Total Recovery, page 12
“Isn’t that your car?” Paul pointed to her black BMW convertible, not 10 feet away from where she was standing.
A few weeks later, when Nicole went to the grocery store, the same thing happened again. She thought her car was not where she’d parked it. This time, when she started to panic, she took a deep breath and tried to stay calm. With all of her groceries, she walked back into the grocery store and turned around. “Let’s try this again,” she told herself.
This time, when she walked back out into the parking lot, she found her car but didn’t like what she saw. Her car had rolled out of its parking space and into another car. Apparently, she’d forgotten to set the brake. Nicole had been driving manual transmissions for 35 years and had never forgotten to set the brake before.
Nicole went back to Dr. Lisa the next day and said, “I don’t stagger anymore, and that’s great. But I can’t do anything else! When my memory is so bad I can’t remember how to park my car, how can I work? Will I even remember how to get to a client’s office?”
Dr. Lisa sent Nicole back to the neurologist, who requested that the extensive neuropsychological testing be redone to see if there was any improvement. The results showed no improvement, but she hadn’t gotten worse.
As the months wore on, the strain was almost too much for Nicole. She was not able to do some of the easiest, most basic things. On top of everything else, she felt she was letting Rick down. They had planned for him to retire the year she got sick, but, with Nicole unable to work, Rick had to keep working. And they didn’t know how long it would have to go on.
The situation was so discouraging that Nicole was crying all the time. Her confident business consultant persona was gone. She spent most of her days feeling worthless and defeated.
Seeing how miserable she was, everyone encouraged her to take antidepressants. She tried them for a month, but they didn’t help. Dr. Lisa asked her to see the therapist at the Kaplan Center for at least 6 weeks.
After meeting with Nicole a few times, the therapist canceled the rest of the sessions. “You’re not depressed,” she said. “You’re upset and pissed off about the horrible situation you’re in. Who wouldn’t be?”
MEETING NICOLE
At that point, Nicole was referred to me. Because of our biweekly meetings to discuss patients at the clinic, I was already aware of her case.
She had been diagnosed with and treated for Lyme with only a partial response to therapy. What were we missing? After reviewing the reports of the other physicians and taking Nicole’s history myself, I ran blood tests for heavy metals.
The first test came back negative. I explained to Nicole that if she did have heavy metal toxicity and the test was negative, the metals were not actively circulating in her blood. Another test would tell us if they were being harbored in her bones and tissue.
The results of the second test showed that Nicole had a significant amount of lead in her tissues. Lead, mercury, arsenic, and other heavy metals are ubiquitous in our environment, and there are many potential sources of poisoning. Heavy metals poison many enzyme systems in the body and can cause a number of illnesses, but they especially damage our nerves and brain.
Nicole had suffered from lead poisoning as a child after eating paint chips, but she was unsure whether she had ever been treated. That episode and decades of exposure to the fumes from leaded gasoline left me suspicious that heavy metals, festering in her tissues, were interfering with her recovery.
Treating the whole patient often requires careful decisions about which issues to address first. Despite the standard recommendations of the CDC in general, recent studies have shown that more than 20 percent of people with Lyme develop what the CDC calls post-treatment Lyme disease syndrome (PTLDS).2 In those people, Lyme persists after treatment, evading the standard course of antibiotics.3 Because of this, the duration and type of antibiotic treatment must be tailored to each patient. Many physicians believe that treatment for Lyme must continue until the patient has been symptom free for at least a month.
One of the concerns is that when patients develop PTLDS, it is because some unseen factor is suppressing their immune system, inhibiting their recovery. In Nicole’s case, I wondered if the elevated lead levels in her body were creating that effect. Lead poisoning could have been responsible for some of her symptoms, and it might also have been keeping her from recovering from Lyme.
The treatment for Nicole’s lead poisoning could be handled quickly with chelation therapy, which might relieve her symptoms, as well as improve her immune function, but we could not do it while she was taking antibiotics. So I took her off the antibiotics, treated her for lead poisoning with oral chelation therapy, then put her back on antibiotics for Lyme.
As the months went by, Nicole’s memory gradually began to come back. The shaking became more moderate. The area of numbness on her right side began to diminish as well, proving it had never been multiple sclerosis.
“If this had gone much further,” Nicole said, “I think I would’ve been in a wheelchair for life.”
After she finished the second course of antibiotics, I put her on Atacand, a blood pressure medication, and low-dose naltrexone to quell the inflammation. My research indicated that the inflammation in the brain caused by Lyme and Lyme-related diseases could not be reduced by antibiotics and antiparasitic medications alone.
I prescribed low-dose Naltrexone, a very versatile medication. It is used in emergency rooms to save the lives of patients who have overdosed on drugs. By counteracting the addictive high of morphine, heroin, and alcohol, it has also given substance abusers relief from their addictions. My research has shown that Naltrexone acts to reduce inflammation in the brain. That makes it useful in treating conditions such as fibromyalgia and Lyme-related diseases, where antibiotics alone do not result in total recovery.
THE PRACTICE OF PARTIAL RECOVERY
If it was already obvious in medical school that people were suffering from increasingly complicated conditions, it was even worse now. The patients we saw at the clinic had often seen 8 to 15 other physicians before coming to the center. It was not uncommon for them to have been evaluated and treated at some of our best medical centers such as Mayo Clinic and Johns Hopkins. We were still able to help most of the people who came to see us, but achieving total recovery was proving more elusive.
The underlying mechanism was still a mystery. And I knew that until we found the cause, we would never find a cure.
With our patients exhibiting such a wide array of symptoms, it was nearly impossible to see the connection. How were physical injuries, viral infections, nutritional deficits, hormonal imbalances, and emotional disorders related? What was the common denominator?
Again and again, my mind kept returning to the common occurrence of pain and depression in the same people. Some of the people who experienced chronic pain may already have been prone to mood disorders, of course. For others, the persistent physical misery of chronic pain may have given way to a feeling of despair. But even taking those two possibilities into account, the number of people who had both pain and depression was inexplicably high.
In the general population, approximately 16 percent will experience a major bout of depression in their lives, while 15 percent will experience chronic pain in any given year. Of those people, 65 percent will experience both at the same time.4
There was also a growing recognition that people who had both conditions together had a dramatically lower chance of recovery with our current treatments. The odds of recovering from a major bout of depression were 47 percent. If a patient had both pain and depression, the likelihood of recovery dropped precipitously to 9 percent.5
It was obvious what was happening, but why was it happening?
DIGGING DEEPER
Dr. José Apud and I often had long conversations, wondering what it was that brought our specialties—pain management and psychiatry—together so frequently. As new research would come out, we would pour over it in the study group, looking for clues that could explain the connection between these two conditions.
Judging by the deterioration I was seeing in the patients who arrived at my clinic, I was starting to suspect that both pain and depression were neurodegenerative. But I was spending hours reading medical journals, and none of the literature was talking about it.
It was slowly dawning on me that if I was determined to isolate the underlying mechanisms of these conditions, I was going to have to go deeper into neurophysiology than I’d expected. In medical school, I’d originally planned to become a neurologist. Now it looked like I was going to end up going down that road after all. Compiling all the latest studies on neuroinflammation in depression, I dug in, assuming I was going to have to put myself through a mini-master’s program in neurophysiology before I found anything that could help the patients with complicated conditions.
Months went by. Each time I found something of interest, I would take it to the group or discuss it with Dr. Apud, but I didn’t find anything too enlightening at first.
Late one night, I came across a paper by neurologist Michael J. Robinson and his colleagues at Eli Lilly, one of the largest pharmaceutical companies in the world. Examining pain and depression from a neurological point of view, he found they had more in common than the medical community had assumed. In fact, they shared much of the same neurophysiology. More exciting, however, were his arguments that these were both neuroinflammatory diseases.6
This was a breakthrough insight. I rushed the data to the study group, and we set to work, trying to grasp the implications. Two questions were foremost in my mind:
• If pain and depression shared a similar neurological base, were they two separate diseases or different manifestations of the same disease?
• And when they occurred together, what made them ignite a synergy, creating a condition that was more than the sum of its parts?
The idea that pain and depression were inflammatory diseases was a radically new concept. It would require a completely different approach than either physicians or psychiatrists had been using to evaluate and treat patients.
In 2009, we understood very little about the nature of inflammation in the central nervous system. The brain is considered “an immunologically privileged” organ. Our brains have their own unique immune systems. While the brain’s immune system can and does interact with the peripheral immune system, that interaction is limited and closely regulated.
The brain and spinal cord, which make up the central nervous system (CNS), are connected to every organ and limb by the peripheral nervous system. Because of its vital importance, the CNS is completely encased in bone. From the top of our skulls to the base our spines, it is shielded from external assaults. Deep inside, our brains are protected from contamination by the blood-brain barrier. As R. Douglas Fields explains in The Other Brain, “The cells forming the walls of blood vessels in the central nervous system are sealed together so tightly that cells and molecules in the bloodstream, which freely pass into tissue elsewhere in the body, are unable to cross into brain tissue.”7 It was widely assumed that because of this barrier, brain inflammation was rare, the result of extreme illnesses or violent injuries.
Curiously enough, the response of patients with hepatitis was raising questions about these assumptions. When they were treated with interferon, these patients consistently became clinically depressed.8 Since interferon is one of the molecules that causes inflammation in the body, researchers came to suspect that there was an undiscovered link between inflammation and depression.
In the last few years, as they began to investigate, they discovered that anxiety disorders and PTSD also accompanied elevated inflammatory molecules in the central nervous system. This led to the astonishing conclusion that depression, anxiety, and PTSD were all neuroinflammatory diseases in the brain.9
It is important to clarify what we mean when we talk about inflammation. There are many different types of inflammatory pathways in the body. When we call all of them “inflammation,” it’s like talking generally about “illness.” Physiologically, each type of inflammation is very different, engaging different types of cells and different parts of the immune system.
At the simplest level, inflammation associated with allergies is mediated by one pathway (IgE), food intolerances by another (IgG), and celiac disease by others (IgA and IgG anti-tTG). Bacterial infections cause inflammation by a completely different route (the activation of white cells), while biotoxic inflammation involves cytokines and interferon.
We may use an antibiotic to treat the inflammation from a bacterial infection, but the same antibiotic would be completely ineffective in treating an allergic response, just as the antihistamines or steroids we might use to treat an allergy would do little to combat bacteria.
What we’re just beginning to understand is that inflammation quickly gets complicated. Depending on how many cumulative traumas the body has endured, inflammation can spread like a brush fire. When it flares up in one pathway, it can ignite a secondary inflammatory response in peripheral pathways.
Inflammation has been a hot topic in medicine for the last 10 years. Within the integrative medical community, many chronic diseases are being seen as a consequence of chronic inflammation throughout the body. New studies are confirming neurodegeneration that is the result of sustained low-grade inflammatory states. There is speculation that central nervous system inflammation may be a precursor to all kinds of conditions, from autism to fibromyalgia to Alzheimer’s.10 It is even thought that inflammation in the spinal cord may be a mechanism for chronic pain.11
In 2009, Dr. Robinson and his team were among the early researchers to connect both pain and depression to inflammation in the brain. If they were right that pain and depression were neuroinflammatory diseases with a common origin, the real question was: What was causing and sustaining that inflammation?
FINDING THE CONNECTION
While I was mulling it over, I attended a seminar at the American Academy of Pain Management about inflammatory factors in the brain—interleukins, a group of signaling molecules that participate in the body’s immune responses, and the tiny cells that would change my whole way of thinking: microglia.
The more I read about microglia, the more I was convinced that they played an important role in the development of pain and depression.
Microglia act as the resident immune system of the central nervous system. If anything manages to slip past the blood-brain barrier, the microglia intervene. “Squeezing between tangles of dendrites and axons as they rush to kill the invader, microglia attack and devour any harmful organism.”12
In order to protect the brain, the microglia secrete inflammatory chemicals to create swelling that acts as a buffer, as they work to destroy the invaders. While this inflammatory counterattack is going on at the molecular level, the person enduring it begins to feel sick with fatigue, headaches, fevers, and achiness all over.
As I began to investigate microglia, I found dozens of articles in medical journals, each one linking microglial inflammation to a different stressor: physical injury, psychological trauma, loss of oxygen to the brain, bacterial infections, viral infections, environmental toxins—the list was long. Whenever the central nervous system was stressed, the microglia upregulated, responding the only way they knew how: by creating inflammation.
And suddenly I saw it.
When microglia are upregulated, they create widespread inflammation in the central nervous system. If they are turned on too often, they become hyperreactive, keeping the brain in a chronic state of inflammation.
In some people, the microglia remain activated for longer periods of time. We see evidence of this in teenagers who binge drink. Heavy alcohol consumption triggers the microglia. Researchers in one study confirmed that teenagers’ nervous systems were measurably inflamed, then checked their levels of inflammation at intervals to see when it subsided. (Inflammatory chemicals, Interleukin-6, TNF alpha, and Interleukin-1 beta are clear biomarkers for upregulation of microglia because they are produced by microglia in the brain.) After the teenagers stopped drinking, their microglia remained upregulated for a decade.13
What this study demonstrates is two very important concepts. The first is that the traumas we suffer have a cumulative effect. Every injury, every infection, every toxin, every physical trauma, every emotional blow generates the same reaction. Inside the brain, it triggers the microglia again and again and again.
The second realization is even more startling. There comes a point when the microglia have been activated in such a way that they remain upregulated, continuing to spew out inflammatory chemicals even though the trauma that originally caused them to become active is no longer present. That response can show up in any number of ways: chronic pain, depression, anxiety disorders, fibromyalgia, chronic headaches, and PTSD, to name a few. All of these and many other medical conditions are the manifestation of chronic microglia activation.
No matter how it shows up, any condition that is caused by the activation of microglia is just a variation on the theme. Genetic proclivities or the particular combination of cumulative assaults result in different manifestations, but at the physiological level, one single underlying process is taking place.
Now I had a target, a way of understanding inflammation in the central nervous system. My first goal was to identify everything that makes the microglia start setting fires in the brain. Treating those things would surely improve my patients’ conditions.
The second goal would be to understand how to turn off the microglia and return them to their non-inflammatory resting state once their job of protecting the brain from the original trauma was completed.
But the implications were even greater than that. Medicine was getting it all wrong. Chronic pain in all its forms—depression, PTSD, and a number of other neuropsychiatric conditions—were not distinct diseases but symptoms of an underlying neuroinflammatory disease. The cause of that inflammation was chronically upregulated microglia.
A few weeks later, when Nicole went to the grocery store, the same thing happened again. She thought her car was not where she’d parked it. This time, when she started to panic, she took a deep breath and tried to stay calm. With all of her groceries, she walked back into the grocery store and turned around. “Let’s try this again,” she told herself.
This time, when she walked back out into the parking lot, she found her car but didn’t like what she saw. Her car had rolled out of its parking space and into another car. Apparently, she’d forgotten to set the brake. Nicole had been driving manual transmissions for 35 years and had never forgotten to set the brake before.
Nicole went back to Dr. Lisa the next day and said, “I don’t stagger anymore, and that’s great. But I can’t do anything else! When my memory is so bad I can’t remember how to park my car, how can I work? Will I even remember how to get to a client’s office?”
Dr. Lisa sent Nicole back to the neurologist, who requested that the extensive neuropsychological testing be redone to see if there was any improvement. The results showed no improvement, but she hadn’t gotten worse.
As the months wore on, the strain was almost too much for Nicole. She was not able to do some of the easiest, most basic things. On top of everything else, she felt she was letting Rick down. They had planned for him to retire the year she got sick, but, with Nicole unable to work, Rick had to keep working. And they didn’t know how long it would have to go on.
The situation was so discouraging that Nicole was crying all the time. Her confident business consultant persona was gone. She spent most of her days feeling worthless and defeated.
Seeing how miserable she was, everyone encouraged her to take antidepressants. She tried them for a month, but they didn’t help. Dr. Lisa asked her to see the therapist at the Kaplan Center for at least 6 weeks.
After meeting with Nicole a few times, the therapist canceled the rest of the sessions. “You’re not depressed,” she said. “You’re upset and pissed off about the horrible situation you’re in. Who wouldn’t be?”
MEETING NICOLE
At that point, Nicole was referred to me. Because of our biweekly meetings to discuss patients at the clinic, I was already aware of her case.
She had been diagnosed with and treated for Lyme with only a partial response to therapy. What were we missing? After reviewing the reports of the other physicians and taking Nicole’s history myself, I ran blood tests for heavy metals.
The first test came back negative. I explained to Nicole that if she did have heavy metal toxicity and the test was negative, the metals were not actively circulating in her blood. Another test would tell us if they were being harbored in her bones and tissue.
The results of the second test showed that Nicole had a significant amount of lead in her tissues. Lead, mercury, arsenic, and other heavy metals are ubiquitous in our environment, and there are many potential sources of poisoning. Heavy metals poison many enzyme systems in the body and can cause a number of illnesses, but they especially damage our nerves and brain.
Nicole had suffered from lead poisoning as a child after eating paint chips, but she was unsure whether she had ever been treated. That episode and decades of exposure to the fumes from leaded gasoline left me suspicious that heavy metals, festering in her tissues, were interfering with her recovery.
Treating the whole patient often requires careful decisions about which issues to address first. Despite the standard recommendations of the CDC in general, recent studies have shown that more than 20 percent of people with Lyme develop what the CDC calls post-treatment Lyme disease syndrome (PTLDS).2 In those people, Lyme persists after treatment, evading the standard course of antibiotics.3 Because of this, the duration and type of antibiotic treatment must be tailored to each patient. Many physicians believe that treatment for Lyme must continue until the patient has been symptom free for at least a month.
One of the concerns is that when patients develop PTLDS, it is because some unseen factor is suppressing their immune system, inhibiting their recovery. In Nicole’s case, I wondered if the elevated lead levels in her body were creating that effect. Lead poisoning could have been responsible for some of her symptoms, and it might also have been keeping her from recovering from Lyme.
The treatment for Nicole’s lead poisoning could be handled quickly with chelation therapy, which might relieve her symptoms, as well as improve her immune function, but we could not do it while she was taking antibiotics. So I took her off the antibiotics, treated her for lead poisoning with oral chelation therapy, then put her back on antibiotics for Lyme.
As the months went by, Nicole’s memory gradually began to come back. The shaking became more moderate. The area of numbness on her right side began to diminish as well, proving it had never been multiple sclerosis.
“If this had gone much further,” Nicole said, “I think I would’ve been in a wheelchair for life.”
After she finished the second course of antibiotics, I put her on Atacand, a blood pressure medication, and low-dose naltrexone to quell the inflammation. My research indicated that the inflammation in the brain caused by Lyme and Lyme-related diseases could not be reduced by antibiotics and antiparasitic medications alone.
I prescribed low-dose Naltrexone, a very versatile medication. It is used in emergency rooms to save the lives of patients who have overdosed on drugs. By counteracting the addictive high of morphine, heroin, and alcohol, it has also given substance abusers relief from their addictions. My research has shown that Naltrexone acts to reduce inflammation in the brain. That makes it useful in treating conditions such as fibromyalgia and Lyme-related diseases, where antibiotics alone do not result in total recovery.
THE PRACTICE OF PARTIAL RECOVERY
If it was already obvious in medical school that people were suffering from increasingly complicated conditions, it was even worse now. The patients we saw at the clinic had often seen 8 to 15 other physicians before coming to the center. It was not uncommon for them to have been evaluated and treated at some of our best medical centers such as Mayo Clinic and Johns Hopkins. We were still able to help most of the people who came to see us, but achieving total recovery was proving more elusive.
The underlying mechanism was still a mystery. And I knew that until we found the cause, we would never find a cure.
With our patients exhibiting such a wide array of symptoms, it was nearly impossible to see the connection. How were physical injuries, viral infections, nutritional deficits, hormonal imbalances, and emotional disorders related? What was the common denominator?
Again and again, my mind kept returning to the common occurrence of pain and depression in the same people. Some of the people who experienced chronic pain may already have been prone to mood disorders, of course. For others, the persistent physical misery of chronic pain may have given way to a feeling of despair. But even taking those two possibilities into account, the number of people who had both pain and depression was inexplicably high.
In the general population, approximately 16 percent will experience a major bout of depression in their lives, while 15 percent will experience chronic pain in any given year. Of those people, 65 percent will experience both at the same time.4
There was also a growing recognition that people who had both conditions together had a dramatically lower chance of recovery with our current treatments. The odds of recovering from a major bout of depression were 47 percent. If a patient had both pain and depression, the likelihood of recovery dropped precipitously to 9 percent.5
It was obvious what was happening, but why was it happening?
DIGGING DEEPER
Dr. José Apud and I often had long conversations, wondering what it was that brought our specialties—pain management and psychiatry—together so frequently. As new research would come out, we would pour over it in the study group, looking for clues that could explain the connection between these two conditions.
Judging by the deterioration I was seeing in the patients who arrived at my clinic, I was starting to suspect that both pain and depression were neurodegenerative. But I was spending hours reading medical journals, and none of the literature was talking about it.
It was slowly dawning on me that if I was determined to isolate the underlying mechanisms of these conditions, I was going to have to go deeper into neurophysiology than I’d expected. In medical school, I’d originally planned to become a neurologist. Now it looked like I was going to end up going down that road after all. Compiling all the latest studies on neuroinflammation in depression, I dug in, assuming I was going to have to put myself through a mini-master’s program in neurophysiology before I found anything that could help the patients with complicated conditions.
Months went by. Each time I found something of interest, I would take it to the group or discuss it with Dr. Apud, but I didn’t find anything too enlightening at first.
Late one night, I came across a paper by neurologist Michael J. Robinson and his colleagues at Eli Lilly, one of the largest pharmaceutical companies in the world. Examining pain and depression from a neurological point of view, he found they had more in common than the medical community had assumed. In fact, they shared much of the same neurophysiology. More exciting, however, were his arguments that these were both neuroinflammatory diseases.6
This was a breakthrough insight. I rushed the data to the study group, and we set to work, trying to grasp the implications. Two questions were foremost in my mind:
• If pain and depression shared a similar neurological base, were they two separate diseases or different manifestations of the same disease?
• And when they occurred together, what made them ignite a synergy, creating a condition that was more than the sum of its parts?
The idea that pain and depression were inflammatory diseases was a radically new concept. It would require a completely different approach than either physicians or psychiatrists had been using to evaluate and treat patients.
In 2009, we understood very little about the nature of inflammation in the central nervous system. The brain is considered “an immunologically privileged” organ. Our brains have their own unique immune systems. While the brain’s immune system can and does interact with the peripheral immune system, that interaction is limited and closely regulated.
The brain and spinal cord, which make up the central nervous system (CNS), are connected to every organ and limb by the peripheral nervous system. Because of its vital importance, the CNS is completely encased in bone. From the top of our skulls to the base our spines, it is shielded from external assaults. Deep inside, our brains are protected from contamination by the blood-brain barrier. As R. Douglas Fields explains in The Other Brain, “The cells forming the walls of blood vessels in the central nervous system are sealed together so tightly that cells and molecules in the bloodstream, which freely pass into tissue elsewhere in the body, are unable to cross into brain tissue.”7 It was widely assumed that because of this barrier, brain inflammation was rare, the result of extreme illnesses or violent injuries.
Curiously enough, the response of patients with hepatitis was raising questions about these assumptions. When they were treated with interferon, these patients consistently became clinically depressed.8 Since interferon is one of the molecules that causes inflammation in the body, researchers came to suspect that there was an undiscovered link between inflammation and depression.
In the last few years, as they began to investigate, they discovered that anxiety disorders and PTSD also accompanied elevated inflammatory molecules in the central nervous system. This led to the astonishing conclusion that depression, anxiety, and PTSD were all neuroinflammatory diseases in the brain.9
It is important to clarify what we mean when we talk about inflammation. There are many different types of inflammatory pathways in the body. When we call all of them “inflammation,” it’s like talking generally about “illness.” Physiologically, each type of inflammation is very different, engaging different types of cells and different parts of the immune system.
At the simplest level, inflammation associated with allergies is mediated by one pathway (IgE), food intolerances by another (IgG), and celiac disease by others (IgA and IgG anti-tTG). Bacterial infections cause inflammation by a completely different route (the activation of white cells), while biotoxic inflammation involves cytokines and interferon.
We may use an antibiotic to treat the inflammation from a bacterial infection, but the same antibiotic would be completely ineffective in treating an allergic response, just as the antihistamines or steroids we might use to treat an allergy would do little to combat bacteria.
What we’re just beginning to understand is that inflammation quickly gets complicated. Depending on how many cumulative traumas the body has endured, inflammation can spread like a brush fire. When it flares up in one pathway, it can ignite a secondary inflammatory response in peripheral pathways.
Inflammation has been a hot topic in medicine for the last 10 years. Within the integrative medical community, many chronic diseases are being seen as a consequence of chronic inflammation throughout the body. New studies are confirming neurodegeneration that is the result of sustained low-grade inflammatory states. There is speculation that central nervous system inflammation may be a precursor to all kinds of conditions, from autism to fibromyalgia to Alzheimer’s.10 It is even thought that inflammation in the spinal cord may be a mechanism for chronic pain.11
In 2009, Dr. Robinson and his team were among the early researchers to connect both pain and depression to inflammation in the brain. If they were right that pain and depression were neuroinflammatory diseases with a common origin, the real question was: What was causing and sustaining that inflammation?
FINDING THE CONNECTION
While I was mulling it over, I attended a seminar at the American Academy of Pain Management about inflammatory factors in the brain—interleukins, a group of signaling molecules that participate in the body’s immune responses, and the tiny cells that would change my whole way of thinking: microglia.
The more I read about microglia, the more I was convinced that they played an important role in the development of pain and depression.
Microglia act as the resident immune system of the central nervous system. If anything manages to slip past the blood-brain barrier, the microglia intervene. “Squeezing between tangles of dendrites and axons as they rush to kill the invader, microglia attack and devour any harmful organism.”12
In order to protect the brain, the microglia secrete inflammatory chemicals to create swelling that acts as a buffer, as they work to destroy the invaders. While this inflammatory counterattack is going on at the molecular level, the person enduring it begins to feel sick with fatigue, headaches, fevers, and achiness all over.
As I began to investigate microglia, I found dozens of articles in medical journals, each one linking microglial inflammation to a different stressor: physical injury, psychological trauma, loss of oxygen to the brain, bacterial infections, viral infections, environmental toxins—the list was long. Whenever the central nervous system was stressed, the microglia upregulated, responding the only way they knew how: by creating inflammation.
And suddenly I saw it.
When microglia are upregulated, they create widespread inflammation in the central nervous system. If they are turned on too often, they become hyperreactive, keeping the brain in a chronic state of inflammation.
In some people, the microglia remain activated for longer periods of time. We see evidence of this in teenagers who binge drink. Heavy alcohol consumption triggers the microglia. Researchers in one study confirmed that teenagers’ nervous systems were measurably inflamed, then checked their levels of inflammation at intervals to see when it subsided. (Inflammatory chemicals, Interleukin-6, TNF alpha, and Interleukin-1 beta are clear biomarkers for upregulation of microglia because they are produced by microglia in the brain.) After the teenagers stopped drinking, their microglia remained upregulated for a decade.13
What this study demonstrates is two very important concepts. The first is that the traumas we suffer have a cumulative effect. Every injury, every infection, every toxin, every physical trauma, every emotional blow generates the same reaction. Inside the brain, it triggers the microglia again and again and again.
The second realization is even more startling. There comes a point when the microglia have been activated in such a way that they remain upregulated, continuing to spew out inflammatory chemicals even though the trauma that originally caused them to become active is no longer present. That response can show up in any number of ways: chronic pain, depression, anxiety disorders, fibromyalgia, chronic headaches, and PTSD, to name a few. All of these and many other medical conditions are the manifestation of chronic microglia activation.
No matter how it shows up, any condition that is caused by the activation of microglia is just a variation on the theme. Genetic proclivities or the particular combination of cumulative assaults result in different manifestations, but at the physiological level, one single underlying process is taking place.
Now I had a target, a way of understanding inflammation in the central nervous system. My first goal was to identify everything that makes the microglia start setting fires in the brain. Treating those things would surely improve my patients’ conditions.
The second goal would be to understand how to turn off the microglia and return them to their non-inflammatory resting state once their job of protecting the brain from the original trauma was completed.
But the implications were even greater than that. Medicine was getting it all wrong. Chronic pain in all its forms—depression, PTSD, and a number of other neuropsychiatric conditions—were not distinct diseases but symptoms of an underlying neuroinflammatory disease. The cause of that inflammation was chronically upregulated microglia.
