Category: Pain Management

Categories : Genetics Pain ManagementTags :

The Molecular Secrets of the ‘Feel No Pain’ Gene

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The biology underpinning a rare genetic mutation that allows its carrier to feel almost no pain, heal faster and had reduced anxiety and fear, has been uncovered in a new study published in Brain.

Though it may sound like the stuff of superheroes, the carrier of the genetic mutation is an ordinary Scottish woman named Jo Cameron, who was first referred to pain geneticists at University College London in 2013, after her doctor noticed that she experienced no pain after major surgeries on her hip and hand. In 2019, they identified a new gene that they appropriately named FAAH-OUT, which had a rare genetic mutation. In combination with another, more common mutation in FAAH, it was found to be the cause of Jo’s unique characteristics.

The new research describes how the mutation in FAAH-OUT ‘turns down’ FAAH gene expression, as well as the knock-on effects on other molecular pathways linked to wound healing and mood. It is hoped the findings will lead to new drug targets and open up new avenues of research in these areas.

The area of the genome containing FAAH-OUT had previously been assumed to be ‘junk’ DNA that had no function, but it was found to mediate the expression of FAAH, a gene that is part of the endocannabinoid system and that is well-known for its involvement in pain, mood and memory.

In this study, the team from UCL sought to understand how FAAH-OUT works at a molecular level, the first step towards being able to take advantage of this unique biology for applications like drug discovery.

This included a range of approaches, such as CRISPR-Cas9 experiments on cell lines to mimic the effect of the mutation on other genes, as well as analysing the expression of genes to see which were active in molecular pathways involved with pain, mood and healing.

The team observed that FAAH-OUT regulates the expression of FAAH. When it is significantly turned down as a result of the mutation carried by Jo Cameron, FAAHenzyme activity levels are significantly reduced.

Dr Andrei Okorokov (UCL Medicine), a senior author of the study, said: “The FAAH-OUT gene is just one small corner of a vast continent, which this study has begun to map. As well as the molecular basis for painlessness, these explorations have identified molecular pathways affecting wound healing and mood, all influenced by the FAAH-OUT mutation. As scientists it is our duty to explore and I think these findings will have important implications for areas of research such as wound healing, depression and more.”

The authors looked at fibroblasts taken from patients to study the effects of the FAAH-OUT-FAAH axis on other molecular pathways. While the mutations that Jo Cameron carries turn down FAAH, they also found a further 797 genes that were turned up and 348 that were turned down. This included alterations to the WNT pathway that is associated with wound healing, with increased activity in the WNT16 gene that has been previously linked to bone regeneration.

Two other key genes that were altered were BDNF, which has previously been linked to mood regulation and ACKR3, which helps to regulate opioid levels. These gene changes may contribute to Jo Cameron’s low anxiety, fear and painlessness.

Senior study author Professor James Cox said: “The initial discovery of the genetic root of Jo Cameron’s unique phenotype was a eureka moment and hugely exciting, but these current findings are where things really start to get interesting. By understanding precisely what is happening at a molecular level, we can start to understand the biology involved and that opens up possibilities for drug discovery that could one day have far-reaching positive impacts for patients.”

Source: University College London

Categories : Pain ManagementTags :

Evidence is Lacking for Most Antidepressants Prescribed for Chronic Pain

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Most antidepressants used for chronic pain are being prescribed with “insufficient” evidence of their effectiveness, scientists have warned. A major investigation into medications used to manage long-term pain found that harms of many of the commonly recommended drugs have not been well studied.

In a Cochrane review, scientists examined 176 trials consisting of nearly 30 000 patients involved in assessments which prescribed antidepressants for chronic pain.

Among the drugs studied were amitriptyline, fluoxetine, citalopram, paroxetine, sertraline, and duloxetine – with only the latter showing reliable evidence for pain relief. One third of people globally are living with chronic pain, World Health Organization data shows, with many prescribed antidepressants for relieving symptoms.

Lead author Professor Tamar Pincus from the University of Southampton said: “This is a global public health concern. Chronic pain is a problem for millions who are prescribed antidepressants without sufficient scientific proof they help, nor an understanding of the long-term impact on health.

“Our review found no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for their safety for chronic pain at any point. Though we did find that duloxetine provided short-term pain relief for patients we studied, we remain concerned about its possible long-term harm due to the gaps in current evidence.”

Amitriptyline is one of the most commonly prescribed antidepressants for pain management worldwide. In the last 12 months, around 10 million prescriptions were given to patients in England at the 10mg dose recommended for pain. By comparison, five million prescriptions were given at the higher doses recommended for depression.

For duloxetine, three and a half million prescriptions were dispensed in England, but the recommended doses do not currently differ between conditions.

The two-year Cochrane study was the largest ever assessment of antidepressants recommended by leading bodies including the UK’s National Institute for Health and Care Excellence (NICE) and the Food and Drug Administration (FDA) in the USA.

Statistician Gavin Stewart, review co-author from Newcastle University, said: “We are calling on governing health bodies NICE and the FDA to update their guidelines to reflect the new scientific evidence, and on funders to stop supporting small and flawed trials. Evidence synthesis is often complex and nuanced but the evidence underpinning the use of these treatments is not equivalent, so current treatment modalities are hard to justify.”

The review revealed that duloxetine was consistently the highest-rated medication and was equally as effective for fibromyalgia, musculoskeletal, and neuropathic pain conditions.

Other results showed:

  • Standard doses of duloxetine are as successful for reducing pain as higher quantities,
  • Milnacipran was also effective at reducing pain, but scientists are not as confident as duloxetine due to fewer studies with fewer people.

Prof Tamar Pincus added: “We simply cannot tell about other antidepressants because sufficiently good studies are not available – but it does not mean that people should stop taking prescribed medication without consulting their GP.”

Scientists responsible for the review, funded by the NIHR’s Health Technology Assessment programme, were from the universities of Southampton, Newcastle, Bristol, UCL, Bath, and Keele, alongside Oxford University Hospital.

The team assessed the trials using a statistical method that enables researchers to combine data from relevant studies to estimate the effects of different drugs, which have not been compared directly in individual trials.

University of Southampton researcher Dr Hollie Birkinshaw said: “Though previous investigations show that some antidepressants might relieve pain, there has never been a comprehensive study examining all medications across all chronic conditions – until now.

“The only reliable evidence is for duloxetine. Adopting a person-centred approach is critical to treatment, and when patients and clinicians decide together to try antidepressants they should start from the drug for which there is good evidence.”

Source: University of Southampton

Categories : Pain ManagementTags :

Avoiding Addiction and Hallucination in the Quest for New Anaesthetics

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Photo by Louis Reed on Unsplash

Strategies to treat pain without triggering dangerous side effects such as euphoria and addiction have proven elusive. For decades, scientists have attempted to develop drugs that selectively activate one type of opioid receptor to treat pain while not activating another type of opioid receptor linked to addiction. Unfortunately, those compounds can cause a different unwanted effect: hallucinations. But a new study published in the journal Nature has identified a potential route to pain relief that neither triggers addiction nor activates the pathway that causes hallucinations.

Painkilling drugs such as morphine and oxycodone, as well as illegal street drugs such as heroin and fentanyl, activate what are known as mu opioid receptors on nerve cells. Those receptors relieve pain but also cause euphoria, contributing to addiction. An alternative strategy is to target another opioid receptor, called the kappa opioid receptor. Scientists attempting to make drugs that target only the kappa receptor have found that they also effectively relieve pain, but they can be associated with other side effects such as hallucinations.

Research led by Washington University School of Medicine in St. Louis has identified the potential mechanisms behind such hallucinations, with the goal of developing painkillers without this side effect. Using electron microscopes, the researchers identified the way that a natural compound related to the salvia plant selectively binds only to the kappa receptor but then causes hallucinations.

“Since 2002, scientists have been trying to learn how this small molecule causes hallucinations through kappa receptors,” said principal investigator Tao Che, PhD, an assistant professor of anesthesiology. “We determined how it binds to the receptor and activates potential hallucinogenic pathways, but we also found that other binding sites on the kappa receptor don’t lead to hallucinations.”

Developing new drugs to target these other kappa receptor binding sites may relieve pain without either the addictive problems associated with older opioids or the hallucinations associated with the existing drugs that selectively target the kappa opioid receptor.

Targeting the kappa receptor to block pain without hallucinations would be an important step forward, according to Che, because opioid drugs that interact with the mu opioid receptor have led to the current opioid epidemic, causing more than 100 000 overdose deaths in the US in 2021.

“Opioids, especially synthetic opioids such as fentanyl, have contributed to far too many overdose deaths,” Che said. “There’s no doubt we need safer pain-relieving drugs.”

Che’s team, led by first author Jianming Han, PhD, a postdoctoral research associate in Che’s laboratory, found that a class of signaling proteins called G proteins cause the kappa opioid receptor to activate several different pathways.

“There are seven G proteins linked to the kappa receptor, and although they are very similar to each other, the differences between the proteins may help explain why some compounds can cause side effects such as hallucinations,” Han said. “By learning how each of the proteins binds to the kappa receptor, we expect to find ways to activate that receptor without causing hallucinations.”

The function of the G proteins has largely been unclear until now, particularly the protein that activates the pathway lined to hallucinations.

“All of these proteins are similar to one another, but the specific protein subtypes that bind to the kappa receptor determine which pathways will be activated,” Che said. “We have found that the hallucinogenic drugs can preferentially activate one specific G protein but not other, related G proteins, suggesting that beneficial effects such as pain relief can be separated from side effects such as hallucinations. So we expect it will be possible to find therapeutics that activate the kappa receptor to kill pain without also activating the specific pathway that causes hallucinations.”

Source: Washington University School of Medicine

Categories : Cardiovascular Disease Pain ManagementTags :

Researchers Quantify Risk Factors for Oral Diclofenac

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Safety concerns related to the widely used analgesic diclofenac may be tied to a little-studied drug-metabolising enzyme which can vary as much as 3000 times across individuals, according to new research published in the journal Clinical Pharmacology & Therapeutics.

The findings could be used to develop ways to identify those at risk of serious side effects from the drug. They may help determine safer dosing standards for specific populations, including women, young children and people of certain ethnicities.

Used to treat arthritis-associated pain and inflammation, diclofenac was available over-the-counter in the US until 2013, when the Food and Drug Administration restricted it to prescription-only use following reports of the drug causing heart damage. More than 10 million prescriptions per year are written for it in the US. It is also one of the most widely used non-steroidal anti-inflammatory drugs worldwide, and is still over-the-counter in many countries. 

“Most patients who are using diclofenac have arthritis, and many of them are at risk of heart disease,” senior author Bhagwat Prasad, an associate professor at Washington State University. “So there is a concern that taking diclofenac may be putting them at even greater risk of cardiovascular events such as heart attack and stroke.”

Previous findings by the WSU team had found a high degree of variability in the expression of UGT2B17, an enzyme that is a known player in diclofenac metabolism. They found that the enzyme is present at much lower levels in women than in men, which could explain the increased risk of heart damage seen in women taking diclofenac. The enzyme was also mostly absent in children under age 9 and discovered large ethnicity-based differences in the number of people who lack the gene for the enzyme altogether, which ranges from around 20% of Caucasians up to around 90% of Japanese people.

In this new study, the WSU researchers used human liver and intestinal samples along with computer modelling to quantify the degree to which this enzyme contributes to diclofenac metabolism relative to other related enzymes. They found it to be a major player, supporting the idea that low levels of the UGT2B17 enzyme may be the cause of heart damage tied to diclofenac use.

“No one knew why this heart toxicity is happening in some individuals,” said first author Deepak Ahire, a graduate student in the WSU College of Pharmacy and Pharmaceutical Sciences. “Our study showed, for the first time, that UGT2B17 is important in diclofenac metabolism and suggests that differences in UGT2B17 expression are what makes people’s response to diclofenac so variable, leading to toxicity in some whereas for others the drug simply does not work.”

Ahire said that their study found that this enzyme metabolises diclofenac mainly in the intestine, unlike other related enzymes that are active mostly in the liver. Thus the observed effects are limited to diclofenac tablets taken by mouth, which provides for the quickest absorption and pain relief.

The findings suggest genetic testing could help healthcare providers evaluate safety risks before prescribing diclofenac. Prasad also noted that drug regulatory authorities in countries where diclofenac is still available over the counter should consider doing efficacy testing to determine the optimal dose of the drug for their local market.

The WSU researchers are currently in the process of confirming their findings in a pilot clinical trial. Their next step would be to pursue collaborations with large hospitals to study the connection between diclofenac and heart damage in patients’ electronic medical records.

Source: Washington State University

Categories : Pain ManagementTags :

Scientists Probe Links Between Chronic Alcohol Use and Pain Sensitivity

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The links between alcohol and pain are complex. Research published in the British Journal of Pharmacology suggests that chronic alcohol consumption may increase drinkers’ pain sensitivity through two different molecular mechanisms – the first driven by alcohol intake and the second by alcohol withdrawal.

The research also suggests potential new drug targets for treating alcohol-associated chronic pain and hypersensitivity.

“There is an urgent need to better understand the two-way street between chronic pain and alcohol dependence,” says senior author Marisa Roberto, PhD, the Schimmel Family Chair of Molecular Medicine, and a professor of neuroscience at Scripps Research. “Pain is both a widespread symptom in patients suffering from alcohol dependence, as well as a reason why people are driven to drink again.”

Over time, alcohol use disorder (AUD) can trigger the development of numerous chronic diseases, including heart disease, stroke, liver disease and some cancers. Among the many impacts of long-term alcohol consumption is pain: more than half of people with AUD experience persistent pain of some type. This includes alcoholic neuropathy, which is nerve damage that causes chronic pain and other symptoms.

Studies have also found that AUD is associated with changes in how the brain processes pain signals, as well as changes to how immune system activation occurs. In turn, this pain can lead to increased alcohol consumption. Moreover, during withdrawal, people with AUD can experience allodynia, in which a harmless stimulus is perceived as painful.

Roberto and her colleagues were interested in learning the underlying causes of these different types of alcohol-related pain. In the new study, they compared three groups of adult mice: animals that were dependent on alcohol (excessive drinkers), animals that had limited access to alcohol and were not considered dependent (moderate drinkers), and those that had never been given alcohol.

In dependent mice, allodynia developed during alcohol withdrawal, and subsequent alcohol access significantly decreased pain sensitivity. Separately, about half of the mice that were not dependent on alcohol also showed signs of increased pain sensitivity during alcohol withdrawal but, unlike the dependent mice, this neuropathy was not reversed by re-exposure to alcohol.

When Roberto’s group then measured levels of inflammatory proteins in the animals, they discovered that while inflammation pathways were elevated in both dependent and non-dependent animals, specific molecules were only increased in dependent mice. This indicates that different molecular mechanisms may drive the two types of pain. It also suggests which inflammatory proteins may be useful as drug targets to combat alcohol-related pain.

“These two types of pain vary greatly, which is why it is important to be able to distinguish between them and develop different ways to treat each type,” says first author Vittoria Borgonetti, PhD, a postdoctoral associate at Scripps Research.

Roberto’s group is continuing studies on how these molecules might be used to diagnose or treat alcohol-related chronic pain conditions.

“Our goal is to unveil new potential molecular targets that can be used to distinguish these types of pain and potentially be used in the future for the development of therapies,” says co-senior author Nicoletta Galeotti, PhD, associate professor of preclinical pharmacology at the University of Florence.

Source: Scripps Research Institute

Categories : Genetics Pain ManagementTags :

Whether Hypnosis for Pain is Effective Depends on a Patient’s Genetics

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Photo by Bruce Christianson on Unsplash

Studies have shown that hypnosis is an effective treatment for pain for many individuals – but it depends on the patient’s susceptibility to hypnosis. Testing for hypnotisability requires special training and in-person evaluation rarely available in the clinical setting. Now, investigators have developed a fast, point-of-care molecular diagnostic test that identifies a subset of individuals. Their study, published in The Journal of Molecular Diagnostics, also found that a subset of highly hypnotisable individuals may be more likely to experience high levels of postoperative pain.

“Since hypnotisability is a stable cognitive trait with a genetic basis, our goal was to create a molecular diagnostic tool for objectively identifying individuals who would benefit from hypnosis by determining ‘treatability’ at the point-of-care,” explained co-lead investigator Dana L. Cortade, a recently graduated PhD at Stanford University. “The advancement of nonpharmacological adjuvant treatments for pain is of the utmost importance in light of the opioid epidemic.”

Prior research established that the genetic basis for hypnotisability includes four specific single-nucleotide polymorphisms (SNPs), or genetic variations, found in the catechol-o-methyltransferase (COMT) gene for a brain enzyme responsible for dopamine metabolism in the prefrontal cortex. Although SNPs can contain valuable information on disease risk and treatment response, cost, complexity and time prevent widespread use.

The investigators developed a SNP genotyping assay on a giant magnetoresistive (GMR) biosensor array to detect the optimal combination of the COMT SNPs in patient DNA samples. GMR biosensor arrays are reliable, cheaper, sensitive, and can be easily deployed in point-of-care settings using saliva or blood samples.

The study investigated the association between COMT diplotypes and hypnotisability using a clinical hypnotisability scale called the Hypnotic Induction Profile (HIP) in individuals who had participated in one of the three previous clinical trials in which an HIP was administered. An additional exploratory study of the association between perioperative pain, COMT genotypes, and HIP scores was conducted with the patients in the third cohort, who had undergone total knee arthroplasty (TKA). DNA was extracted from blood samples previously collected in the first cohort, and saliva samples were collected by mail from participants in the other two trials. Participants were considered treatable by hypnosis if they had HIP scores of 3 or higher on a scale of zero to 10.

For participants identified with the optimal COMT diplotypes by the GMR biosensor array, 89.5% scored highly on the HIP, which identified 40.5% of the treatable population. The optimal COMT group mean HIP score was significantly higher than that in the suboptimal COMT group. Interestingly, further analysis revealed that the difference was observed only in women.

“Although we had expected some difference in effect between females and males, the association between hypnotisability and COMT genotypes was strongest in the females in the cohort,” said co-lead investigator Jessie Markovits, MD, Department of Internal Medicine, Stanford School of Medicine, Stanford, CA, USA. “The difference may be due to lower numbers of males in the cohort, or because COMT is known to have interactions with oestrogen and to differ in activity by sex. Additional gene targets including COMT, with stratification by sex, could be the focus of future study.”

In the exploratory analysis of the relationship between COMT genotypes and pain after TKA surgery, the same optimal COMT individuals had significantly higher postoperative pain scores than the suboptimal group, indicating a greater need for treatment. “This supports the body of evidence that COMT genotypes impact pain, and it is also known that COMT genotypes affect opioid use after surgery. Pain researchers can use this technology to correlate genetic predisposition to pain sensitivity and opioid use with response to an evidence-based, alternative remedy: hypnosis,” Dr Cortade said.

COMT SNPs alone are not a complete biomarker for identifying all individuals who will score highly on a hypnotisability scale and experience high pain sensitivity. The GMR sensor nanoarray can accommodate up to 80 SNPs, and it is possible that other SNPs, such as those for dopamine receptors, are needed to further stratify individuals.

The investigators observe that this study highlights the utility and potential of the evolving applications of precision medicine. “It is a step towards enabling researchers and healthcare professionals to identify a subset of patients who are most likely to benefit from hypnotic analgesia,” Dr Markovits said. “Precision medicine has made great strides in identifying differences in drug metabolism that can impact medication decisions for perioperative pain. We hope to provide similar precision in offering hypnosis as an effective, non-pharmacological treatment that can improve patient comfort while reducing opioid use.”

Source: Elsevier

Categories : Pain ManagementTags :

Spinal Degeneration Pain may Result from Damaged, Stiffened Ligaments

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Photo by Sasun Bughdaryan on Unsplash

From back pain to achy joints, musculoskeletal pain, while common, can be life-changing and debilitating. A recent study published by the Journal of Biomechanical Engineering reveals that, in spinal degeneration, stiffening ligaments can alter mechanical loading on joints resulting in facet joint pain. This research may help to develop new treatments for musculoskeletal pain.

“Our goal is to understand the degeneration process of musculoskeletal tissues, including cartilage, ligaments, and intervertebral discs, using advanced mechanics techniques,” says Jill Middendorf, an assistant professor of mechanical engineering at Johns Hopkins University. “If we understand why this process is happening, we hope to translate our findings into new methods to repair damaged tissues and prevent more pain,”

Middendorf and collaborators sought to understand how the soft tissues of the spine change as spinal discs break down, or degenerate, over time.

Specifically, they looked at the facet capsular ligament, a soft tissue that holds the two sides of the facet joint together and is thought to be a common cause of lower back pain. Previous studies suggest this could be related to mechanical changes that occur in this ligament during spinal degeneration, though it’s not clear exactly why, Middendorf says.

To find out, the team extracted facet capsular ligaments from cadaver spines and ran experiments to measure the ligament’s mechanical properties, like stress and strain, under different loading conditions. By comparing MRI images of the spine and their experimental results, the team discovered that the tissues in the ligament became stiffer as the spine degenerated.

The researchers think this increased stiffness causes altered loading in surrounding tissues, and may explain why some people experience facet joint pain.

“Here we show that there is a correlation between the mechanics of the ligament and spine degeneration, which brings us even closer to being able determine if this ligament is causing pain or if it’s some other part of the spine,” Middendorf says.

With insights gathered from their tissue experiments, researchers in Middendorf’s lab plan to work next on furthering our understanding of spinal degeneration and creating engineered musculoskeletal tissue that can be implanted to replace damaged or diseased tissue.

However, when it comes to pain, answers aren’t always easy to find.

“‘One of the challenges associated with diagnosing and treating spine pain is determining the source of the pain,” Middendorf says. “But we can understand more about the causes and mechanisms of tissue damage, and that means we will someday be able to reverse engineer a solution.”

Source: Johns Hopkins

Categories : Ageing Pain ManagementTags :

The Impacts of Persistent Pain in Older Adults

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Woman holding an old man's hand
Photo by Matthias Zomer on Pexels

In a study of 5589 US adults aged 65 years and older, persistent pain was common and was linked to meaningful declines in physical function and well-being over 7 years. Reporting in the Journal of the American Geriatrics Society, investigators found that 38.7% of participants reported persistent pain, and 27.8% reported intermittent pain. (“Persistent pain” was defined as being bothered by pain in the last month in two consecutive annual interviews and “intermittent” pain was defined as bothersome pain in one interview only.)  

More than one-third of participants described pain in five or more sites. Over the subsequent 7 years, participants with persistent pain were more likely to experience declines in physical function (64% persistent pain, 59% intermittent pain, 57% no bothersome pain) and well-being (48% persistent pain, 45% intermittent pain, 44% no bothersome pain), but were not more likely to experience cognitive decline (25% persistent pain, 24% intermittent pain, 23% no bothersome pain).

“The findings from this study point to the importance of access to effective treatment for persistent pain in older adults and the need for additional research in chronic pain to optimise quality of life,” said lead author Christine Ritchie, MD, MSPH, of Massachusetts General Hospital.

Source: Wiley

Categories : Pain ManagementTags :

Paracetamol and NSAIDs Best Non-opioid Drugs for Low Back Pain

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Acute low back pain is a common cause of disability, and while opioid drugs are effective at controlling pain, excessive use creates a great potential for substance abuse. An analysis in the Journal of Orthopaedic Research examined which non-opioid drugs are best for relieving this pain.

The analysis, which included all randomised controlled trials published to date (18 studies with 3478 patients), showed that muscle relaxants and non-steroidal anti-inflammatory drugs (NSAIDs) could effectively and rapidly reduce symptoms.

The combination of NSAIDs and paracetamol was associated with a greater improvement than NSAIDs alone.

“This is a first step towards the optimisation of the management of acute low back pain. However, specific patient characteristics such as having allergies and comorbidities must always be taken into consideration,” said lead author Alice Baroncini, MD, PhD, of RWTH University Hospital in Germany. “Further research will need to focus on the identification of the type of drugs that not only offer the best and quickest pain relief, but also show the lowest rate of symptom recurrence.”

Source: Wiley

Categories : Pain ManagementTags :

Brain Structures Predict Risk of Awareness under Anaesthesia

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Awareness during anaesthesia is an extremely rare but horrific risk for patients. Now, for the first time, neuroscientists have identified brain structures which could predict an individual’s predisposition this phenomenon. The findings, just published in the journal Human Brain Mapping, could help identify patients who need larger anaesthetic doses.

Although anaesthesia has been used in clinical medicine for over 150 years, scientists do not fully understand why its effect on people is so varied. One in four patients presumed to be unconscious during general anaesthesia may in fact have subjective experiences, such as dreaming. Estimated to occur in 1:1000 to 1:20 000 cases, some patients may have awareness under general anaesthetic. These experiences may range from hearing sounds to the pain of surgery combined with the sensation of suffocation and paralysis in the setting of neuromuscular blockade.

The researchers from Trinity College Dublin found that one in three participants were unaffected by moderate propofol sedation in their response times, thus thwarting a key aim of anaesthesia – the suppression of behavioural responsiveness.

The research also showed, for the first time, that the participants who were resistant to anaesthesia had fundamental differences in the function and structures of the fronto-parietal regions of the brain to those who remained fully unconscious. Crucially, these brain differences could be predicted prior to sedation.

Lorina Naci, Associate Professor of Psychology, Trinity who lead the research said:

“The detection of a person’s responsiveness to anaesthesia prior to sedation has important implications for patient safety and wellbeing. Our results highlight new markers for improving the monitoring of awareness during clinical anaesthesia. Although rare, accidental awareness during an operation can be very traumatic and lead to negative long-term health outcomes, such as post-traumatic stress disorder, as well as clinical depression or phobias.”

“Our results suggest that individuals with larger grey matter volume in the frontal regions and stronger functional connectivity within fronto-parietal brain networks, may require higher doses of propofol to become nonresponsive compared to individuals with weaker connectivity and smaller grey matter volume in these regions.”

The research, conducted in Ireland and Canada, investigated 17 healthy individuals who were sedated with propofol, the most common clinical anaesthetic agent. The participants’ response time to detect a simple sound was measured when they were awake and as they became sedated. Brain activity of 25 participants as they listened to a simple story in both states was also measured.

Source: Trinity College Dublin