A Gut Feeling About Fibromyalgia

By Pat Anson, PNN Editor

Over the years there’s been a lot of speculation about what causes fibromyalgia – everything from gluten and genetics to childhood trauma, spinal fractures and a weakened immune system.

About 5 million Americans suffer from fibromyalgia, a poorly understood disorder characterized by deep tissue pain, fatigue, mood swings and insomnia. It can take years for a patient to be diagnosed and treatments are often ineffective – in part because of uncertainty about what actually causes fibromyalgia.

For the first time, researchers at McGill University Health Centre in Montreal have found an association between gut bacteria and fibromyalgia. It’s not clear whether the microbes cause fibromyalgia or if they are a symptom, but the discovery opens the door to new forms of treatment and diagnosis. The findings are being reported in the journal Pain.

"We found that fibromyalgia and the symptoms of fibromyalgia — pain, fatigue and cognitive difficulties — contribute more than any of the other factors to the variations we see in the microbiomes of those with the disease,” said lead author Amir Minerbi, MD, of the Alan Edwards Pain Management Unit at McGill University Health Centre. 

“We also saw that the severity of a patient's symptoms was directly correlated with an increased presence or a more pronounced absence of certain bacteria - something which has never been reported before."

bigstock-Woman-Suffering-From-Stomach-A-64913737.jpg

Minerbi and his colleagues enrolled 156 women in their study – about half had fibromyalgia and the rest were a healthy control group. Participants were interviewed and gave stool, blood, saliva and urine samples, which were then compared.

Researchers found that the two groups had strikingly different types and amounts of gut bacteria. Nineteen different species of bacteria were found in either greater or lesser quantities in the gut microbiomes of fibromyalgia patients than in the healthy control group.

204022.jpg

For example, Faecalibacterium prausnitzii, one of the most abundant and well-studied bacteria in the human gut, was found to be depleted in fibromyalgia patients. It is believed to block pain and inflammation in the intestines.

Other bacteria associated with irritable bowel syndrome, chronic fatigue syndrome and interstitial cystitis were found to be abundant in the fibromyalgia patients, but not in the healthy control group.  

The bacterial differences don’t appear to be related to diets, lifestyles or genetics, since some of the healthy participants lived in the same house as the fibromyalgia patients or were their parents, offspring or siblings.

"We used a range of techniques, including Artificial Intelligence, to confirm that the changes we saw in the microbiomes of fibromyalgia patients were not caused by factors such as diet, medication, physical activity, age, and so on, which are known to affect the microbiome," says Minerbi.

Researchers say it's not clear whether the changes in gut bacteria seen in fibromyalgia patients are simply markers of the disease or whether they play a role in causing it. Because fibromyalgia involves a cluster of symptoms, the next step will be to investigate whether there are similar changes in the gut microbiome of patients with other types of chronic pain, such as back pain, headaches and neuropathic pain.

“This is the first evidence, at least in humans, that the microbiome could have an effect on diffuse pain, and we really need new ways to look at chronic pain." said senior author Yoram Shir, MD, Director of the Alan Edwards Pain Management Unit

If their findings are confirmed, researchers think their discovery could speed up the process of diagnosing fibromyalgia.

"By using machine learning, our computer was able to make a diagnosis of fibromyalgia, based only on the composition of the microbiome, with an accuracy of 87 per cent. As we build on this first discovery with more research, we hope to improve upon this accuracy, potentially creating a step-change in diagnosis," says Emmanuel Gonzalez, PhD, Canadian Center for Computational Genomics and the Department of Human Genetics at McGill University.

Several previous studies have suggested an association between diet and fibromyalgia. Donna Gregory Burch says her fibromyalgia symptoms improved when she went on a gluten-free diet. Studies show that consuming food additives such as monosodium glutamate (MSG) can worsen symptoms, while foods rich in Vitamin D can help reduce joint and muscle pain.

Rats, Depression and Chronic Pain

By Pat Anson, Editor

An unusual study involving rats, depression and chronic pain is making headlines – the latest in a long line of flawed research studies being used to debunk the effectiveness of opioid pain medication.

“NIH study suggests opioid therapy not effective against chronic pain,” is the headline in UPI.

“Pain-induced changes in the brain explain the limited effectiveness of opioid therapy,” is how the Tech Explorist put it.

At issue is a small study by the National Institutes of Health (NIH) and McGill University in Montreal on pain-induced changes in 17 laboratory rats. That's right, 17 rats. The study findings, published in the journal Pain, concluded that chronic pain reduced the number of opioid receptors – the molecules that opioids bind to -- in the rats’ brains. In theory at least, that would make the rats less responsive to opioid pain medication.

Note that the research did not include any people, the rats were not given any opioids, and the effectiveness of opioids wasn't even measured in the rats. But that didn’t stop the NIH from drawing some sweeping conclusions.

mouse-3194768_640.jpg

“These results provide insights into why we see limited effectiveness of opioid therapy in chronic pain and the mechanism of the depression that may accompany it,” said David Shurtleff, PhD, acting director at the National Center for Complementary and Integrative Health (NCCIH).

“These basic research findings support NIH’s efforts to better understand chronic pain and comorbid symptoms and to develop better ways to help chronic pain patients effectively manage their pain.”

McGill University was more cautious, saying further studies were needed in humans to confirm the study findings.

“Although the study… was conducted in rats, and the results of animal studies may not be directly applicable to people, the findings provide new insights into how the brain may respond to pain and opioids,” a McGill press release states. “These findings, if confirmed in people, will enhance the understanding of the impact of chronic pain on the brain, its relation to depression, and the effects of opioids.”

Researchers have many theories about the origins and treatment of chronic pain, but conducting tests on humans to prove them is problematic. Laboratory animals are often used as an imperfect substitute.

In the NIH/McGill study, 17 rats had brain surgeries to produce a nerve injury that causes chronic pain, while another group of rats had sham surgeries (a similar procedure that did not cause chronic pain). Three months later, PET scan imaging showed opioid receptors had decreased in multiple regions of the brain in the nerve-injured rats, but no changes occurred in the sham-surgery rats.

These results suggest that pain itself, not treatment or pre-existing trauma, altered the brain’s opioid system. Other tests showed a weaker link between chronic pain and depression in the nerve-injured rats.

How did researchers determine the rats were depressed? 

When given a choice, healthy rats will normally drink water sweetened with sugar rather than plain water. But animals with a decreased ability to experience pleasure, a recognized symptom of depression, may not. The rats in the study with chronic pain showed a decreased preference for sugar water over plain water, while rats in the sham group still showed a preference for sweetened water. This, the researchers believe, was enough evidence to conclude the nerve-injured rates were depressed.

“It’s well known that there’s a link between chronic pain and depression,” explained co-author M. Catherine Bushnell, PhD, scientific director of NCCIH’s Division of Intramural Research.  “The results of this study indicate that pain-induced changes in the brain’s opioid system may play a role in this association. Animals with the greatest decrease in opioid receptor availability showed the greatest increase in depression-like symptoms after experiencing chronic pain.”

While intriguing, the results of this rat study are far from definitive and do not prove that opioids are an ineffective treatment for chronic pain in people. What they do show is that we need more and better research about opioids and chronic pain, not more misleading headlines and statements from the NIH.

Chronic Pain Changes Our Immune Systems

By Pat Anson, Editor

Scientists already know that chronic pain can change the way our brains work, but now there is new evidence that pain may also make lasting changes in our immune systems.

In studies on laboratory rats, researchers at McGill University in Montreal found that chronic pain alters the way genes work in the immune system. The discovery may help explain why pain can persist long after the initial injury.

"We found that chronic pain changes the way DNA is marked not only in the brain but also in T cells, a type of white blood cell essential for immunity,” said Moshe Szyf, a professor in the Faculty of Medicine at McGill. "Our findings highlight the devastating impact of chronic pain on other important parts of the body such as the immune system."

McGill researchers examined DNA from the brains and white blood cells of rats nine months after a nerve injury. They found a “stunning” number of changes in DNA methylation – which regulates how genes function. Chronic pain appeared to reprogram how the genes work.

"We were surprised by the sheer number of genes that were marked by the chronic pain -- hundreds to thousands of different genes were changed," adds Szyf. "We can now consider the implications that chronic pain might have on other systems in the body that we don't normally associate with pain."

Many of the genes that were altered are associated with depression, anxiety, and loss of cognition, which are some of the negative side effects of chronic pain.  The findings could open new avenues to diagnosing and treating chronic pain in humans, as some of the genes affected by chronic pain could represent new targets for pain medications.

“These findings reveal potential new avenues for the development of novel therapeutics directed at either the molecular regulation of methylation or at key genes or pathways dysregulated in chronic pain,” the study found.  “This work also provides a possible mechanistic explanation for commonly observed comorbidities observed in chronic pain (i.e anxiety, depression). Finally, the sheer magnitude of the impact of chronic pain, particularly in the prefrontal cortex, illustrates the profound impact that living with chronic pain exerts on an individual.”

The McGill study is published in the journal Scientific Reports.

A recent study at Northwestern University found that chronic pain “rewires” a part of the brain that controls whether we feel happy or sad.  Researchers found that a group of neurons thought to be responsible for negative emotions became hyper-excitable within days of an injury that triggers chronic pain.