“All disease begins in the gut”–Hippocrates
It hopefully goes without saying (but I’ll say it anyway), that pain is a very complex issue. Thankfully, through the work of people such as Louis Gifford, Mick Thacker, Lorimer Moseley, and David Butler, among others, our understanding of pain and how to address it with our patients has greatly improved. “Explain pain,” or “therapeutic neuroscience education” has become a popular intervention for the treatment of patients with persistent pain and hypersensitive nervous systems. While much of the pain neuroscience education has focused on the “no brain, no pain” approach, Gifford and Thacker have proposed the Mature Organism Model (MOM), which takes into account the entire individual self, not just the brain, as being involved in a pain experience. This is a challenge to the emerging trend of practitioners becoming what Thacker refers to as “brain-bound.”
We know that especially in the human body, all systems are interconnected and it’s incomplete if we consider just one system without its effect on the others. The concept of regional interdependence highlights this for us. We can’t look at a shoulder problem, for example, without considering the effects from the cervical and thoracic spine, ribs, and even the low back and lower extremities with athletic populations. In the same light, we no longer look at pain as simply related to tissue injury. But I don’t think we should let the pendulum swing too far the other way and say that pain is only a construct by the brain. It is more likely a complex networking of multiple systems including the nervous system, musculoskeletal system, endocrine system, immune system (and probably more); all interacting with our attitudes, beliefs, memories, motivations, and our environment.
“Whenever a complex issue is raised, I always answer the question ‘why’ with the response, “part of the reason is,” because there is never just one answer”–Sanjay Bakshi
It is in this light, where emerging research into the gut micobiome may provide insight as to how our gastrointestinal system may also play a role in many individuals suffering with persistent pain. As we will see, the bacteria in our gut has a large influence on our immune system as well as direct connections to the endocrine system and even the brain.
So what is the microbiome?
The microbiome is composed mostly of bacteria that resides in our small intestine. Some neurologists are now calling it the “second brain” due to its numerous connections to the nervous system. 70% of our immune system actually lies within our gastrointestinal system and there are more neurons in our small intestine than within our spinal cord! The vagus nerve (CN X) is the primary conduit between our bacteria and the central nervous system. This communication is also now believed to be bi-directional. Not only can thoughts or feelings give us “butterflies” in our stomach when we’re nervous or anxious, for example, but bacteria in the gut can release chemical messengers similar to hormones that travel along the vagus nerve to the brain. In fact, almost 90% of our serotonin, regarded as one of our “happy chemicals,” is actually manufactured by the bacteria in your gut, not in the brain.
Although our microbiome contains both “good” and “bad” bacteria, it is the balance between the two that has been shown to be important, as well as the diversity among the baceteria present in the gut. There are over 400 species of microbes living within our small intestines weighing over 15 pounds. The microbiome is so important that in 2008, the Human Microbiome Project was started by the NIH as an extension to the Human Genome Project.
Even though we may get those “gut” feelings, our small intestines do not contain nociceptors. However, we can “feel” when there may be a problem, although we don’t always know that the source might be coming from within. For example, food sensitivities/reactions and other gastrointestinal disturbances have been linked to:
- asthma and allergies
- autoimmune disorders
- skin conditions
- arthritis
- atherosclerosis and other cardiovascular diseases
- neurodegenerative diseases such as dementia
- mood disorders
- ADD/ADHD
- narcolepsy
- addiction
- migraines
- kidney problems
That’s quite a list!
The microbiome and pain
If pain is an output based on the perception of a threat, and our perceptions produce our reality, then our perceptions clearly play an enormous role in how we experience pain. Can we control our perceptions? As it turns out, there just might be: meditation, cognitive-behavioral therapy, and graded exposure, to name a few. But what we put in our mouths may also affect our perceptions.
“The microbiome affects our mood, libido, metabolism, immunity, and even our perception of the world and the clarity of our thoughts.”–Dr. David Perlmutter, author of Brain Maker
Researchers at UCLA published a study in 2013 in the journal Gastroenterologylooking at fMRI responses in groups of people being shown threatening images. Although it was a small study, with only thirty-six women participating, the results are nonetheless intriguing. The women were divided into three groups: the first group consumed a probiotic yogurt 2x/day for 4 weeks; the second group ate a dairy product that looked like yogurt without any probiotics; and the third group was the control and was not instructed to eat anything specific at all. All thirty-six women underwent fMRI scans of their brains at the start of the study and then at the end. At the four-week mark, they were shown images designed to elicit an emotional response. The women who ate the yogurt with the prebiotics demonstrated reduced activity in the insula and somatosensory cortex compared to the other two groups which showed stable or increased activity. The researchers reasoned this to indicate that they exhibited less of an emotional reaction in response to the images compared to the other two groups.
Furthermore, when the fMRI was performed on the subjects when not viewing the images, the results showed in the group who at the probiotic yogurt, there was greater connectivity between the prefrontal cortex and regions of the brainstem associated with cognition. In the control group who didn’t eat any product, there was more connection to regions of the brain associated with emotion. The group who ate the dairy product without probiotics demonstrated results somewhere in the middle.
“The most significant factor related to the health and diversity of our microbiome is the food we eat”--Dr. Anthony Fasano
Can absolute conclusions be drawn from this yet? Not entirely, but it’s certainly interesting and likely only the first step to further inquiry and investigation.
Adriaan Louw, co-author of Therapeutic Neuroscience Education, likes to use the example of a large African lion following us around as a metaphor for chronic pain. If we’re sitting comfortably at home and a lion bursts into our room , we would have a very understandable stress reaction–increased adrenaline (along with hypervigilance), increased peripheral vasodilation, increased activity of our large muscles for “fight or flight” responses along with reduced activity to the smaller, postural muscles, reduced digestion, and faster and shallower breathing. Once the lion is captured or we’re able to get away, the system slowly returns to baseline.
However, in people with chronic, persistent pain, they have a metaphorical lion following them around all day, and their “fight-or-flight” responses remain continually elevated. Dr. Perlmutter points out that an imbalance between bacteria in our guts can interact with our immune system causing the release of inflammatory chemicals and stress hormones, kicking off our body’s natural stress response, even when we are not truly in a stressful situation.
For example, adrenaline, while a short-acting neurotransmitter, converts to cortisol. Cortisol has a normal diurnal pattern, with levels highest in the morning and slowly declining throughout the day. However, in people with chronic pain, cortisol levels are elevated and remain elevated, resulting in several undesirable effects including weight gain due to altered protein and fat metabolism, mood changes, and difficulty sleeping. It also can play a role in increasing the permeability of the gut lining, leading to increased inflammatory chemical production from immune cells. Peripheral nerves can become sensitive to adrenaline and cortisol, due to ion channel proliferation, so prolonged exposure increases their sensitivity to these chemicals. Any small immune response afterwards, which triggers an increase in adrenaline, can result in overly sensitive nervous system activity.
The catch is, our body is not able to distinguish an actual physical threat, like a lion bursting into your living room, from a mental stress like running late to an important meeting. So what happens when our brains think we are constantly under such stresses? Can these stress response occur as a result of what we eat? In a 2004 study published in the Journal of Physiology, Japanese researchers examined the effects of stress on mice that lacked a microbiome (“germ-free mice”). The mice overreacted, as it were, to stress. The good news is that this state could be reversed just by giving them the probiotic Bifidobacterium infantis.
“Although our body may not necessarily go into fight-or-flight mode with a pounding heart when it meets a substance or ingredient it doesn’t like, it most definitely will experience an immune response. And chronic immune activation and resulting inflammation from such encounters can lead to chronic disease, from heart and brain disease, depression, and dementia”–Dr. Perlmutter
The microbiome and the CNS
In 2012, researchers at Baylor College of Medicine and Texas Children’s Hospital found a strain of bacteria that secretes large amounts of GABA, an important neurotransmitter in the central nervous system. GABA is an inhibitory neurotransmitter that functions essentially to calm down the nervous system and return it to a more stable state. During nociception, fibers coming from the periphery synapse with an interneuron on the dorsal horn of the spinal cord. At this point, a decision is made–the interneuron is like bouncer at a club; it can either let the stimulus through or prevent it from entering. If the latter, the stimulus ends there, and no message to higher brain centers will take place, meaning no chance of interpretation and perception. The presence of GABA in the synaptic cleft will result in an inhibitory response.
So, in the previous example with the lion, after it’s is captured by animal control or you’re able to escape to safety, the sympathetic nervous system is able to settle back down in part due to the presence of GABA in the CNS. But what happens if your gut bacteria balance is off and less GABA is produced for availability within the CNS? Could this be one contributor to why people with chronic pain have trouble “turning off” their fight or flight responses even to non-threatening stimuli?
Another way in which our gut bacteria plays a role with our perception of pain may be in the link between chronic pain and depression. Are people with depression more likely to develop chronic pain or are people in chronic pain more likely to develop depression? I don’t know the answer. But what we do know is that depression is the leading cause of disability worldwide, impacting more than 350 million people. Prolonged cortisol exposure (as with people in chronic pain) has been linked to depression. Studies have shown that higher levels of systemic inflammation also increase the risk for developing depression and the higher the levels of the inflammatory markers, the worse the depression. One source of systemic inflammation can be due to food sensitivities or dysfunction of the microbiome.
A recent Oxford University study found that giving people prebiotics (food for good bacteria) resulted in positive psychological effects. When compared to placebo taken daily for three weeks, the individuals who took the prebiotic paid more attention to positive messages and less attention to negative information. Additionally, the same group also had lower levels of cortisol when measured in the morning, at a time when cortisol levels are supposed to be the highest.
“Let food be thy medicine, and medicine be thy food”
Retired NFL-great Tony Gonzalez writes in his book, The All-Pro Diet, about the foot pain that bothered him for the first half of his career, even years after surgery and rehab. At the time, he was eating a typical diet for a twenty-something: lots of fast food, processed foods, fried foods, and soda, and very low on fruits and veggies. Once becoming a vegan (not that I’m recommending that, either), his foot pain vanished. He didn’t have an explanation as to why that happened. And while we can’t yet determine an exact causal relationship between the two, it’s enough to imply a link.
So, where do we come in with all this? In an earlier post, I proposed a more pragmatic approach to nutritional counseling. Although there are always exceptions, in general, physical therapists do not have the requisite training to provide the level of information at the standard that is necessary for our patients. What we think we know about certain diets and nutrient amounts is not only constantly changing, but can also vary so much between individuals. However, I think there is a part we can play when it comes to our patients in chronic pain. As we know, pain is a very complex, multi-factorial phenomenon. Educating our patients appropriately on what we know about pain science in general is most certainly one piece.
By providing people with information regarding the impact of certain foods on the body (some of more common ones likely to produce sensitivities including gluten, dairy, nuts, and eggs), along with alternative food choices, we can help our patients make a more informed decision when it comes to their health. One thing we can recommend to our patients to help determine what foods they may be sensitive to is an elimination diet.
“Despite the multitude of currently available food allergy tests, the elimination diet still remains the gold standard for identifying food sensitivities”–Bryan Walsh
Where to start? The folks over at Precision Nutrition have some suggestions: A good elimination diet will remove gluten, dairy, soy, eggs, corn, pork, beef, chicken, beans/lentils, coffee, citrus fruits, nuts, and nightshade vegetables. That might sound like a lot, but it still leaves plenty of options for a relatively satisfying diet comprised primarily of rice, meat (turkey, fish, lamb), most fruit, and most types of vegetables. And according to Dr. Perlmutter, foods that can help improve the microbiome include prebiotics, probiotics, fermented foods, low-carb foods, gluten-free foods, and healthful fat. Some specifics include garlic, coffee, dandelion greens, kombucha, and fermented foods such as sauerkraut and kimchi.
With all this, as a rule of thumb, I will acknowledge to my patients that while in this arena I am by no means an expert, with the reading I have done, this is what the research seems to be showing. If they are interested, I will provide them with additional resources to set them on the path for their own individual discovery. When dealing with pain, this is only one piece of a complex puzzle, but as I’ve hopefully demonstrated, it’s one piece that when incorporated with others, starts to address one more system that appears to have a large influence over some of the others involved in the pain experience.
As always, thanks for reading. Comments and discussion welcome.
Cheers,
Resources:
Dr. David Perlmutter, MD. Brain Maker 2015
Interested in live cases where I apply this approach and integrate it with pain science, manual therapy, repeated motions, IASTM, with emphasis on patient education? Check out Modern Manual Therapy!
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