Pain Management

Posted on Pain Management

Brain scans shoe that mindfulness for pain is not a placebo

brian scan

Credit UC San Diego Health Sciences

Pain is a complex and multi-dimensional experience influenced by factors beyond just physical sensation, including a person’s mindset and their expectations of pain. The placebo effect, where symptoms improve in response to inactive treatment, demonstrates how expectations can significantly impact a person’s experience. Mindfulness meditation, which has been used for pain management in various cultures for centuries, was previously believed to work by triggering the placebo response. However, recent scientific findings have disproven this belief.

A recent study published in Biological Psychiatry discovered that mindfulness meditation activates specific brain mechanisms that differ from those involved in the placebo response, leading to a reduction in pain. Researchers at the University of California San Diego School of Medicine utilized advanced brain imaging methods to compare the pain-relieving effects of mindfulness meditation, a placebo cream, and a “sham” mindfulness meditation among healthy participants.

The research discovered that mindfulness meditation led to notable decreases in both the intensity and unpleasantness of pain, as well as a reduction in brain activity linked to pain and negative emotions. On the other hand, the placebo cream only affected brain activity related to the placebo effect without changing the person’s actual experience of pain.

“The mind is incredibly powerful, and we are still trying to understand how it can be used for managing pain,” said Fadel Zeidan, PhD, a professor of anesthesiology and Endowed Professor in Empathy and Compassion Research at UC San Diego Sanford Institute for Empathy and Compassion. “By separating pain from the self and letting go of judgment, mindfulness meditation can directly change how we experience pain. It does not involve any drugs, costs nothing, and can be practiced anywhere.”

The study involved 115 participants who took part in two separate clinical trials. The participants were randomly assigned to different groups to receive one of four interventions: guided mindfulness meditation, a sham mindfulness meditation involving only deep breathing, a placebo cream (petroleum jelly) that participants were told reduces pain, and, as a control, listening to an audiobook. The researchers applied a mildly painful but harmless heat stimulus to the back of the leg and scanned the participants’ brains before and after the interventions.

The researchers utilized a new method known as multivariate pattern analysis (MVPA) to examine the brain activity patterns of the participants. This method uses machine learning to understand the complex neural mechanisms linked to the sensation of pain. These mechanisms involve specific responses to heat stimuli, negative emotions, and pain reactions induced by the placebo effect. Using this approach, the researchers could ascertain whether mindfulness meditation and the placebo effect trigger similar or different brain processes.

Although both the placebo cream and sham mindfulness meditation reduced pain, the study revealed that mindfulness meditation was significantly more effective in pain reduction compared to the placebo cream, sham mindfulness meditation, and the controls.

They found that mindfulness-based pain relief reduced synchronization between brain areas involved in introspection, self-awareness, and emotional regulation. These areas of the brain make up the neural pain signal (NPS), a recognized pattern of brain activity associated with pain across different individuals and types of pain. On the other hand, the placebo cream and sham mindfulness meditation did not show a significant change in the NPS compared to the controls. Instead, these interventions engaged entirely separate brain mechanisms with little overlap.

“It has been widely believed that the placebo effect and the brain mechanisms activated by actual treatments are closely linked. However, these findings indicate that this may not be the case when it comes to pain,” explained Zeidan. “Instead, these two brain responses are entirely separate. This supports the idea of using mindfulness meditation as a direct treatment for chronic pain, rather than as a means of triggering the placebo effect.”

In modern medicine, new therapies are considered effective and reliable if they perform better than a placebo. A recent study discovered that mindfulness meditation is more effective than a placebo and does not activate the same neurobiological processes. These findings are significant for developing new treatments for chronic pain. However, further research is needed to confirm these effects in individuals with chronic pain as opposed to healthy participants.

The researchers aim to use their understanding of the specific brain mechanisms involved in mindfulness meditation to create better interventions. These interventions could be more effective and accessible and could help reduce pain in people with different health conditions.

“Millions of people live with chronic pain every day, and there may be more that these individuals can do to reduce their pain and enhance their quality of life than we previously understood,” said Zeidan. “We are excited to continue exploring the neurobiology of mindfulness and how we can utilize this ancient practice in the clinic.”

Posted on Pain Management

“Ultrasound device shows promise for treating chronic pain.”

Diadem

University of Utah engineers developed Diadem, a noninvasive device that stimulates deep brain regions to potentially disrupt faulty signals causing chronic pain. (Credit: University of Utah)

Pain is a necessary biological signal, but a variety of conditions can cause those signals to go awry. For people with chronic engineers at the University of Utah have developed Diadem, a noninvasive device that can stimulate deep brain regions to potentially disrupt faulty signals causing chronic pain. Chronic pain often arises from faulty signals deep within the brain, which can persist even after the original injury has healed or a limb has been amputated. The University of Utah’s new device, Diadem, has shown promising results in providing relief to participants after just one treatment session. The device uses ultrasound to noninvasively stimulate deep brain regions, potentially disrupting the faulty signals that lead to chronic pain

.A recent clinical trial published in the journal Pain showed that 60% of the participants who received real treatment reported a significant reduction in symptoms one day and one week after the treatment. This unexpected rapid onset of pain symptom improvements and their sustained nature open doors for applying these noninvasive treatments to many patients who are resistant to current treatments.

Diadem’s approach is based on neuromodulation, a therapeutic technique that directly regulates the activity of certain brain circuits. Unlike other neuromodulation approaches, Diadem’s ultrasound stimulation can selectively reach the specific brain structure known as the anterior cingulate cortex, which was the focus of the researchers’ recent trial. The team is now preparing for a Phase 3 clinical trial, the final step before seeking approval from the Food and Drug Administration to use Diadem as a treatment for the general public. They are actively looking to recruit participants for the upcoming trial, and they believe that with more help, chronic pain can be effectively silenced, potentially offering new treatment options to tackle the opioid crisis as well. If you or your relatives suffer from chronic pain that does not respond to current treatments, the research team encourages reaching out to them for potential participation in the trials.

Patients suffering from life-altering pain are constantly seeking new treatment options. A new device developed by the University of Utah may finally provide a practical, long-awaited solution.

At the core of this research is Diadem, a new biomedical device that uses ultrasound to noninvasively stimulate deep brain regions, potentially disrupting the faulty signals that lead to chronic pain.

The study was conducted by Jan Kubanek, a professor in Price’s Department of Biomedical Engineering, and Thomas Riis, a postdoctoral researcher in his lab. They collaborated with Akiko Okifuji, professor of Anesthesiology in the School of Medicine, as well as Daniel Feldman, a graduate student in the departments of Biomedical Engineering and Psychiatry, and Adam Losser, a laboratory technician.

“We did not anticipate such potent and immediate effects from just one treatment,” stated Riis.

“The rapid onset of the pain symptom improvements as well as their sustained nature is interesting, and opens doors for applying these non-invasive treatments to the many patients who are resistant to current treatments,” Kubanek added.

Please take note of the following text: Diadem’s approach is founded on neuromodulation, which is a therapeutic technique aiming to directly regulate the activity of specific brain circuits. While other neuromodulation methods rely on electric currents and magnetic fields, they are unable to selectively target the brain structure examined in the researchers’ recent trial: the anterior cingulate cortex.

Following an initial functional MRI scan to map the target region, the researchers adjusted Diadem’s ultrasound emitters to account for the way the waves deflect off the skull and other brain structures. This procedure was published in Nature Communications Engineering.

“If you or your relatives suffer from chronic pain that does not respond to treatments, please reach out to us. We need to recruit many participants so that these treatments can be approved for the general public,” Kubanek said. “With your help, we believe chronic pain can be effectively managed. Additionally, with new pain treatment options, we can help address the opioid crisis as well.”

Posted on Pain Management

Making pain treatment more individual

Ways to manage chronic pain

Severe pain is often attributed to physical causes. However, emotional, psychological, and social factors can also impact how we experience and respond to pain. Noemi Gozzi, a doctoral student at ETH Zurich, explains that pain typically consists of both a physical and a psychosocial component.

Physicians strive to consider this when making treatment recommendations. However, distinguishing one component from the other has been challenging. Physicians often use straightforward methods to assess pain and its severity, relying on the patient’s subjective descriptions. This can result in nonspecific treatments. Despite their drawbacks such as adverse effects, reduced effectiveness over time, and the potential for addiction or overdose, opioid painkillers continue to be widely used.

Making treatment more individual

In recent years, Stanisa Raspopovic’s group at ETH Zurich, which includes Gozzi, has collaborated with researchers at Balgrist University Hospital in Zurich to create a new approach to effectively differentiate and measure the physical and psychosocial aspects of pain. They have published their new method in the current issue of the journal Med. Raspopovic was formerly a professor of Neuroengineering at ETH Zurich.

“Our new approach should help physicians assess patients’ pain more individually, allowing for more personalized treatment in the future,” Raspopovic states. If the pain is mainly physical, doctors are likely to focus treatment on the physical aspect, including the use of medications or physiotherapy. Alternatively, if psychosocial factors significantly contribute to the patient’s pain experience, it may be beneficial to address the perception of pain through psychological or psychotherapeutic support.

Large dataset

To develop the new method, the researchers analyzed data from 118 volunteers, including people with chronic pain as well as healthy controls. The researchers asked the study participants in detail about their perception of pain and any psychosocial characteristics such as depression, anxiety, and fatigue. They also inquired about the frequency with which the participants experienced pain that prevented them from going to work. Additionally, the researchers assessed the participant’s ability to distract themselves from pain and examined the extent to which pain led them to ruminate or feel helpless, causing them to overestimate the intensity of the pain.

The researchers used standardized measurements to compare the subjects’ perceptions of pain. Participants received small, non-dangerous but painful pulses of heat on their skin. To record the physical reaction to the pain, the researchers measured the study participants’ brain activity using an electroencephalogram (EEG) and the skin’s electrical conductivity, which changes depending on how much someone is sweating and is used to measure stress, pain, and emotional arousal. The extensive dataset also included the diagnoses of the study participants, which the researchers at Balgrist University Hospital made.

Machine learning delivers precision medicine.

Machine learning has assisted researchers in analyzing a large amount of data, enabling them to clearly distinguish between the two components of pain and develop a new index for each. The index for the physical component of pain indicates the extent to which physical processes cause the pain, while the index for the psychosocial component indicates how strongly emotional and psychological factors intensify the pain. Finally, the scientists validated these two factors using comprehensive measurement data from the participants.

The new method combines measuring body signals, self-disclosure, computerized evaluation, and the resulting two indices. It is intended to help physicians treat pain. “Our method enables physicians to precisely characterize the pain a particular person is suffering, so they can better decide what kind of targeted treatment is needed,” says Gozzi.

Posted on Fibromyalgia, Pain Management

CBT eases how fibromyalgia pain is experienced by the brain

A randomized, controlled trial led by Mass General Brigham researchers demonstrates that cognitive behavioral therapy can significantly reduce the impact of fibromyalgia pain
A randomized, controlled trial led by Mass General Brigham researchers demonstrates that cognitive behavioral therapy can significantly reduce the impact of fibromyalgia pain

Individuals with fibromyalgia often face limited treatment options and struggle to find explanations for their symptoms. Researchers at Mass General Brigham have discovered that cognitive behavioural therapy (CBT) can significantly alleviate the burden of fibromyalgia by reducing pain-catastrophizing, a negative cognitive and emotional response that can intensify pain. Neuroimaging data showing decreased connectivity between brain regions associated with self-awareness, pain, and emotional processing support this finding.

“In this study, we examined how psychological processes and the brain’s connectivity patterns respond to pain,” stated co-senior author Robert Edwards, PhD, a clinical psychologist in the Department of Anesthesiology, Perioperative & Pain Medicine at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “We sought to investigate how cognitive behavioral therapy (CBT), a type of talk therapy aimed at addressing maladaptive thoughts, can improve daily functioning and change the brain’s processing of pain-related information.”

Edwards explains that cognitive behavioral therapy (CBT) can reduce negative cognitive and emotional responses to pain. He says that while these responses are normal, they can amplify the disabling effects of chronic pain and make conditions like fibromyalgia (FM) more burdensome.

The research team for the study included researchers from three members of Mass General Brigham: Spaulding Rehabilitation Hospital, Brigham and Women’s Hospital, and Massachusetts General Hospital. Mass General Brigham brings together 16 member institutions, including academic medical centres, top-tier speciality hospitals, community hospitals, and more. Research that involves multiple entities within Mass General Brigham provides unique insights and perspectives from different settings and areas of expertise, making it more impactful than individual research efforts.

:Researchers recruited 98 women, randomly assigning 64 to a treatment group receiving CBT and 34 to a control group that received education about FM and chronic pain but was not taught specific CBT techniques. All participants were between 18 and 75 years old and had a confirmed diagnosis of fibromyalgia for at least six months. To collect baseline data, all participants completed several validated pain and quality of life questionnaires.

During the study, each group took part in eight intervention sessions, which involved 60-75 minute visits with a licensed mental health provider. The participants were mainly evaluated based on their pain interference levels, which measures the extent to which their pain affected their daily activities, as well as their pain catastrophizing, pain severity, and the overall impact of fibromyalgia on their quality of life.

Results demonstrated that those who underwent CBT experienced significantly greater reductions in pain interference. CBT participants also exhibited significantly less pain catastrophizing and reported that their FM symptoms had significantly less impact on their daily lives.

The team saw evidence that after undergoing CBT, patients experienced changes in the activities of all three networks that suggested a diminished focus on pain.

“Before undergoing cognitive behavioral therapy (CBT), we observed strong connections in certain parts of the brain related to self-awareness and sensation, indicating that patients were highly attuned to the pain they were feeling and internalized these symptoms,” said co-first author Jeungchan Lee, PhD, an instructor in the Department of Physical Medicine and Rehabilitation at Spaulding Rehabilitation Hospital and the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital. “After CBT, these connections were significantly weaker, suggesting that patients were better able to separate themselves from their pain after therapy.”

This study was limited to women, partly because of its high prevalence, and partly to eliminate confounding gender differences in brain activity. In the future, the researchers hope to collect data from men and non-binary patients with FM. Additionally, CBT includes several therapeutic components, and these results cannot be generalized to assess the impact across all forms of CBT on reducing FM chronic pain.

Both Lee and Edwards agree that these findings ultimately suggest that complex chronic pain conditions like fibromyalgia should be addressed with a multitude of pharmacological and cognitive therapies.

“I hope that these findings motivate healthcare providers to consider CBT as an effective treatment option to reduce the impact of pain patients experience,” explained Edwards. “Chronic pain conditions like fibromyalgia involve long-standing patterns of changes in the central nervous system, and CBT is one among many treatment options, such as medication and physical therapy, that we know can be beneficial for those living with FM.”

Posted on Pain Management

“The body’s immune response may provide an alternative approach to treating neuropathic pain.”

NK cells and neuropathic pain

This diagram shows how NK cell function could, in theory, result in the resolution of neuropathic pain in the context of peripheral nerve injury by directed cytotoxicity against many pathological cellular targets. CREDIT Kim et al./Trends in Neurosciences

A team of scientists is exploring natural killer (NK) cells as an alternative treatment for neuropathic pain. In an Opinion piece published June 27th in the journal Trends in Neurosciences, the researchers gather existing evidence for the impact of NK cells in pain, pointing to their ability to prune the damaged nerve cells that may cause it. They urge the scientific community to explore biological mechanisms underlying NK cell activity to move towards a realistic, effective, safe pain therapy.

Neuropathic pain is a chronic condition experienced as a recurring shooting or stabbing sensation. It is caused by nerve damage, which may occur because of trauma, a disease such as diabetes, or after chemotherapy.

“The prevalence of neuropathic pain is unfortunately only likely to increase over time,” says co-author Alexander Davies, a neurophysiologist with the Neural Injury Group at Oxford University. “As we get better at treating diseases like cancer, we have survivors who may be left with pain from either the cancer treatment or the surgery that was used to remove it.”

While therapies such as opioids and antidepressants are currently used to address these pain symptoms, they do not treat the underlying cause of pain and have their own risks and side effects. The authors point out that 564,000 people overdosed on opioids in the United States between 1999 and 2020.

“The main approach is silencing the neurons,” Davies says. “While we certainly need anaesthetics to deal with pain in the short term, if we use them in the long term, we can become addicted to the sensation of removing pain, which is in itself pleasurable.”

Alongside T cells and B cells, NK cells are a type of white blood cell called lymphocytes. Their existing role in the body includes attacking tumors or viruses. NK cells increase activity during acute pain. However, they appear to decline in frequency or potency in people who experience chronic pain. Not having a fully functional NK cell population may therefore prevent people from resolving neuropathic pain in the long term.

“We first became interested in this idea when one of my colleagues found a T cell response after nerve injury, but I noticed that NK cells were also involved,” says senior author Seog Bae Oh, a neurobiologist at Seoul National University. “NK cells are typically explored in the context of cancer, but I thought it was worth looking at them in pain as well.”

NK cells may resolve pain because they are involved in the process by which neurons are pruned. Injury and disease can cause neurons to become incorrectly wired or to stop functioning as intended, resulting in pain symptoms. Introducing NK cells could help to remove these anomalies. Experiments in mice have shown that if a neuron is in distress, its axon, the segment responsible for transmitting messages, displays a molecule called the RAE1 stress ligand. This could alert the NK cells to their need for pruning. A similar ligand, belonging to what is known as the ULBP family, is also seen in sensory neurons in humans with pain.

Conversely, NK cells may have a negative effect in the central nervous system, such as the brain and spinal cord, where neurons cannot regenerate so easily if they are removed. Their impact here should be considered carefully in the design of any possible therapies.

The authors stress that our understanding of the processes by which NK cells support pain relief is still limited, and their potential viability as a future treatment depends on further research. Both Davies and Oh are continuing to explore their NK cells in pain. Oh and his colleagues are investigating the therapeutic potential of NK cells in a range of preclinical models as well as their activity in patients who experience pain, while Davies is working to identify the cellular targets of NK cells following nerve injury.

“We need to have a better mechanistic understanding of how NK cells work and what they can target before we can develop realistic therapies, and we need to minimize their side effects,” Davies says. “However, the more prongs we have to treat neuropathic pain, the more likely we are ultimately to be able to address it.”