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.”

Posted on Rheumatoid arthritis

“Having a high BMI increases the risk of developing several rheumatic diseases, but the risk is not the same for everyone.”

Tips for successful dieting
Tips for successful dieting

A recent study from Uppsala University indicates that having a higher body mass index (BMI) can raise the risk of developing five different rheumatic diseases: rheumatism, osteoarthritis, gout, psoriatic arthritis, and inflammatory spondylitis. The researchers also observed that BMI posed a more significant risk factor for women in terms of gout and psoriatic arthritis, compared to men. The study will be featured in the journal Arthritis & Rheumatology.

“Understanding the risks associated with rheumatic diseases can help show that maintaining a lower body weight may be an effective intervention to reduce the risk of developing these conditions,” explained Weronica Ek, a Docent and Researcher at the Department of Immunology, Genetics, and Pathology at Uppsala University, who led the study. “Most rheumatic diseases are driven by inf…”Most rheumatic diseases are driven by inflammation in the body and mainly affect joints, muscles and bones, but vital organs and vessels can also be affected. Symptoms of rheumatic disease can include fatigue, swelling and pain in the joints, stiffness and reduced movement function.

Previous studies have revealed a link between rheumatic diseases and a high BMI, which is a measure that adjusts body weight according to the individual’s height. However, it has not been thoroughly explored whether this connection is a result of high BMI causing rheumatic disease, or if patients with rheumatic disease simply tend to have a higher BMI due to other unidentified reasons. This issue is frequently encountered in epidemiological studies that rely on observational data.

“The researchers in a recent study attempted to address the issue by utilizing information found in human genes. They focused on specific genetic variants linked to a high BMI and found that individuals with a genetic predisposition to higher BMI are at a greater risk of developing rheumatic disease.”“Although we have seen this connection in the past, it is difficult to identify the causal relations between BMI and disease. But when we found that the genes linked to high BMI were also associated with a higher risk of these rheumatic diseases, we were able to conclude that BMI truly does have an impact on the risk of developing rheumatic disease,” notes Ek.

The researchers employed the genetic method called Mendelian randomization to investigate differences between men and women. They also explored potential variations in how BMI impacts the risk for women of childbearing age compared to those who have undergone menopause.

“For both gout and psoriatic arthritis, which are common diseases in patients with psoriasis, we found that a high BMI was a stronger risk factor for women than for men. We also observed that the impact of BMI on the risk of developing osteoarthritis was lower in post-menopausal women compared to women of childbearing age,” explained Fatemeh Hadizadeh, Postdoctoral Fellow at the Department of Immunology, Genetics and Pathology, Uppsala University, and one of the main authors of the study.

The researchers also found that a certain increase in BMI did not result in an equal increase in the risk of developing gout among individuals with low, normal and high BMI.

“We observed that an increase in BMI among individuals with a normal weight led to a significantly higher relative increase in the risk of developing gout compared to an increase in BMI among individuals who are already overweight or obese. This implies that the risk does not increase as much for those who are already overweight. However, it’s important to note that the basic risk of developing gout is always higher with a higher BMI. These non-linear effects are intriguing from a molecular biological perspective and can help us understand the underlying mechanisms behind the increased disease risk associated with higher body weight,” explains Torgny Karlsson, a Statistician at the Department of Immunology, Genetics, and Pathology at Uppsala University and one of the lead authors of the study.

Posted on Alzheimer's, Diabetes

“Possible explanation for a link between diabetes and Alzheimer’s”

Olov Rolandsson portrait

Professor Olov Rolandsson, Department of Public Health and Clinical Medicine, Umeå University Credit Mattias Pettersson

People with type 2 diabetes are at increased risk of Alzheimer’s disease and other cognitive problems. A new study led by Umeå University, Sweden, shows that the reason may be that people with type 2 diabetes have more difficulty getting rid of a protein that may cause the disease.

“The results may be important for further research into possible treatments to counteract the risk of people with type 2 diabetes being affected by Alzheimer’s,” says Olov Rolandsson, senior professor at the Department of Public Health and Clinical Medicine at Umeå University, research leader and first author of the study.

The researchers have studied two substances called beta-amyloids, which are among the most important components of the plaques found in the brains of people with Alzheimer’s disease.

The researchers measured the concentrations in the blood of the beta-amyloids Aβ1-40 and Aβ1-42 and of an enzyme that breaks down the beta-amyloids in a test group with type 2 diabetes and in a healthy control group. The two groups were given an infusion of glucose for four hours, which induced acute hyperglycaemia, i.e., high blood sugar levels after which repeated samples were taken from the subjects.

Immediately after the sugar solution was infused, the groups had similar values. Soon, beta-amyloid values fell sharply in the control group, while the values of the amyloid-degrading enzyme rose. Among the group with type 2 diabetes, there were no changes, i.e., beta-amyloid levels did not decrease, nor did an increase in the enzyme that breaks down amyloid. 

The results indicate that the body in people with type 2 diabetes does not have the same ability as in healthy people to take care of beta-amyloid, which could increase the risk that it is then stored in the brain and causes cognitive diseases such as Alzheimer’s.

“More research is needed to confirm the results of this limited study. Hopefully, it can also lead to new treatments in the long term. But the findings underline the importance of preventing type 2 diabetes as far as possible and that people who do have it should avoid having episodes of high blood sugar,” says Olov Rolandsson.

The study was conducted on ten people with type 2 diabetes and eleven people without diabetes in the control group. The participants were aged 66–72 years.

People with type 2 diabetes are at increased risk of Alzheimer’s disease and other cognitive problems. A new study led by Umeå University, Sweden, shows that the reason may be that people with type 2 diabetes have more difficulty getting rid of a protein that may cause the disease.

“The results may be important for further research into possible treatments to counteract the risk of people with type 2 diabetes being affected by Alzheimer’s,” says Olov Rolandsson, senior professor at the Department of Public Health and Clinical Medicine at Umeå University, research leader and first author of the study.

The substances that the researchers have studied are two so-called beta-amyloids, which are among the most important components of the plaques found in the brains of people with Alzheimer’s disease.

The researchers measured the concentrations in the blood of the beta-amyloids Aβ1-40 and Aβ1-42 as well as of an enzyme that breaks down the beta-amyloids in a test group with type 2 diabetes and in a healthy control group. The two groups were given infusion of glucose for four hours, which induced acute hyperglycaemia, i.e. high blood sugar levels, after which repeated samples were taken from the subjects.

Immediately after the infusion of the sugar solution, the groups had similar values. Soon, the values of beta-amyloids fell sharply in the control group, while the values of the amyloid-degrading enzyme rose. Among the group with type 2 diabetes, there were no changes, i.e. the levels of beta-amyloid did not decrease, nor did there be an increase in the enzyme that breaks down amyloid. 

The results indicate that the body in people with type 2 diabetes does not have the same ability as in healthy people to take care of beta-amyloid, which could increase the risk that it is then stored in the brain and causes cognitive diseases such as Alzheimer’s.

“More research is needed to confirm the results of this limited study. Hopefully, in the long term, it can also lead to new treatments. But the findings underline the importance of preventing type 2 diabetes as far as possible and that people who do have it should avoid having episodes of high blood sugar,” says Olov Rolandsson.

The study was conducted on ten people with type 2 diabetes and eleven people without diabetes in the control group. The participants were aged 66–72 years.

People with type 2 diabetes are at increased risk of Alzheimer’s disease and other cognitive problems. A new study led by Umeå University, Sweden, shows that the reason may be that people with type 2 diabetes have more difficulty getting rid of a protein that may cause the disease.

“The results may be important for further research into possible treatments to counteract the risk of people with type 2 diabetes being affected by Alzheimer’s,” says Olov Rolandsson, senior professor at the Department of Public Health and Clinical Medicine at Umeå University, research leader and first author of the study.

The substances that the researchers have studied are two so-called beta-amyloids, which are among the most important components of the plaques found in the brains of people with Alzheimer’s disease.

The researchers measured the concentrations in the blood of the beta-amyloids Aβ1-40 and Aβ1-42 as well as of an enzyme that breaks down the beta-amyloids in a test group with type 2 diabetes and in a healthy control group. The two groups were given infusion of glucose for four hours, which induced acute hyperglycaemia, i.e. high blood sugar levels, after which repeated samples were taken from the subjects.

Immediately after the infusion of the sugar solution, the groups had similar values. Soon, the values of beta-amyloids fell sharply in the control group, while the values of the amyloid-degrading enzyme rose. Among the group with type 2 diabetes, there were no changes, i.e. the levels of beta-amyloid did not decrease, nor did there be an increase in the enzyme that breaks down amyloid.

The results indicate that the body in people with type 2 diabetes does not have the same ability as in healthy people to take care of beta-amyloid, which could increase the risk that it is then stored in the brain and causes cognitive diseases such as Alzheimer’s.

“More research is needed to confirm the results of this limited study. Hopefully, in the long term, it can also lead to new treatments. But the findings underline the importance of preventing type 2 diabetes as far as possible and that people who do have it should avoid having episodes of high blood sugar,” says Olov Rolandsson.

The study was conducted on ten people with type 2 diabetes and eleven people without diabetes in the control group. The participants were aged 66–72 years.

Posted on Autism

Are food quality issues impacting the higher rates of Autism and ADHD in children in the developed world?

Percentage distribution of American children receiving SPED services by category, 2006 and 2021

U.S. SPED Caseload Percentages By Category, 2006 and 2021 CREDIT Dr. Raquel Crider

In a recent publication released by PubMed, American scientists led by Dr. Dufault at the Food Ingredient and Health Research Institute reported alarming increases in the numbers of children requiring special education services. While student enrollment in US schools remained stable from 2006 to 2021, the percentage of children receiving special education services increased by 10.4%. Among children with autism, the percentage receiving services tripled, jumping from 4% to 11%. Additionally, the caseload percentages for children with developmental delay quadrupled, increasing from 1% to 4%. Children qualifying for special education services under the category of other health impairments, which includes ADHD, jumped from 10% to 16%.

Dr. Dufault’s research team conducted a literature review to identify the epigenetic factors linked to the development of autism and ADHD. Over the past decade, numerous clinical trial data have suggested that dietary exposure to heavy metals and poor nutrition are the primary epigenetic factors that affect gene behavior and the inheritance of autism and/or ADHD in children. The prenatal consumption of ultra-processed foods has been shown to result in poor nutrition and exposure to heavy metals, which can adversely impact infant gene behavior both before and after birth.

The field of research that examines how dietary factors impact gene expression is called nutritional epigenetics. Dr. Dufault has been leading research in this area since 2005. During her time at the Food and Drug Administration, she was the first to identify the issue of inorganic mercury residues in high fructose corn syrup.

There is an ongoing issue with heavy metal residues in the food supply. In 2021, the US Congress released two reports addressing this problem in baby foods. The first report, issued on February 4, 2021, revealed that baby foods contain dangerous levels of arsenic, lead, cadmium, and mercury. The second report, issued on September 29, 2021, confirmed that manufacturers have disclosed new information showing even more baby foods with dangerous levels of heavy metals. These heavy metal exposures may exacerbate the development of autism and ADHD.

Posted on Exercise, Multiple Sclerosis

“Cognitive processing speed can be improved in individuals with multiple sclerosis through walking.”

Promising results support the need for large-scale randomized controlled trials of remote aerobic exercise training in individuals with MS-related cognitive impairment.

Promising results support development of large-scale randomized controlled trial of remote aerobic exercise training in individuals with MS-related cognitive impairment

“Preliminary research funded by the Kessler Foundation demonstrated that remote aerobic walking exercise training could be a successful method for improving cognitive processing speed impairment in people with multiple sclerosis (MS) who are fully ambulatory. The results from this single-blind randomized control trial provide support for designing a larger randomized, controlled trial involving a larger sample of people with MS.”

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Link: https://www.sciencedirect.com/science/article/abs/pii/S2211034823002134?via%3Dihub

The research team studied a group of 25 fully ambulatory individuals with MS who were initially screened for cognitive processing speed deficits; 19 of them completed the study as required. The researchers used the Symbol Digit Modalities Test (SDMT), a commonly used neuropsychological test to assess information processing speed in people with MS, and the California Verbal Learning Test (CVLT-II), a widely used test for verbal learning and memory. Assessments were carried out at the beginning of the study and after 16 weeks.

Participants were randomly assigned to either 16 weeks of remotely delivered and supported aerobic walking exercise training (intervention condition) or 16 weeks of remotely delivered and supported stretching and range-of-motion activities (control condition). They were given wearable fitness trackers and had weekly video consultations with an exercise specialist to ensure they were using the proper technique, following safety measures, and adhering to the prescribed exercise regimen.

The study’s results were promising. Participants who were randomly assigned to the intervention condition showed significant improvements in their SDMT scores after the 16-week study period compared to participants who were assigned to the stretching condition. This indicates that the remotely delivered aerobic walking exercise training positively impacted their cognitive processing speed. Additionally, the study found that participants had a high adherence rate to the exercise program, completing an average of 80% of the prescribed sessions.

“These findings are very important because cognitive processing speed impairment is a common symptom of MS, affecting up to 70% of patients. This impairment is associated with reduced quality of life, increased unemployment, and decreased social functioning. With limited effective treatments available, this study shows promise for individuals dealing with this disabling symptom.”

The remote delivery and support of the aerobic walking exercise training program have significant implications for improving the accessibility and convenience of care for individuals with MS. Many patients encounter obstacles when trying to attend in-person exercise programs, such as transportation issues or financial constraints. This study shows that exercise programs delivered remotely can be equally effective as traditional in-person interventions, offering a more inclusive solution for people with MS.

The researchers are hopeful about the potential applications of their findings. Lead author Dr. Sandroff, a senior research scientist in the Center for Neuropsychology and Neuroscience Research, stated, “Our study demonstrates that remote aerobic walking exercise training is not only feasible but may also be effective in treating cognitive processing speed impairment in individuals with MS.” The team expects that these findings will inspire the development of more accessible, convenient, and widespread exercise interventions, ultimately leading to an improved quality of life for those affected by this challenging disease.