In this video, I discuss the treatment of neuropathic pain in multiple sclerosis.
Pain Management
Abdominal fat linked to chronic pain, especially in women
Reducing excess fat deposits in the abdomen may help reduce chronic musculoskeletal pain, especially if it’s experienced at multiple body sites, suggest the researchers. Previously published research has shown that obesity is associated with musculoskeletal pain. Still, it’s not known if excess fat tissue is linked to chronic musculoskeletal pain at multiple body sites, say the researchers. To find out, they drew on data from 32,409 participants in the UK Biobank study who completed questionnaires and underwent health assessments. Around half (51%) were women, and their average age was 55.
They underwent MRI scans of their abdomen to measure the amount of fat around the abdominal organs (visceral adipose tissue or VAT) and the amount of fat just under the skin that can be pinched (subcutaneous adipose tissue or SAT). When attending for their scan, participants were asked if they had experienced any pain in their neck/shoulder, back, hip, knee or ’all over the body’ for more than 3 months. The MRI scan and pain assessments were repeated around 2 years later for 638 participants. Comprehensive analyses showed a dose-response association between the number of chronic pain sites and VAT, SAT, the ratio of the two, and weight (BMI). The association was stronger in women, among whom the odds ratio of a higher number of chronic pain sites was twice as high for VAT and 60% greater for both SAT and the VAT: SAT ratio. In men, these odds ratios were 34% 39%, and 13% higher, respectively.
Higher levels of fat tissue were also associated with greater odds of reporting chronic pain, and again the association was more pronounced in women. All these associations remained even after adjusting for age, height, ethnicity, household income, educational attainment, alcohol intake, smoking status, physical activity, coexisting conditions, sleep duration, psychological problems and length of follow-up.
This is an observational study, and as such, can’t establish cause and effect, and the authors also acknowledge various limitations. These include the relatively small size of the repeat imaging sample and the absence of an assessment of severity in the pain questionnaire. They add that more follow-up visits would also have allowed more information to be gathered on patterns and fluctuations in the number of chronic pain sites. However, they conclude: “Abdominal adipose tissue was associated with chronic musculoskeletal pain, suggesting that excessive and ectopic fat depositions may be involved in the pathogenesis of multisite and widespread chronic musculoskeletal pain. Therefore, reducing abdominal adiposity may be considered a target for chronic pain management, particularly in those with pain in multiple sites and widespread pain.” They suggest that the stronger associations seen in women may be a consequence of sex differences in fat distribution and hormones.
Brain scans shoe that mindfulness for pain is not a placebo
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.”
“Ultrasound device shows promise for treating chronic pain.”
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.”
Making pain treatment more individual
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.