Category: Pain Management

Categories : IT in Healthcare Pain ManagementTags :

Virtual Reality Nature Walks and “Magic” Hands: A New Era in Pain Management

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Photo by Matteo Vistocco on Unsplash

What if arthritis sufferers could take an immersive walk through a forest filled with soothing birdsong and then, with some help from hypnosis, come to experience their pain as separate from their body – and expel it?

That’s the goal of research led by David Ogez, a professor in the Department of Anesthesiology and Pain Medicine at Université de Montréal and a clinical researcher at the Maisonneuve-Rosemont Hospital Research Centre.

Together with postdoctoral researcher Valentyn Fournier, Ogez is testing an approach that combines medical hypnosis and virtual reality (VR) to help seniors manage chronic arthritis pain in the hands, a common and debilitating condition.

Their research was published online last month in BMJ Open.

“Chronic pain is a major public-health issue that affects about one in five people in Canada and as many as one in three over the age of 60,” said Ogez. “It significantly impacts quality of life, mobility and mental health.  But apart from pharmacological treatments, solutions are few.”

The problem lies in the limitations of drug treatments, including the risk of addiction to painkillers. This led Ogez and his team to explore complementary, non-invasive methods to help patients better manage their pain.

A powerful duo

Medical hypnosis is already recognized as an effective pain management tool, particularly in palliative care and post-operative settings. It relies on hypnotic suggestion—guided phrases that help patients alter their sensory and emotional perception of pain.

For example, patients may be asked to imagine submerging their sore hand in cold water, or be guided through controlled breathing techniques to synchronize their heartbeat and breathing to induce relaxation.

Ogez’s team wanted to take it one step further by combining the power of hypnosis with immersive virtual experiences.

Wearing a headset, the patient is transported to a Quebec landscape—a forest, mountains, a beach—accompanied by music and the sounds of nature. Developed in Quebec, this application was originally designed to give end-of-life patients the opportunity to “visit” places they never had the chance to see in real life.

Pairing hypnosis and VR makes it possible to visualize and manipulate pain, allowing patients to reclaim control of their bodies and their pain, research has shown.

One intervention being tested is the “magic hand.” In virtual reality, patients look at their hand and put little sparkles on the painful area to alleviate the pain. Another intervention involves guiding patients to “objectify” their pain: to make it visible on their hand and then remove it. 

“The pain is still there, but…”

The researchers are also interested in the physiological mechanisms responsible for the pain relief provided by these techniques, which may resemble those associated with mindfulness.

One hypothesis is that VR distracts the brain. By intensely engaging vision, hearing and concentration, VR redirects mental resources that would otherwise be mobilized by pain. Hypnosis then reinforces this diversion of attention by guiding the patient toward pleasant sensations and gradual relief.

Neuroscience research has shown that these techniques modulate the activity of the anterior cingulate cortex and primary somatosensory cortex, two brain regions involved in the emotional and perceptual processing of pain.

“The pain is still there, but its unpleasantness and intensity are reduced,” explained Ogez.

Exposure to nature also provides psychological benefits. “Nature refreshes attention, directing the mind away from negative stimuli and restoring our ability to focus on positive ones,” said Fournier.

Promising preliminary results

Beyond the immediate calming or distracting effects of a treatment session combining hypnosis and VR, the new research aims to help patients develop self-hypnosis skills they can use at home. 

The team is also working on developing a neurofeedback tool that patients can use to track and regulate their brain activity in real time in order to help them modulate their physiological responses during immersive VR experiences. 

While the study is presently in the randomized clinical trial phase, the preliminary feedback from participants is encouraging, said Ogez.

“We’re seeing good patient satisfaction, although we mustn’t confuse satisfaction with effectiveness,” he cautioned. “Still, we’re hopeful, since pain is partly a subjective experience.” 

Categories : Obstetrics & Gynaecology Pain ManagementTags :

New Study Challenges Fears About General Anaesthesia for C-sections

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Data analysed by Penn researchers clarifies risks associated with general anaesthesia, giving patients more control over their delivery experience.

Photo by Anna Shvets on Pexels

Regional anaesthesia has long been favoured for caesarean births due in part to concerns about the effects that general anaesthesia may have on newborns during labour and delivery. Powerful societal pressures also push the idea that mothers need to be awake during delivery to witness the first cry and capture the ‘perfect’ birth moment. But for some women who undergo a caesarean birth, the pain can become excruciating, even after they received a spinal or epidural block.

Now, new research from a team at the Perelman School of Medicine at the University of Pennsylvania, finds that general anaesthesia may be a reasonable alternative for many patients. The findings are published today in Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists.

“No patient should have to experience pain during caesarean section; as an anaesthesiologist, I never want someone to feel forced to choose between their baby’s health and not having to experience the pain of surgery,” said Mark Neuman, MD, MSc, Professor of Anesthesiology and senior author of the study. “Since regional anaesthesia is so widely used, it’s common for patients to feel that a spinal or epidural block is the only safe option for caesarean section. But as our study shows, anaesthesia type during pregnancy does not need to be one-size-fits-all.”

Reducing pain during C-section delivery

The research analysed 30 years’ worth of data from multiple clinical trials, comparing outcomes between general anaesthesia versus spinal or epidural anaesthesia for C-sections. The Penn study found that, while babies born under spinal or epidural anaesthesia had slightly higher Apgar scores than those born under general anaesthesia, the differences were small and not likely to be clinically meaningful.

While the majority of patients experience good outcomes with spinal or epidural block for caesarean delivery, recent studies show that up to one in six patients who receive an epidural or spinal may feel pain during their C-section. These experiences can be traumatic and have lasting emotional impacts.

The findings come amid growing public discourse on caesarean experiences. Recent podcasts and published news stories have featured candid patient accounts of pain under spinal or epidural anaesthesia. “This study equips women with evidence-based context about the use of general anaesthesia during c-section.” said Sarah Langer, MD, a resident in anaesthesiology at the Perelman School of Medicine and lead author the study. “Childbirth is a physically and emotionally demanding process, but we do not want patients to feel like there aren’t options when it comes to their anaesthesia for c-section,”

Broadening evidence-based choices

The study found that babies born under general anaesthesia were slightly more likely to need breathing support immediately after birth, but there was no increase in NICU admissions. The research does not suggest that general anaesthesia should replace regional techniques, but it can be a reasonable option in certain cases.

“For patients who are open to regional anaesthesia, spinal or epidural block remain great first choice options,” Neuman emphasised. “But having conversations with patients about general anaesthesia doesn’t need to be taboo. Patients deserve to know they have options, and our study helps provide the evidence to support those discussions.”

The authors note that most of the trials included in the analysis were conducted outside North America, highlighting the need for more US-based research in this area. They also point to historical barriers in studying women during pregnancy, which have limited the availability of robust data.

Source: Perelman School of Medicine at the University of Pennsylvania

Categories : Injury & Trauma Pain ManagementTags :

Peri-neuronal Injection of Botulinum Eases Pain in Ukrainian Amputees

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Botulinum injection around neuromas may also be effective for other forms of pain

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Botulinum toxin injections provided greater short-term relief for phantom limb pain than standard medical and surgical care among Ukrainian war amputees, reports a new study led by Northwestern Medicine and Ukrainian physicians.

The study, which involved 160 amputees treated at two hospitals in western Ukraine between 2022 and 2024, could ultimately benefit millions worldwide, according to the research team.

Post-amputation pain affects most amputees. The condition limits prosthetic use, mobility and quality of life. In the US, more than 2 million people live with limb loss. In Ukraine, it is estimated that over 100 000 soldiers and civilians have lost limbs since Russia’s full-scale invasion, which began in 2022.

“Botulinum toxin injected into painful stumps of residual limbs and around neuromas was on some outcome measures more effective than comprehensive medical and surgical treatment at one month post-treatment,” said senior study author Dr Steven P. Cohen, a professor of anaesthesiology and the vice chair of research and pain medicine at Northwestern University Feinberg School of Medicine.

Dr. Steven Cohen is a retired U.S. Army colonel who traveled to Ukraine to collaborate with local doctors.

“Our results show that botulinum toxin potentially could be a powerful short-term tool for treating post-amputation pain when used alongside comprehensive medical and surgical care,” said co-author Dr. Roman Smolynets, an anesthesiologist and intensive care specialist at Multidisciplinary Clinical Hospital of Emergency and Intensive Care in Lviv, Ukraine.

“It could be another step toward helping amputees live with less pain and more dignity. But always as an additional point to comprehensive medical and surgical care, not as a monotherapy.”

The study was published in the journal Archives of Physical Medicine and Rehabilitation.

Assessing pain before and after treatments

All study participants were amputees treated at the First Medical Union of Lviv or Ivano-Frankivsk Regional Hospital. About one-fifth received botulinum toxin injections around painful nerve endings, called neuromas, in addition to standard medical and physical therapy. The other participants received comprehensive medical and surgical treatment, which included surgical revision, nerve blocks, physical and psychological therapy, medications and other interventional procedures.

The research team assessed pain levels at the start of treatment and after one and three months, focusing separately on phantom limb pain (pain in the missing limb) and residual limb pain (pain at the stump site).

At one month, the botulinum toxin group experienced an average reduction of four points in phantom limb pain on a 10-point scale, compared with just one point among patients in the comparison group. Also at one month, 69% of patients who received botulinum toxin achieved a meaningful improvement (defined as at least a 30% drop in pain) in phantom limb pain, versus only 43% in the other patient group.

However, the results shifted at three months: Patients who received comprehensive care showed more durable pain relief than the botulinum toxin group, consistent with previous research showing that botulinum toxin’s pain-relieving effects typically last about three months.

A novel way to inject botulinum toxin

While botulinum toxin injections, a non-surgical treatment that alleviates pain by blocking nerve signals, are most commonly known for their use in cosmetic procedures, they are also an established tool to treat chronic pain.

In the study, the substance was injected in a novel way. The research team used ultrasound guidance to inject botulinum toxin directly around painful nerve endings and surrounding soft tissues, rather than into muscle or skin. This targeted “peri-neuromal” approach, the scientists believe, may explain the strong short-term reduction in pain by quieting nerve activity and local inflammation. Previous studies have shown botulinum toxin to be effective for neuropathic pain, but none injected it around painful nerves.

The new findings suggest that botulinum toxin injections near nerves may also help relieve other types of nerve pain, such as shingles-related pain, carpal tunnel syndrome and pain following surgeries like mastectomy or thoracotomy.

Friendship with a Ukrainian anaesthesiologist

Cohen, who traveled to Ukraine in 2024 to help launch the study, is a retired U.S. Army colonel who served four overseas tours in support of military operations; his son currently serves with the infantry.

In Ukraine, he partnered with Smolynets, who has treated thousands of soldiers and civilians injured in the war by working in the country’s largest trauma and emergency center, and Dr. Nadiya Segin, who is pioneering the use of Botulinum toxin and nerve stimulation to treat war injuries.

Smolynets will visit Chicago the week of Oct. 19 with a Ukrainian delegation for an observership program, spending time with Cohen at his pain medicine clinic and at a Shirley Ryan AbilityLab in downtown Chicago. The two physicians, now close friends, are available for interviews during that week.

More research in Ukraine

Cohen and his colleagues stress the need for larger, randomized trials to confirm their findings, refine patient selection and optimize botulinum toxin dosing. Future research should also explore whether repeat botulinum toxin injections over time could produce sustained benefits for post-amputation pain, as they appear to do for migraine treatment.

Cohen and Smolynets, who published another study in February about using hydrodissection for post-amputation pain in Ukraine, are also researching more novel war treatments in Ukraine, at Walter Reed, and Northwestern, for traumatic brain injury and PTSD. These studies are underway. 

“As a retired colonel and the father of an infantry soldier who could be deployed in future conflicts and suffered from traumatic brain injury while at the U.S. Military Academy, this research carries special personal meaning for me,” Cohen said.

Source: Northwestern University

Categories : Pain Management Substance UseTags :

Teens More Likely to Use Opioids when Parents Have Prescriptions

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Norwegian study of more than 21 000 young people found that those whose parents had persistent opioid prescriptions faced more than double the risk of persistent opioid use

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If a parent has persistent opioid prescriptions, their adolescent or young adult offspring has more than double the risk of persistent opioid use, according to a new study published October 23rd in the open-access journal PLOS Medicine by Anna Marcuzzi of the Norwegian University of Science and Technology, Norway, and colleagues.

The prescription of strong analgesics such as opioids is not recommended for young people. However, despite potential adverse long-term consequences, opioids are often prescribed for non-malignant pain in this population.

In the new study, researchers analysed data from 21 470 adolescents and young adults aged 13-29 years who participated in the population-based Young-HUNT or HUNT Study in Norway in 2006-2008 or 2017-2019. Each participant was linked with at least one parent who also participated in the HUNT study, and opioid prescription data were obtained from the Norwegian Prescription Database.

24.4% of young people had at least one opioid prescription during the seven-year follow-up period, while 1.3% had persistent opioid prescriptions, defined as prescriptions in at least three out of four quarters of a year. When a mother had persistent opioid prescriptions over a five-year period (two years before and three years after offspring participation), their offspring had 2.60 times the risk of persistent opioid use compared to those whose mothers had no prescriptions. When a father had persistent opioid prescriptions, their offspring had 2.37 times the risk of persistent opioid use. The association was also present but weaker for non-persistent opioid prescription – offspring whose mothers had two or more prescriptions had 1.34 times the risk of receiving any opioid prescription, while those whose fathers had two or more prescriptions had 1.19 times the risk, compared to offspring whose parents had no prescriptions. There was no clear evidence that parental chronic musculoskeletal pain status influenced these associations.

The authors note that because parental opioid prescriptions were measured both before and after offspring HUNT participation, some parental opioid prescriptions could have begun after offspring opioid use. However, they conclude that there is an association between parental and offspring opioid prescriptions.

“The study findings suggest that family-based strategies should be considered when managing pain conditions in adolescents and young adults to avoid potentially unnecessary opioid use,” they say.

The authors add, “Despite restrictive opioid policies, one in four adolescents and young adults received an opioid prescription during the seven years follow-up.”

“Adolescents whose parents had two or more opioid prescriptions had a more than two-fold higher risk of persistent opioid use (ie, multiple prescriptions in a year) than if the parents had no opioid prescriptions.”

Provided by PLOS

Categories : Cancer Pain ManagementTags :

Are Cancer Surgery Patients at Risk of Persistent Opioid Use?

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Study reveals that 1 in 10 will initiate opioid prescriptions long term.

Photo by Anna Shvets on Pexels

New research indicates that many patients who undergo surgery with the intent to cure early-stage cancer continue or start opioid prescriptions in the year following surgery. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

Pain management is essential during cancer care, but prescription opioid practices associated with cancer treatment may lead to unsafe long-term opioid use and adverse outcomes such as opioid use disorder and opioid overdose. To assess the situation, investigators examined rates of new persistent opioid use in the year following surgery for stage 0 to 3 cancers among 9213 U.S. Veterans who were opioid-naïve (not on prescribed opioids the year prior to their cancer diagnosis).

The team found that potentially dangerous co-prescription of opioid and benzodiazepine (a central nervous system depressant that treats anxiety, insomnia, and seizures and should not be combined with opioids) medications occurred in 366 (4.0%) Veterans during follow-up. Persistent opioid use occurred in 981 (10.6%). A higher intensity of exposure to opioid prescriptions during treatment was associated with these outcomes. People with a prior history of chronic pain, greater comorbidities, lower socioeconomic status, and who received adjuvant chemotherapy were at especially high risk of opioid use in the year after surgery.

“Minimising opioid exposure associated with cancer treatment while providing effective pain control will decrease long-term health risks among cancer survivors,” said lead author Marilyn M. Schapira, MD, MPH, of the University of Pennsylvania. “This is important as many patients are living longer after a cancer diagnosis and treatment.”

Source:

Categories : Antibiotics Pain ManagementTags :

Paracetamol and Ibuprofen Linked to Antibiotic Resistance

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Study evaluated nine common medications used in old age care homes

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New research from the University of South Australia shows that the trusted staples of paracetamol and ibuprofen are quietly fuelling one of the world’s biggest health threats: antibiotic resistance.

In the first study of its kind, researchers found that ibuprofen and paracetamol are not only driving antibiotic resistance when used individually but amplifying it when used together.

Assessing the interaction of non-antibiotic medications, the broad-spectrum antibiotic ciprofloxacin, and Escherichia coli, researchers found that ibuprofen and paracetamol significantly increased bacterial mutations, making E. coli highly resistant to the antibiotic.

It’s an important finding that has serious health implications, particularly for people in aged care homes, where multiple medications are regularly administered.

The World Health Organization reports that antimicrobial resistance is a global threat to public health, and that bacterial resistance was directly responsible for 1.27 million global deaths in 2019.

Lead researcher UniSA’s Associate Professor Rietie Venter says the findings raise important questions about the risks of polypharmacy in aged care.

“Antibiotics have long been vital in treating infectious diseases, but their widespread overuse and misuse have driven a global rise in antibiotic-resistant bacteria,” Assoc Prof Venter says.

“This is especially prevalent in residential aged care facilities, where older people are more likely to be prescribed multiple medications – not just antibiotics, but also drugs for pain, sleep, or blood pressure – making it an ideal breeding ground for gut bacteria to become resistant to antibiotics.

“In this study we looked at the effect of non-antibiotic medicines and ciprofloxacin, an antibiotic which is used to treat common skin, gut or urinary tract infections.

“When bacteria were exposed to ciprofloxacin alongside ibuprofen and paracetamol, they developed more genetic mutations than with the antibiotic alone, helping them grow faster and become highly resistant. Worryingly, the bacteria were not only resistant to the antibiotic ciprofloxacin, but increased resistance was also observed to multiple other antibiotics from different classes.

“We also uncovered the genetic mechanisms behind this resistance, with ibuprofen and paracetamol both activating the bacteria’s defences to expel antibiotics and render them less effective.”

The study assessed nine medications* commonly used in residential aged care: ibuprofen, diclofenac, paracetamol, furosemide, metformin, atorvastatin, tramadol, temazepam, and pseudoephedrine.

Assoc Prof Venter says the study shows how antibiotic resistance is a more complex challenge than previously understood, with common non-antibiotic medications also playing a role.

“Antibiotic resistance isn’t just about antibiotics anymore,” Assoc Prof Venter says.

“This study is a clear reminder that we need to carefully consider the risks of using multiple medications – particularly in aged care where residents are often prescribed a mix of long-term treatments.

“This doesn’t mean we should stop using these medications, but we do need to be more mindful about how they interact with antibiotics – and that includes looking beyond just two-drug combinations.”

The researchers are calling for further studies into drug interactions among anyone on long-term medication treatment regimes so we can gain a greater awareness of how common medications may impact antibiotic effectiveness.

Source: University of South Australia

Categories : Pain ManagementTags :

Off-label Use of Ketamine for Chronic Pain is Unsupported by Evidence

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Results show no clear evidence of benefit for ketamine in chronic pain and identified an increased risk of adverse effects such as delusions, delirium, paranoia, nausea, and vomiting

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The off-label use of ketamine to treat chronic pain is not supported by scientific evidence, a new Cochrane review has found.

Ketamine is an anaesthetic commonly used for procedural sedation and short-term pain relief. Ketamine is also frequently prescribed off-label to manage chronic pain conditions such as nerve pain, fibromyalgia and complex regional pain syndrome. It is one of several NMDA receptor antagonists – a group of drugs thought to reduce pain by blocking certain brain receptors involved in pain signalling.

The review, conducted by researchers from UNSW Sydney, Neuroscience Research Australia (NeuRA), and Brunel University of London, examined 67 trials involving over 2300 adult participants. It assessed five NMDA receptor antagonists: ketamine, memantine, dextromethorphan, amantadine, and magnesium.

Results show no clear evidence of benefit for ketamine in chronic pain and identified an increased risk of adverse effects such as delusions, delirium, paranoia, nausea, and vomiting. Evidence was rated low to very low certainty, due to small study sizes and poor methodological quality.

“We want to be clear – we’re not saying ketamine is ineffective, but there’s a lot of uncertainty,” said Michael Ferraro, Doctoral Candidate at UNSW and NeuRA, first author of the review. “The data could point to a benefit or no effect at all. Right now, we just don’t know.”

Researchers looked at the effects across various chronic pain conditions and dosing strategies but found no clear evidence of benefit in any specific condition or dose. Side effects were a major concern, particularly with intravenous use.

“The most common adverse events we saw were psychotomimetic effects such as delusions, delirium and paranoia, as well as nausea and vomiting.” said Ferraro. “These effects are distressing for many patients. Clinicians often try to balance the dose for pain relief without triggering those symptoms, but this isn’t always achieved.”

The review also found no studies that reported on two key outcomes: whether ketamine reduced depressive symptoms or opioid use. This is notable, as ketamine is often proposed for patients with depressive symptoms or opioid tolerance.

“This group of drugs, and ketamine in particular, are in relatively common use for chronic pain around the world. Yet we have no convincing evidence that they are delivering meaningful benefits for people with pain, even in the short term,” said Neil O’Connell, Professor at Brunel University of London, co-senior author of the review. “That seems a good reason to be cautious in the clinic and clearly indicates an urgent need to undertake high quality trials.”

The authors hope the review will help inform patients and clinicians weighing up potential benefits and harms, and guide future research. While more evidence is needed, this review highlights the importance of high-quality trials to understand whether ketamine has a role in chronic pain care.

“We’ve seen the harm that can come from taking medicines developed for acute pain and applying them to chronic pain, opioids are a prime example. Now we’re seeing a similar pattern with ketamine,” said co-senior author James McAuley, Professor at UNSW and senior researcher at NeuRA . “As opioid prescribing is slowly reduced, there’s a growing demand for alternatives, but we need to be careful not to rush into widespread use without strong evidence.”

Source: Cochrane

Categories : Neurology Pain ManagementTags :

From Injury to Agony: The Brain Pathway that Turns Pain into Suffering

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Salk scientists uncover a key neural circuit in mice that gives pain its emotional punch, opening new doors for treating fibromyalgia, migraine, and PTSD


CGRP-expressing neurons (green) in the parvocellular subparafascicular nucleus (SPFp) of the thalamus.
Credit: Salk Institute

More than just a physical sensation, pain also carries emotional weight. That distress, anguish, and anxiety can turn a fleeting injury into long-term suffering.

Salk Institute researchers have now identified a brain circuit that gives physical pain its emotional tone, revealing a new potential target for treating chronic and affective pain conditions such as fibromyalgia, migraine, and post-traumatic stress disorder (PTSD).

Published in PNAS, the study identifies a group of neurons in a central brain area called the thalamus that appears to mediate the emotional or affective side of pain in mice. This new pathway challenges the textbook understanding of how pain is processed in the brain and body.

“For decades, the prevailing view was that the brain processes sensory and emotional aspects of pain through separate pathways,” says senior author Sung Han, associate professor and holder of the Pioneer Fund Developmental Chair at Salk. “But there’s been debate about whether the sensory pain pathway might also contribute to the emotional side of pain. Our study provides strong evidence that a branch of the sensory pain pathway directly mediates the affective experience of pain.”

The physical sensation of pain allows immediate detection, assessment of its intensity, and identification of its source. The affective part of pain is what makes it so unpleasant – the emotional discomfort motivates avoidance.

This is a critical distinction. Most people start to perceive pain at the same stimulus intensities, meaning the sensory side of pain is processed similarly. But the ability to tolerate pain varies greatly. The degree of suffering or feeling threatened by pain is determined by affective processing, and if that becomes too sensitive or lasts too long, it can result in a pain disorder. This makes it important to understand which parts of the brain control these different dimensions of pain.

Sensory pain was thought to be mediated by the spinothalamic tract, a pathway that sends pain signals from the spinal cord to the thalamus, which then relays them to sensory processing areas across the brain.

Affective pain was generally thought to be mediated by a second pathway called the spinoparabrachial tract, which sends pain information from the spinal cord into the brainstem.

However, previous studies using older research methods have suggested the circuitry of pain may be more complex. This long-standing debate inspired Han and his team to revisit the question with modern research tools.

Using advanced techniques to manipulate the activity of specific brain cells, the researchers discovered a new spinothalamic pathway in mice. In this circuit, pain signals are sent from the spinal cord into a different part of the thalamus, which has connections to the amygdala, the brain’s emotional processing center. This particular group of neurons in the thalamus can be identified by their expression of CGRP (calcitonin gene-related peptide), a neuropeptide originally discovered in Professor Ronald Evans’ lab at Salk.

When the researchers “turned off” (genetically silenced) these CGRP neurons, the mice still reacted to mild pain stimuli, such as heat or pressure, indicating their sensory processing was intact. However, they didn’t seem to associate lasting negative feelings with these situations, failing to show any learned fear or avoidance behaviors in future trials. On the other hand, when these same neurons were “turned on” (optogenetically activated), the mice showed clear signs of distress and learned to avoid that area, even when no pain stimuli had been used.

“Pain processing is not just about nerves detecting pain; it’s about the brain deciding how much that pain matters,” says first author Sukjae Kang, a senior research associate in Han’s lab. “Understanding the biology behind these two distinct processes will help us find treatments for the kinds of pain that don’t respond to traditional drugs.”

Many chronic pain conditions—such as fibromyalgia and migraine—involve long, intense, unpleasant experiences of pain, often without a clear physical source or injury. Some patients also report extreme sensitivity to ordinary stimuli like light, sound, or touch, which others would not perceive as painful.

Han says overactivation of the CGRP spinothalamic pathway may contribute to these conditions by making the brain misinterpret or overreact to sensory inputs. In fact, transcriptomic analysis of the CGRP neurons showed that they express many of the genes associated with migraine and other pain disorders.

Notably, several CGRP blockers are already being used to treat migraines. This study may help explain why these medications work and could inspire new nonaddictive treatments for affective pain disorders.

Han also sees potential relevance for psychiatric conditions that involve heightened threat perception, such as PTSD. Growing evidence from his lab suggests that the CGRP affective pain pathway acts as part of the brain’s broader alarm system, detecting and responding to not only pain but a wide range of unpleasant sensations. Quieting this pathway with CGRP blockers could offer a new approach to easing fear, avoidance, and hypervigilance in trauma-related disorders.

Importantly, the relationship between the CGRP pathway and the psychological pain associated with social experiences like grief, loneliness, and heartbreak remains unclear and requires further study.

“Our discovery of the CGRP affective pain pathway gives us a molecular and circuit-level explanation for the difference between detecting physical pain and suffering from it,” says Han. “We’re excited to continue exploring this pathway and enabling future therapies that can reduce this suffering.”

Source: Salk Institute

Categories : Pain ManagementTags :

Podcast: Paracetamol’s Newly Discovered Mechanism Could Unlock Powerful New Analgesics

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Credit: Pixabay CC0

Despite being used for decades as a pain reliever, paracetamol’s mechanism of action was never fully known. Now, new research from the University of Jerusalem points to an unexpected effect, one which may usher in a whole new era of analgesics.

In QuickNews’ first podcast, you can listen to a discussion on how a newly discovered mechanism of action for paracetamol helps it achieve its analgesic effect, and how this could be applied to the development of novel, highly specific pain relievers.

Categories : Neurology Pain ManagementTags :

GLP-1 Therapy Reduces Brain Pressure and Migraine Frequency

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A diabetes medication that lowers brain fluid pressure has cut monthly migraine days by more than half, according to a new study presented at the European Academy of Neurology (EAN) Congress 2025

Photo by Kindel Media

A diabetes medication that lowers brain fluid pressure has cut monthly migraine days by more than half, according to a new study presented at the European Academy of Neurology (EAN) Congress 2025.1

Researchers at the Headache Centre of the University of Naples “Federico II” gave the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide to 26 adults with obesity and chronic migraine (defined as ≥ 15 headache days per month). Patients reported an average of 11 fewer headache days per month, while disability scores on the Migraine Disability Assessment Test dropped by 35 points, indicating a clinically meaningful improvement in work, study, and social functioning.

GLP-1 agonists have gained recent widespread attention, reshaping treatment approaches for several diseases, including diabetes and cardiovascular disease.2 In the treatment of type 2 diabetes, liraglutide helps lower blood sugar levels and reduce body weight by suppressing appetite and reducing energy intake.3,4,5

Importantly, while participants’ body-mass index declined slightly (from 34.01 to 33.65), this change was not statistically significant. An analysis of covariance confirmed that BMI reduction had no effect on headache frequency, strengthening the hypothesis that pressure modulation, not weight loss, drives the benefit.

“Most patients felt better within the first two weeks and reported quality of life improved significantly”, said lead researcher Dr Simone Braca. “The benefit lasted for the full three-month observation period, even though weight loss was modest and statistically non-significant.”

Patients were screened to exclude papilledema (optic disc swelling resulting from increased intracranial pressure) and sixth nerve palsy, ruling out idiopathic intracranial hypertension (IIH) as a confounding factor. Growing evidence closely links subtle increases in intracranial pressure to migraine attacks.6 GLP-1-receptor agonists such as liraglutide reduce cerebrospinal fluid secretion and have already proved effective in treating IIH.7 Therefore, building on these observations, Dr Braca and colleagues hypothesised that exploiting the same mechanism of action might ultimately dampen cortical and trigeminal sensitisation that underlie migraine.

“We think that, by modulating cerebrospinal fluid pressure and reducing intracranial venous sinuses compression, these drugs produce a decrease in the release of calcitonin gene-related peptide (CGRP), a key migraine-promoting peptide”, Dr Braca explained. “That would pose intracranial pressure control as a brand-new, pharmacologically targetable pathway.”

Mild gastrointestinal side effects (mainly nausea and constipation) occurred in 38% of participants but did not lead to treatment discontinuation.

Following this exploratory 12-week pilot study, a randomised, double-blind trial with direct or indirect intracranial pressure measurement is now being planned by the same research team in Naples, led by professor Roberto De Simone. “We also want to determine whether other GLP-1 drugs can deliver the same relief, possibly with even fewer gastrointestinal side effects”, Dr Braca noted.

If confirmed, GLP-1-receptor agonists could offer a new treatment option for the estimated one in seven people worldwide who live with migraine,8 particularly those who do not respond to current preventives. Given liraglutide’s established use in type 2 diabetes and obesity, it may represent a promising case of drug repurposing in neurology.

References

  1. Braca S., Russo C. et al. GLP-1R Agonists for the Treatment of Migraine: A Pilot Prospective Observational Study. Abstract A-25-13975. Presented at the 11th EAN Congress (Helsinki, Finland).
  2. Zheng, Z., Zong, Y., Ma, Y. et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Sig Transduct Target Ther 9, 234 (2024).
  3. Lin, C. H. et al. An evaluation of liraglutide including its efficacy and safety for the treatment of obesity. Expert Opin. Pharmacother. 21, 275–285 (2020).
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Source: EurekAlert!