showed that inhibiting these cells can prevent pain from nerve injury. 

The parabrachial nucleus is in an area of the brain known as the pons. It acts as a hub that relays aversive sensory information from the body to different parts of the brain. The parabrachial neurons found to create nociplastic pain are called Calca neurons, named for a defining gene for these cells. 

“You can think of these Calca neurons as a warning system for the brain,” said Palmiter. “They respond to any aversive event you can think of – a pinch, a visual threat, a bad odour, a loud noise – and they tell your brain that something bad is happening in the environment and you’d better do something about it.”

It is possible to manipulate genetically defined neurons using viral techniques to express molecules that activate, or inhibit, those neurons. 

The researchers also found that the nociplastic pain behaviour continues even after the Calca-neuron activation has stopped. This suggests signals from the stimulated Calca neurons cause persistent effects – a sign of plasticity – in the nerve circuits leading to the spinal cord. 

They also showed that it was possible to create nociplastic behaviours in the mice by exposing them to unpleasant, aversive experiences like nausea, chemotherapy drugs or migraine-like conditions. 

Palmiter’s team is currently focusing on the neural circuits and plasticity that arises when parabrachial Calca neurons are activated.

“The brain is somehow sending signals to the spinal cord,” he said. “We want to figure out the pathway for those signals.”

Source: University of Washington

Categories : Gastrointestinal Pain ManagementTags :

Acid-lowering Meds Linked to Greater Risk of Migraines

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People who take acid-reducing drugs may have a higher risk of migraine and other severe headache than people who do not take these medications, a new study has shown. The acid-reducing drugs include proton pump inhibitors such as omeprazole and esomeprazole, histamine H2-receptor antagonists, or H2 blockers, such as cimetidine and famotidine, and antacid supplements.

The study, study published in Neurology®Clinical Practice, an official journal of the American Academy of Neurology, does not prove causation; only an association.

In acid reflux, stomach acid flows into the oesophagus, usually after a meal or when lying down, causing heartburn and ulcers. People with frequent acid reflux may develop gastroesophageal reflux disease, or GORD, which can lead to cancer of the oesophagus.

“Given the wide usage of acid-reducing drugs and these potential implications with migraine, these results warrant further investigation,” said study author Margaret Slavin, PhD, RDN, of the University of Maryland in College Park. “These drugs are often considered to be overprescribed, and new research has shown other risks tied to long-term use of proton pump inhibitors, such as an increased risk of dementia.”

For the study, researchers looked at data on 11,818 people who provided information on use of acid-reducing drugs and whether they had migraine or severe headache in the past three months.

A total of 25% of participants taking proton pump inhibitors had migraine or severe headache, compared to 19% of those who were not taking the drugs. A total of 25% of those taking H2 blockers had severe headache, compared to 20% of those who were not taking those drugs. And 22% of those taking antacid supplements had severe headache, compared to 20% of those not taking antacids.

When researchers adjusted for other factors that could affect the risk of migraine, such as age, sex and use of caffeine and alcohol, they found that people taking proton pump inhibitors were 70% more likely to have migraine than people not taking proton pump inhibitors. Those taking H2 blockers were 40% more likely and those taking antacid supplements were 30% more likely.

“It’s important to note that many people do need acid-reducing medications to manage acid reflux or other conditions, and people with migraine or severe headache who are taking these drugs or supplements should talk with their doctors about whether they should continue,” Slavin said.

Slavin noted that the study looked only at prescription drugs. Some of the drugs became available for over-the-counter use at non-prescription strength during the study period, but use of these over-the-counter drugs was not included in this study.

Other studies have shown that people with gastrointestinal conditions may be more likely to have migraine, but Slavin said that relationship is not likely to fully explain the tie between acid-reducing drugs and migraine found in the study.

A limitation of the study is that a small number of people were taking the drugs, especially the H2 blockers.

Source: American Academy of Neurology

Categories : Obstetrics & Gynaecology Pain ManagementTags :

A Third of Women Experience Migraines Associated with Menstruation

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Of the nearly 20 million women who participated in a U.S. national health survey, one-third reported migraines during menstruation. The analysis was conducted by researchers at Georgetown University Medical Center and Pfizer, Inc., which makes a migraine medication.

Because of the underuse of medications to help treat or prevent menstrual migraines, investigators wanted to understand how common menstrual migraines were and which groups of women could most benefit from potential therapies. The study, presented April 16, at the American Academy of Neurology 2024 Annual Meeting in Denver, also revealed the most common medications taken by those women seeking to prevent menstrual migraines.

“The first step in helping a woman with menstrual migraine is making a diagnosis; the second part is prescribing a treatment; and the third part is finding treatments patients are satisfied with and remain on to reduce disability and improve quality of life,” says the study author, Jessica Ailani, MD, professor of clinical neurology at Georgetown University School of Medicine.

The researchers used the 2021 U.S. National Health and Wellness Survey to analyse responses from women who reported their current migraine treatments, frequency and disabilities via the Migraine Disability Assessment Test (MIDAS), a five-question survey. A migraine headache can cause severe throbbing pain or a pulsing sensation, usually on one side of the head. It’s often accompanied by nausea, vomiting, and extreme sensitivity to light and sound.

“Discrepancies in the incidence of who gets migraine attacks associated with menses is likely due to premenopausal women having more regular menstrual cycles and thus more menstrual-related migraines,” says Ailani, also director of the MedStar Georgetown Headache Center at Medstar Georgetown University Hospital. “Additionally, as women move into their 40’s and become peri-menopausal, there tends to be a greater shift through the month in hormone levels also leading to frequent migraine attacks.”

The survey found that for all women during their menstrual periods, migraine attacks occurred as frequently as 4.5 times and that monthly only migraine headaches lasted 8.4 days, on average; 56.2 % of women had moderate-to-severe migraine-specific disabilities that ranked highest on the MIDAS scale.

When looking at treatments women in the survey used to help control their migraine symptoms, 42.4% used over-the-counter medications while 48.6% used prescription medications. Of the 63.9 % of women who used migraine treatments for acute symptoms, the most commonly used were triptans, a class of drugs developed in the 1990s to quiet overactive nerves associated with migraines and cluster headaches.

Sara’s story

Sara, a 38 year old mother of two, says her migraines are predictably and consistently worse during her period.

“It definitely disrupts my ability to go about my normal activities including at work,” Sara says. “I’m pretty lucky that I’m generally responsive to prescription medication, but I often still have to lie down for an hour or so while the medicine kicks in.”

Sara is being treated preventatively for migraines with Botox. She says over the past couple of months, she’s had a couple of migraines outside of when she gets her period, but that the headaches are definitely worse during menstruation.

“While I had my last period, I had a migraine every day for a week,” Sara says. “It’s starkly different [during menstruation].”

Prevention possibilities

Non-steroidal anti-inflammatory drugs (NSAIDs) are sometimes used as preventive medications for women with regular menstrual periods. In this study, 21.1% of women reported use of any migraine prevention medications or therapies.

“Preventive treatments are used less frequently than acute treatment for migraine,” Alaini said. “In my opinion, this is because preventive therapy is a long-term commitment by both a woman and her clinician to improving the disease process. Migraine is a life-long brain disease without a cure, and the goal of preventive therapy is to reduce disease burden and improve quality of life. Unfortunately, newer disease-specific treatments are costly, so generic older treatments are often used and come with greater side effects.”

Next steps

The researcher’s next steps involve looking at larger databases to see if they can mimic findings on a global scale. They want to determine if women with menstrual-related migraine are frequently turning to non-migraine treatments as was seen in around 53% of their current study group.

“As a headache specialist in the U.S., I know I can do better for women in my clinic, but what can be done for the millions of women who don’t get into a headache clinic? That is our true next step,” says Ailani. “If you have migraines related to your menstrual cycle, discuss this with your gynaecologist or neurologist. There are treatments that can help and if the first treatment tried does not work, do not give up.”

Source: Georgetown University Medical Center