Tag: chronic pain

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

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

Photo by Towfiqu Barbhuiya on Unsplash

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

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

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

Continuation of Opioids for Chronic Pain: Experts Divided

Photo by Usman Yousaf on Unsplash

Chronic pain is complex and difficult to treat. Prescribing opioid pain medications has become controversial but may help some patients.

With the goal of informing clinician practice, a new study explores the harms and benefits of continuing and of discontinuing the long-term prescription of opioid medicines to adults with chronic pain. The authors analysed the opinions of 28 experts on the harms versus benefits of maintaining, tapering or terminating opioid pain medication prescriptions for chronic pain, a common condition worldwide that is typically quite difficult to treat.

The study authors found a lack of consensus among the experts on how to treat chronic (lasting three or more months) non-cancer pain. Slightly more than a third of the experts (36%) believed that long-term opioid therapy is beneficial, while an equal percentage indicated that it should be discontinued.

More than half of the experts believed that patients can experience harm from overly rapid tapering and discontinuation, while some recommended attempting a slow taper (even with a prior unsuccessful taper), possibly with addition of medications to manage withdrawal) in order not to maintain opioid therapy.

Some of the experts advocated for switching patients to buprenorphine, which diminishes the effects of physical dependency to opioids, such as withdrawal symptoms and cravings, and is used to treat pain. Some considered adding non-opioid pain therapies (including re-trying these therapies even if they were unhelpful in the past) as well as engaging in shared decision-making with the patient, although there was little consensus on how to accomplish these options.

Some, but not all of the experts, noted the benefit of addressing co-occurring conditions related to patient safety, such as alcohol use, mental health symptoms and opioid side effects.

Few of the experts brought up assessing or addressing opioid use disorder or overdose risk.

“The potential harms of opioid pain medication are well known, nevertheless patients can become habituated to them and want their physicians to continue prescribing them. Taking patients off opiates may result in return or worsening of chronic pain, mental health issues, drug seeking and potentially overdose and death. Additionally, these drugs could be used by someone else, possibly winding up on the street,” said study co-author Kurt Kroenke, MD of the Regenstrief Institute and the Indiana University School of Medicine. “On the benefit side, these drugs may be helping relieve the patient’s often debilitating pain which can impact the ability to interact with family, to hold a job, participate in social activities and many other aspects of life.”

A substantial number of people who are prescribed opioid pain medications continue to experience chronic pain. Dr Kroenke notes that these individuals may be good candidates for tapering to a lower dose, prescription discontinuation and moving on to effective, safer treatments for pain.

The authors conclude their analysis of the experts’ opinions, “Guidelines on whether to continue or taper opioids prescribed long- term may be difficult to utilize given professional liability concerns, changing regulations and health system initiatives, differing provider-patient perspectives on long-term opioid benefits and harms, and some providers’ beliefs that opioid dependence interferes with patients’ objectivity. In the meantime, individual care decisions that involve weighing relative harms should draw on longstanding norms of ethical medical care that call for informed consent and patient-provider conversations grounded in mutual respect.”

The study is published in the peer-reviewed journal Pain Practice.

Source: EurekAlert

A Groundbreaking New Approach to Treating Chronic Abdominal Pain

Researchers at the University of Vienna develop gut-stable oxytocin analogues for targeted pain treatment of chronic abdominal pain

Photo by Andrea Piacquadio on Pexels

A research team at the University of Vienna, led by medicinal chemist Markus Muttenthaler, has developed a new class of oral peptide therapeutic leads for treating chronic abdominal pain. This groundbreaking innovation offers a safe, non-opioid-based solution for conditions such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD), which affect millions of people worldwide. The research results were published in Angewandte Chemie.

An innovative approach to pain management

Current medications used to treat chronic abdominal pain often rely on opioids. However, opioids can cause severe side effects such as addiction, nausea, and constipation. Additionally, they affect the central nervous system, often leading to fatigue and drowsiness, which impairs the quality of life of those affected. The addiction risk is particularly problematic and has contributed to the ongoing global opioid crisis. Therefore, there is an urgent need for alternatives that minimise these risks.

This new therapeutic approach targets oxytocin receptors in the gut, which, in addition to its role in social bonding, also affects pain perception. When the peptide hormone oxytocin binds to these receptors, it triggers a signal that reduces pain signals in the gut. The advantage of this approach is that the effect is gut-specific, thus having a lower risk of side effects due to its non-systemic, gut-restricted action.

Oxytocin itself cannot be taken orally because it is rapidly broken down in the gastrointestinal tract. However, Prof Muttenthaler’s team has successfully created oxytocin compounds that are fully gut-stable yet can still potently and selectively activate the oxytocin receptor. This means these newly developed oxytocin-like peptides can be taken orally, allowing for convenient treatment for patients. This approach is especially innovative since most peptide drugs (such as insulin, GLP1 analogues) need to be injected as they are also quickly degraded in the gut.

“Our research highlights the therapeutic potential of gut-specific peptides and offers a new, safe alternative to existing pain medications, particularly for those suffering from chronic gut disorders and abdominal pain,” explains Muttenthaler.

Next steps and future outlook

With support from the European Research Council, the scientists are now working to translate their research findings into practice. The goal is to bring these new peptides to market as an effective and safe treatment for chronic abdominal pain. Moreover, the general approach of oral, stable, and gut-specific peptide therapeutics could revolutionise the treatment of gastrointestinal diseases, as the therapeutic potential of peptides in this area has not yet been fully explored.

The team has already secured a patent for the developed drug leads and is now actively seeking investors and industrial partners to advance the drug leads towards the clinic.

Source: University of Vienna

First-visit Communication with Doctor Affects Outcomes of Pain Patients

Photo by Alex Green on Pexels

Chronic pain, defined as daily or significant pain that lasts more than three month, can be complicated to diagnose and treat. Studies have shown that, since chronic pain conditions are clouded with uncertainties, patients often struggle with anxiety and depression – something challenging to for they and their doctors to discuss and manage.

A recent study of 200 chronic neck or back pain sufferers found that effective physician-patient communication during the initial consultation helps patients manage their uncertainties, including their fears, anxieties and confidence in their ability to cope with their condition.

Study leader Charee Thompson, communication professor at University of Illinois Urbana-Champaign, said: “We found that providers and patients who perceive themselves and each other as competent medical communicators during consultations can alleviate patients’ negative feelings of uncertainty such as distress and increase their positive feelings about uncertainties such as their sense of hope and beliefs in their pain-management self-efficacy. Providers and patients successfully manage patients’ uncertainty through two fundamental medical communication processes – informational and socioemotional, each of which can have important clinical implications.”

According to the study, informational competence reflects patients’ abilities to accurately describe their symptoms and verify their understanding of doctors’ explanations and instructions, as well as clinicians asking appropriate questions, providing clear explanations and confirming patients’ understanding. The extent to which doctors and patients establish a trusting relationship through open, honest communication and patients’ feelings of being emotionally supported by the physician reflects socioemotional communication competence.

Thompson and her co-authors — Manuel D. Pulido, a communication professor at California State University, Long Beach; and neurosurgery chair Dr. Paul M. Arnold and medical student Suma Ganjidi, both of the Carle Illinois College of Medicine — published their findings in the Journal of Health Communication.

The current study was based on uncertainty management theory, the hypothesis that people faced with uncertainty about a health condition appraise it and decide whether obtaining information is a benefit or a threat. For example, patients may seek information about the origins of a new symptom to mitigate their anxiety-related uncertainty — or, conversely, they might avoid information-seeking so they can maintain hopeful uncertainty about their prognosis, the team wrote.

The study was conducted at an institute in the Midwest composed of several clinics and programs that treat diseases and injuries of the brain, spinal cord and nervous system. Ranging in age from 18–75, those in the study sample had pain that included but was not limited to their neck, back, buttocks and lower extremities. About 59% of the patients were female. 

Before the consultation, the patients completed surveys rating how they experienced and managed their pain and their certainty or uncertainty about it. They and the providers also completed post-consultation surveys rating themselves and each other on their communication skills. 

The patients rated how well the provider ensured that they understood their explanations and asked questions related to their medical problem. 

To determine if patients’ levels of uncertainty changed, on the pre- and post-consultation surveys the patients ranked how certain or uncertain they felt about six aspects of their pain – including its cause, diagnosis, prognosis, the available treatment options and the risks and benefits of those. The patients also rated themselves on catastrophising – their tendency to worry that they would always be in pain and never find relief.

Patients’ feelings of distress were reduced when they and their physician mutually agreed that the other person was effective at seeking and providing medical information, and when the patients felt emotionally supported by their doctors, the team found.

“Patients’ ratings of their providers’ communication competency significantly predicted reductions in their pain-related uncertainty and in their appraisals of fear and anxiety, as well as increases in their positive uncertainty and pain self-efficacy,” Thompson said. “Providers’ reports of patients’ communication competency were likewise associated with decreases in patients’ pain-related uncertainty and marginally significant improvements in their positive appraisals of uncertainty.”

In a related study, the U. of I.-led team found that, for a subset of spinal pain patients, satisfaction, trust in and agreement with their doctor were strongly associated with the doctors exceeding patients’ expectations for shared decision-making and the quality of the provider’s history-taking and people skills. U. of I. graduate student Junhyung Han was a co-author of that paper, which was published in the journal Patient Education and Counseling

The team wrote that providers and patients need to discuss their mutual expectations for testing, medication and treatment, such as which options are worth pursuing and their potential to meet patients’ expectations for pain relief. 

Thompson said that while these studies’ findings highlight the effects that providers’ overall communication skills have on chronic pain patients’ emotions, expectations and attitudes about their condition, the patients’ communication skills matter, too. 

“I wanted to challenge the notion that pain patients are frustrated or ‘difficult’ because they have unrealistic standards,” Thompson said. “No matter how high their expectations are, what seems to matter most to conversation outcomes is the extent to which patients’ expectations are met or exceeded.

“Consultations mark what may be a long, challenging diagnostic and treatment journey for these patients, and they could benefit from learning about therapies and strategies to help them manage their pain and uncertainties,” Thompson said. “Giving them the tools and language to communicate their symptoms and concerns to providers could make their interactions more productive. Learning about the uncertain nature of pain may validate their fears and anxieties, while awareness and education about the various treatment options and therapies such as cognitive behavioural therapy could enhance their coping and dispel feelings of helplessness and fear.”

Source: University of Illinois at Urbana-Champaign

Radiology Helps Treat Chronic Pain

Dr Winter performing a CT-guided interventional procedure. Photo: Supploed

Radiology encompasses more than just imaging. It is a medical field that uses various imaging techniques to diagnose conditions, guide minimally invasive procedures and, much to the relief of agonised patients, treat chronic pain.

‘Traditionally, radiology is known as a modality where causes of pain are only diagnosed’, says Dr Arthur Winter, a radiologist at SCP Radiology. ‘Interventional radiology has changed this. It is a rapidly developing branch of radiology involving minimally invasive procedures.  Pain management procedures are becoming a daily part of busy radiology departments.’

Simply put, interventional radiologists can use precisely targeted injections to intervene in the body’s perception of pain.

Understanding pain

Pain is a signal from the nervous system to let you know that something is wrong in your body. It is transmitted in a complex interaction between specialised nerves, the spinal cord and the brain. It can take many forms, be localised to one part of the body or appear to come from all over.

Pain can be acute or chronic

Harvard Medical School gives an overview of the difference between the two. ‘Most acute pain comes from damage to body tissues. It results from physical trauma such as a sports or exercise injury, a broken bone, a medical procedure or an accident like stubbing your toe, cutting a finger or bumping into something. The pain can feel sharp, aching or throbbing and often heals within a few days to a few weeks.’

In comparison, chronic pain lasts at least two to three months, often long after you have recovered from the injury or illness and may even become permanent. It could also be a result of lifestyle diseases. Symptoms and severity vary and may include a dull ache, shooting, burning, stabbing or electric shock-like pain and sensations like tingling and numbness. Chronic pain can be debilitating and affect your ability to perform activities of daily living.

Interventional pain management

Although some acute pain can be managed with interventions, it is patients with chronic pain that truly benefit. ‘These patients often use high doses of opioid painkillers that may cause nausea, constipation, anorexia and addiction. Other painkillers may also irritate the stomach lining and cause kidney problems,’ says Dr Winter.

An alternative that interventional pain management offers, involves injections called nerve blocks that target very specific nerves.

‘Most of these interventions prevent nerve impulses or pain signals from being transmitted, using long-acting local anaesthetics. The effect is usually temporary but the addition of cortisone – or steroids – often brings longer-lasting relief. In some cases, it could be appropriate to follow the temporary block with neurolysis, which is a permanent disruption or destruction of the target nerves.’

Although nerve blocks and other long-acting pain injections have been done for years, the scope of procedures is evolving fast. The involvement of radiologists has also grown.

Dr Winter explains. ‘Pain management has traditionally been the responsibility of clinicians and anaesthetists. During nerve block procedures, they were typically guided by their knowledge of anatomy or a continuous X-ray technique called fluoroscopy. As ultrasound became more widely available, many anaesthetists learned to do these procedures under ultrasound guidance.

‘These specialists still provide these treatments but, thanks to the availability of specialised imaging equipment, radiologists now have the tools and skill to do procedures under sophisticated image guidance. With CT guidance, some procedures can be performed with great accuracy while avoiding blood vessels and non-target organs,’ says Dr Winter.

‘A lower dose of medication is also needed if the needle is placed accurately next to the target nerves. It is therefore not surprising that this is increasingly becoming a responsibility of interventional radiologists.’

Other procedures where radiologists are involved include targeted Botox injections to treat the symptoms of Piriformis syndrome, epidural cortisone injections for inflammation in the spine and a procedure called epidural blood patch. This is to seal spinal fluid leaks that cause low-pressure headaches.

In conclusion, Dr Winter says chronic pain may cause poor quality of life and depression, often seen in patients with underlying cancer. ‘It is especially these patients who should be considered for interventions. There are, for example, very effective procedures to manage pain caused by pancreatic and pelvic cancers.

‘Specialists like oncologists and neurologists recognise the value of interventional radiology in pain management and work closely with us to support their patients. It is a growing branch of radiology that offers a minimally invasive solution and it’s quite rewarding to see patients regain some quality of life.’

Researchers Delve into the Roots of Chronic Pain

Source: Pixabay CC0

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

Dependence on Pain Medication is on the Rise

Photo by Towfiqu Barbhuiya on Unsplash

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

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

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

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

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

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

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

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

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

Source: University of Surrey

Chronic Back Pain may be Easier to Treat if it’s ‘in the Brain’

Photo by Sasun Bughdaryan on Unsplash

One therapy for chronic back pain is to teach patients how to ‘reprocess’ it in the brain. Now, this therapy may become even more effective thanks a study published in JAMA Network Open. The study examined the critical connection between the brain and pain for treating chronic pain. Specifically, they looked at the importance of pain attributions, which are people’s beliefs about the underlying causes of their pain, to reduce chronic back pain severity. Understanding the source of the pain may help some to avoid surgery which may be ineffective or even worsen the pain.

“Millions of people are experiencing chronic pain and many haven’t found ways to help with the pain, making it clear that something is missing in the way we’re diagnosing and treating people,” said the study’s first author Yoni Ashar, PhD, assistant professor of internal medicine at the University of Colorado Anschutz Medical Campus.

Pain is often in the brain

Ashar and his team tested whether the reattribution of pain to mind or brain processes was associated with pain relief in pain reprocessing therapy (PRT), which teaches people to perceive pain signals sent to the brain as less threatening. Their goal was to better understand how people recovered from chronic back pain. The study revealed after PRT, patients reported reduced back pain intensity.

“Our study shows that discussing pain attributions with patients and helping them understand that pain is often ‘in the brain’ can help reduce it,” Ashar said.

To study the effects of pain attributions, they enrolled over 150 adults experiencing moderately severe chronic back pain in a randomised trial to receive PRT. They found that two-thirds of people treated with PRT reported being pain-free or nearly so after treatment, compared to only 20% of placebo controls.

“This study is critically important because patients’ pain attributions are often inaccurate. We found that very few people believed their brains had anything to do with their pain. This can be unhelpful and hurtful when it comes to planning for recovery since pain attributions guide major treatment decisions, such as whether to get surgery or psychological treatment,” said Ashar.

Before PRT treatment, only 10% of participants’ attributions of PRT treatment were mind- or brain-related. However, after PRT, this increased to 51%. The study revealed that the more participants shifted to viewing their pain as due to mind or brain processes, the greater the reduction in chronic back pain intensity they reported.

The role of discussing brain drivers of chronic pain 

“These results show that shifting perspectives about the brain’s role in chronic pain can allow patients to experience better results and outcomes,” Ashar adds.

Ashar says that one reason for this may be that when patients understand their pain as due to brain processes, they learn that there is nothing wrong with their body and that the pain is a ‘false alarm’ being generated by the brain that they don’t need to be afraid of.

The researchers hope this study will encourage providers to talk to their patients about the reasons behind their pain and discuss causes outside of biomedical ones.

“Often, discussions with patients focus on biomedical causes of pain. The role of the brain is rarely discussed,” said Ashar. “With this research, we want to provide patients as much relief as possible by exploring different treatments, including ones that address the brain drivers of chronic pain.”

Source: University of Colorado Anschutz Medical Campus

The Impacts of Persistent Pain in Older Adults

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