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New Study Explores Genetic Connection of Migraines

The nauseating, often debilitating, headaches affect 15-20 percent of adults in developed countries, yet they remain stubbornly hard to explain. Scientists know that migraines tend to run in families but aren’t sure exactly how. A new study published in the journal Neuron shows why some families are susceptible to migraines and how genetics may influence the type of migraine they get.

“For a long time, we have been wondering why common disease (like migraines) aggregates in families,” said Aarno Palotie of the Institute for Molecular Medicine in Finland and the Broad Institute of MIT and Harvard in Cambridge, Mass.

Previous migraine research identified two ways migraines might run in families. Linkage studies, which track sections of chromosomes passed down from parent to child, identified three genes (CACNA1A, ATP1A2 and SCN1A) associated to hemiplegic migraine, a severe form of migraine that induces stroke-like symptoms. These genes fall under a Mendelian inheritance model, meaning the two copies of a gene a child inherits from his or her parents determine a trait or disease. Sickle cell anemia could be thought of as Mendelian.

Another way migraines could run in families involves polygenic inheritance. If a trait is polygenic, that means that a group of genes collectively influence that characteristic. Like being dealt a bad hand in a card game, each common genetic variant may have only a small individual effect, but the collection of common variants builds up to influence the trait — or disease risk — a person inherits. Height is an example of a polygenic trait.

Palotie and his colleagues set out to find out whether a few, powerful Mendelian genes or a polygenic accumulation of common variants — or a combination of both — influenced how migraines are inherited in families.

First, the researchers developed a polygenic risk score to estimate the genetic burden of common variants. To do this, they gathered data from a previous genome-wide association study, which is a type of study that compares genomes of individuals and flags loci (locations on chromosomes) that differ in people with a disease. In all, hundreds (possibly even thousands) of loci linked to migraines were incorporated into the polygenic risk score.

Next, the researchers tested the influence of the polygenic risk score and the three known Mendelian migraine-linked genes within a large family study of migraine sufferers in Finland. The study included medical history and genetic data of 1,589 families (made up of 8,319 individuals) of known migraine sufferers. The family migraine cohort was compared against other large cohorts as a control, such as the FINRISK study that had 14,470 people total, including 1,101 people with migraine.

Result after result showed that the polygenic common variants were driving migraine risk more than the three Mendelian genes. If a person’s migraines started at an earlier age, if a person experienced more severe migraines, or if migraines ran in a person’s family, the data showed that it’s more likely that person had a greater genetic burden of common polygenic variants to blame.

“The strength of the common variants in these families surprised us,” said Palotie.

On the other hand, the three rare but powerful Mendelian genes linked to migraine didn’t seem to influence migraine risk as much as the researchers expected. Out of the large family study, researchers identified 45 families with hemiplegic migraine and sequenced their genes. Migraines in only four out of 45 families were driven by the rare Mendelian genes — more cases were driven by common variants.

“This really shows, in a very big sample set, that common variants are very important factors in aggregation of migraines in the family,” said Palotie.

Palotie believes more genome sequencing and larger studies will help researchers find both more common variants linked to migraines and more Mendelian variants.

“This is of special interest for drug development,” said Palotie. Even if Mendelian variants don’t drive the majority of migraine cases, scientists can research how these genes impact biological pathways responsible for migraine symptoms and potentially develop drugs to target those pathways.


Read this on Science Daily:  “New light on genetic foundation of migraines.” ScienceDaily. ScienceDaily, 3 May 2018. www.sciencedaily.com/releases/2018/05/180503142926.htm.

Customized resistance exercise may benefit women with Fibromyalgia

with proper support and individually adjusted exercises, female patients achieved considerable health improvements, according to research

Fibromyalgia and resistance exercise have often been considered an impossible combination. But with proper support and individually adjusted exercises, female patients achieved considerable health improvements, according to research carried out at Sahlgrenska Academy, Sweden.

“If the goal for these women is to improve their strength, then they shouldn’t be afraid to exercise, but they need to exercise the right way. It has long been said that they will only experience more pain as a result of resistance exercise, that it doesn’t work. But in fact, it does,” says Anette Larsson, whose dissertation was in physical therapy and who is an active physical therapist.

As part of her dissertation, she studied 130 women aged between 20-65 years with fibromyalgia, a disease in which nine of ten cases are women. It is characterized by widespread muscle pain and increased pain sensitivity, often combined with fatigue, reduced physical capacity and limitation of activities in daily life.

About half of the women in the study (67) were selected at random to undergo a program of person-centered, progressive resistance exercise led by a physical therapist. The other 63 women comprised the control group and underwent a more traditional therapy program with relaxation exercises. The training and exercises lasted for fifteen weeks and were held twice a week.

“The women who did resistance exercise began at very light weights, which were determined individually for each participant because they have highly varying levels of strength. We began at 40 percent of the max and then remained that level for three to four weeks before increasing to 60 percent,” explains Anette Larsson.

More than six of ten women were able to reach a level of exercise at 80 percent of their maximum strength. One of the ten was at 60 percent; the others were below that figure. Five individuals chose to stop the training due to increased pain. The group as a whole had 71 percent attendance at the exercise sessions.

“On a group level, the improvements were significant for essentially everything we measured. The women felt better, gained muscle strength, had less pain, better pain tolerance, better health-related quality of life and less limitation of activities. Some of the women did not manage the exercise and became worse, which is also an important part of the findings,” says Anette Larsson.

In the control group, the improvements were not as significant, but even there, hand and arm strength improved. The relaxation exercises probably led to reduced muscle tension in the arms and shoulders, which in turn allowed the participants to develop more strength.

The findings for the women in the resistance exercise group are affected by several factors, including the degree of pain and fear of movement before and during the exercise period. Progress for the group as a whole can largely be attributed to the person-centered approach, with individually adjusted exercises and loads and support of a physical therapist, according to Anette Larsson.

“An interview study we conducted shows clearly that the women need support to be able to choose the right exercises and the right loads; they also need help when pain increases. This requires, quite simply, support from someone who knows their disease, preferably a physical therapist.”

Title: Muscle strength and resistance exercise in women with fibromyalgia — a person-centered approach; http://hdl.handle.net/2077/55397

Read this article on Science Daily:

University of Gothenburg. “Customized resistance exercise a factor for success with fibromyalgia.” ScienceDaily. ScienceDaily, 7 June 2018. www.sciencedaily.com/releases/2018/06/180607120709.htm.

At Summit Pain Alliance we provide individualized pain management for a pain-free life. For more information and to schedule an appointment call (707) 623-9803.

Physical therapy benefits low-back pain patients

Patients with low-back pain are better off seeing a physical therapist first, according to a study of 150,000 insurance claims.

The study, published in Health Services Research, found that those who saw a physical therapist at the first point of care had an 89 percent lower probability of receiving an opioid prescription, a 28 percent lower probability of having advanced imaging services, and a 15 percent lower probability of an emergency department visit — but a 19 percent higher probability of hospitalization.

The authors noted that a higher probability of hospitalization is not necessarily a bad outcome if physical therapists are appropriately referring patients to specialized care when low back pain does not resolve by addressing potential musculoskeletal causes first.

These patients also had significantly lower out-of-pocket costs.

“Given our findings in light of the national opioid crisis, state policymakers, insurers, and providers may want to review current policies and reduce barriers to early and frequent access to physical therapists as well as to educate patients about the potential benefits of seeing a physical therapist first,” said lead author Dr. Bianca Frogner, associate professor of family medicine and director of the University of Washington Center for Health Workforce Studies.

Frogner said individuals in all 50 states have the right to seek some level of care from a physical therapist without seeking a physician referral, however, many do not take advantage of this option. She said this may be because some insurance companies have further requirements for payment.

About 80 percent of adults experience back pain at some point during their lifetime, according to the National Institutes of Health.

Currently, patients with low-back pain are given painkillers, x rays and, in some cases, told to rest, said Frogner. She said said seeing a physical therapist first and given exercise is a more evidence-based approach.

Using an insurance claims dataset provided by the Health Care Cost Institute, the researchers reviewed five years of data of patients newly diagnosed with low back pain who had received no treatment in the past six months. The claims were based in six states: Washington, Wyoming, Alaska, Montana, Idaho and Oregon.

The research involved the UW School of Medicine in Seattle and The George Washington University in Washington, D.C.

“This study shows the importance of interprofessional collaboration when studying complex problems such as low-back pain. We found important relationships among physical therapy intervention, utilization, and cost of services and the effect on opioid prescriptions,” said Dr. Ken Harwood, lead investigator for The George Washington University.

Story Source: Read this article on Science Daily: University of Washington Health Sciences/UW Medicine. “Early physical therapy benefits low-back pain patients: Analysis of 150k claims shows health, cost upsides.” ScienceDaily. ScienceDaily, 22 May 2018. www.sciencedaily.com/releases/2018/05/180522225553.htm.

Happy Clinical Trials Day

At Summit Pain Alliance we are proud to take part in the evolution of medical technology. We are constantly working to make our solutions more effective for our patients, with several ongoing clinical trials and many more to come we can do just that. Our highly trained Clinical Research Team will make sure every trial is conducted with the highest level of quality. Visit our Clinical Trials section to learn more, and contact us for information to discover how to become a participant.

The Clinical Trials Back Story

James Lind’s experiment with citrus fruit was one of the first reported clinical trials in medicine

May 1747. The HMS Salisbury of Britain’s Royal Navy fleet patrols the English Channel at a time when scurvy is thought to have killed more British seamen than French and Spanish arms. Aboard this ship, surgeon mate James Lind, a pioneer of naval hygiene, conducts what many refer to as the first clinical trial.

Acting on a hunch that scurvy was caused by putrefaction of the body that could be cured through the introduction of acids, Lind recruited 12 men for his “fair test.” (Ed: Historians are at odds regarding whether Lind secured Institutional Review Board approval before proceeding with subject recruitment, but largely agree his Informed Consent process did not measure up to modern standards.)

From The James Lind Library: Without stating what method of allocation he used, Lind allocated two men to each of six James Lind's experiment with citrus fruit was one of the first reported clinical trials in medicinedifferent daily treatments for a period of fourteen days. The six treatments were: 1.1 litres of cider; twenty-five millilitres of elixir vitriol (dilute sulphuric acid); 18 millilitres of vinegar three times throughout the day before meals; half a pint of sea water; two oranges and one lemon continued for six days only (when the supply was exhausted); and a medicinal paste made up of garlic, mustard seed, dried radish root and gum myrrh. (Ed: The existence accountability logs is yet another area of disagreement among historians, but many agree that Lind’s Essential Documents binder might have settled at the bottom of the English Channel.)

Those allocated citrus fruits experienced “the most sudden and good visible effects,” according to Lind’s report on the trial.

Though Lind, according to The James Lind Library, might have left his readers “confused about his recommendations” regarding the use of citrus in curing scurvy, he is “rightly recognized for having taken care to ‘compare like with like’, and the design of his trial may have inspired” and informed future clinical trial design.

*Additional information provided here: James Lind: The man who helped to cure scurvy with lemons 

Experiencing trauma as a child may contribute to a lifetime of pain

Experiencing trauma as a child may influence how much pain an individual feels in adulthood. Gaining insight about who feels more pain and why is important as issues like the opioid crisis continue to escalate.

Experiencing trauma as a child may influence how much pain an individual feels in adulthood, according to Penn State researchers. Gaining insight about who feels more pain and why is important as issues like the opioid crisis continue to escalate.

The researchers found that experiencing trauma or adversity in childhood or adolescence — such as abuse or loss of a parent — was linked with mood or sleep problems in adulthood, which in turn led to experiencing greater physical pain. But, the connection was weaker in those who felt more optimistic and in control of their lives.

“The participants who felt more optimistic or in control of their lives may have been better at waking up with pain but somehow managing not to let it ruin their day,” said Ambika Mathur, graduate student in biobehavioral health. “They may be feeling the same amount or intensity of pain, but they’ve taken control of and are optimistic about not letting the pain interfere with their day. They’re still performing their work or daily activities while doing their best to ignore the pain.”

The findings — recently published in the Journal of Behavioral Medicine — build on previous research that suggests a link between adult physical pain and early-in-life trauma or adversity, which can include abuse or neglect, major illness, financial issues, or loss of a parent, among others.

Jennifer Graham-Engeland, associate professor of biobehavioral health, said it’s important to learn more about the factors that influence pain, because while pain medications help a lot of people, they can also cause problems.

“Pain is the number one reason people seek health care in the United States,” Graham-Engeland said. “We know that a lot of people are seeking pain relief, and yet there are a lot of problems with some pain treatments, like the crisis surrounding opioids right now. We need more insight into pain and the phenomenon that can make pain both better or worse.”

For the current study, a diverse group of 265 participants who had all reported some form of adversity early in their lives answered questions about their early childhood or adolescent adversity, current mood, sleep disturbances, optimism, how in control of their lives they feel, and if they recently felt pain.

The researchers found that early childhood or adolescent adversity was strongly associated with more physical pain in adulthood, which could be explained by troubles with mood — which could include anger, depression or anxiety — or sleep.

“Basically what’s happening is mood and sleep disturbances are explaining the link between early life adversity and pain in adulthood,” Mathur said. “The findings suggest that early life trauma is leading to adults having more problems with mood and sleep, which in turn lead to them feeling more pain and feeling like pain is interfering with their day.”

The researchers also looked at how optimism or feeling in control could affect how much pain a person experiences. They found that while participants who showed these forms of resilience didn’t have as strong of a connection between trouble sleeping and pain interfering with their day, resilience didn’t affect the intensity of pain.

Jennifer Graham-Engeland said that while it’s too early to use the results in targeted interventions, the findings suggest important next steps.

“This study does build on a body of research showing a connection between early life adversity and pain, but also that some people can achieve resilience,” Jennifer Graham-Engeland said. “Some people can be relatively resilient to adverse effects in the longer term, while others have a harder time. So better understanding those resources that people are able to draw on was a reason for this work and I think needs to be further investigated.”

This work was supported by the National Institutes of Health’s National Institute of Aging.

Martin J. Sliwinski, Penn State; Joshua M. Smyth, Penn State; Danica C. Slavish, Penn State (now at University of North Texas); Richard B. Lipton, Albert Einstein College of Medicine; and Mindy J. Katz, Albert Einstein College of Medicine, also participated in this research.

Journal Reference:

  1. Ambika Mathur, Jennifer E. Graham-Engeland, Danica C. Slavish, Joshua M. Smyth, Richard B. Lipton, Mindy J. Katz, Martin J. Sliwinski. Recalled early life adversity and pain: the role of mood, sleep, optimism, and controlJournal of Behavioral Medicine, 2018; DOI: 10.1007/s10865-018-9917-8

Read this article on Science Daily: Penn State. “Adversity early in life linked with more physical pain in adulthood.” ScienceDaily. ScienceDaily, 9 May 2018. www.sciencedaily.com/releases/2018/05/180509104928.htm.

Study reveals that women feel pain differently

A female brain’s resident immune cells are more active in regions involved in pain processing relative to males, according to a recent study by Georgia State University researchers.

The study, published in the Journal of Neuroscience, found that when microglia, the brain’s resident immune cells, were blocked, female response to opioid pain medication improved and matched the levels of pain relief normally seen in males.

Women suffer from a higher incidence of chronic and inflammatory pain conditions such as fibromyalgia and osteoarthritis. While morphine continues to be one of the primary drugs used for the treatment of severe or chronic pain, it is often less effective in females.

“Indeed, both clinical and preclinical studies report that females require almost twice as much morphine as males to produce comparable pain relief,” said Hillary Doyle, graduate student in the Murphy Laboratory in the Neuroscience Institute of Georgia State. “Our research team examined a potential explanation for this phenomenon, the sex differences in brain microglia.”

In healthy individuals, microglia survey the brain, looking for signs of infection or pathogens. In the absence of pain, morphine interferes with normal body function and is viewed as a pathogen, activating the brain’s innate immune cells and causing the release of inflammatory chemicals such as cytokines.

To test how this sex difference affects morphine analgesia, Doyle gave male and female rats a drug that inhibits microglia activation.

“The results of the study have important implications for the treatment of pain, and suggests that microglia may be an important drug target to improve opioid pain relief in women,” said Dr. Anne Murphy, co-author on the study and associate professor in the Neuroscience Institute at Georgia State.

The research team’s finding that microglia are more active in brain regions involved in pain processing may contribute to why the incidence rates for various chronic pain syndromes are significantly higher in females than males.


Read this article on sciencedaily: Georgia State University. “Sex differences in brain activity alter pain therapies.” ScienceDaily. ScienceDaily, 3 March 2017. www.sciencedaily.com/releases/2017/03/170303091335.htm.

Dr. Yang’s Radio Interview Now Available for Listening

Listen to Dr. Yang of Summit Pain Alliance recent radio interview.

Dr. Yang was recently interviewed by Sonoma County’s Talking – KZST – Sonoma County’s Radio Station. In this interview Dr. Yang talks about the opioid crisis, medication addiction and new treatments for managing pain. Click on the interview below to listen to this informative discussion.


 

New study may hold hope for neuropathic pain patients

Imagine that the movement of a single hair on your arm causes severe pain. For patients with neuropathic pain — a chronic illness affecting 20 million people in the United States, with no effective treatment — this can be a daily reality.

Scientists from EMBL Rome have now identified a special population of nerve cells in the skin that are responsible for sensitivity to gentle touch. These are also the cells that cause severe pain in patients with neuropathic pain. The research team, led by EMBL group leader Paul Heppenstall, developed a light-sensitive chemical that selectively binds to this type of nerve cell. By first injecting the affected skin area with the chemical and then illuminating it with near-infrared light, the targeted nerve cells retract from the skin’s surface, leading to pain relief. Nature Communications publishes the results on 24 April 2018.

Strong curry

By clipping off the nerve endings with light, the gentle touch that can cause severe pain in neuropathic patients is no longer felt. “It’s like eating a strong curry, which burns the nerve endings in your mouth and desensitizes them for some time,” says Heppenstall. “The nice thing about our technique is that we can specifically target the small subgroup of neurons causing neuropathic pain.”

There are many different types of nerve cells in your skin, which make you feel specific sensations like vibration, cold, heat, or normal pain. These cells are not affected by the light treatment at all. The skin is only desensitized to the gentlest touch, like a breeze, tickling, or an insect crawling across your skin.

Illumination vs. drugs

Previous attempts to develop drugs to treat neuropathic pain have mostly focused on targeting single molecules. “We think however, that there’s not one single molecule responsible, there are many,” Heppenstall explains. “You might be able to succeed in blocking one or a couple, but others would take over the same function eventually. With our new illumination method, we avoid this problem altogether.”

Touch and pain were assessed by measuring reflexes in mice affected by neuropathic pain in their limbs. Affected mice will normally quickly withdraw their paw when it is gently touched. After the light therapy, however, they exhibited normal reflexes upon gentle touch. The effect of the therapy lasts for a few weeks, after which the nerve endings grow back and gentle touch causes pain again.

The team also investigated human skin tissue. The overall makeup of the tissue and the specifics of the neurons of interest appear to be similar, indicating that the method might be effective in managing neuropathic pain in humans. “In the end, our aim is to solve the problem of pain in both humans and animals,” says Heppenstall. “Of course, a lot of work needs to be done before we can do a similar study in people with neuropathic pain. That’s why we’re now actively looking for partners and are open for new collaborations to develop this method further, with the hope of one day using it in the clinic.”


Story Source:

Materials provided by European Molecular Biology Laboratory. Note: Content may be edited for style and length.

Read this article on sciencedaily.com: European Molecular Biology Laboratory. “Managing chronic pain with light: Scientists develop new method that uses light to manage neuropathic pain in mice.” ScienceDaily. ScienceDaily, 24 April 2018. www.sciencedaily.com/releases/2018/04/180424083904.htm.

Proper pain treatment may reduce depression and anxiety in migraine patients

In a study of 588 patients who attended an outpatient headache clinic, more frequent migraines were experienced by participants with symptoms of anxiety and depression. In the Headache study, poor sleep quality was also found to be an independent predictor of more severe depression and anxiety symptoms.

The study’s investigators noted that factors such as emotional distress and frequency of headache may influence each other through a common pathophysiological mechanism. For example, emotional responses have the potential to alter pain perception and modulation through certain signaling pathways.

“These findings potentially suggest that adequate medical treatment to decrease headache frequency may reduce the risk of depression and anxiety in migraine patients,” said Dr. Fu-Chi Yang, corresponding author of the study and an investigator in the Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taiwan.


Read this article on Science Daily: “Anxiety and depression linked to migraines.” ScienceDaily. ScienceDaily, 18 October 2017. www.sciencedaily.com/releases/2017/10/171018090209.htm.