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BRAIN INFLAMMATION BLOG #1: The New Paradigm* for the Treatment of Chronic Pain Disorders

Dr Alex Vasquez, 25 April 2016

Note: Dr Vasquez's expertise on the topics of fibromyalgia, dysbiosis, nutrition, functional medicine, clinical medicine, and microbiome/dysbiosis is demonstrated by the following publications (and more) plus numerous international post-graduate presentations since 2001: 

  1. Neuroinflammation in fibromyalgia and CRPS is multifactorial. Nature Reviews Rheumatology 2016 Mar PDF

  2. The Microbiome Arrives to Prime Time in Primary Care, Implications for the Anti-Dysbiotic Treatment of Fibromyalgia. Nutritional Perspectives 2015 Oct PDF

  3. Translating Microbiome (Microbiota) and Dysbiosis Research into Clinical Practice: The 20-Year Development of a Structured Approach that Gives Actionable Form to Intellectual Concepts. International Journal of Human Nutrition and Functional Medicine  2015 Jun PDF

  4. Inflammation Mastery, 4th Edition (and thereafter). 2016 PDF of samples

  5. Mitochondrial Medicine Arrives to Prime Time in Clinical Care: Nutritional Biochemistry and Mitochondrial Hyperpermeability (“Leaky Mitochondria”) Meet Disease Pathogenesis and Clinical Interventions. Integr Med 2014 Aug

History of previous work: Most people --especially clinicians and healthcare students-- who are familiar with my work know that most of my teaching originated from the work that I did when I started teaching Orthopedics and Rheumatology for the Naturopathic Medicine Program at Bastyr University in 2000 and 2001; from those seedling course notes blossomed the books initially published as Integrative Orthopedics (2004, 2007, 2011), Integrative Rheumatology (2006, 2007, 2014 and now published as Inflammation Mastery, 4th Edition in 2016) and also Musculoskeletal Pain: Expanded Clinical Strategies, commissioned by the Institute for Functional Medicine in 2008. During all these years, I have published more than 100 professional articles and letters on the topics of nutrition and pain and inflammation, and I have given innumerable post-graduate presentations internationally. Many of my articles such as on vitamin D (2004) and mitochondrial nutrition (2014) have been potent "paradigm shifts" in the way clinicians view specific problems and solutions in clinical practice. Likewise, my most recent major article is titled "Neuroinflammation in fibromyalgia and CRPS is multifactorial" published in Nature Reviews Rheumatology (March 2016).



The way we previously viewed pain and inflammation: Previously, we were aware of local inflammation (such as occurs following an acute injury or trauma), and then later we became aware of systemic inflammation in the absence of trauma (such as occurs with obesity, diabetes, and cardiovascular disease). From a medical standpoint, we have used anti-inflammatory drugs such as NSAIDs (non-steroidal antiinflammatory drugs, such as aspirin and naproxin) and DMARDs (disease-modifying antiinflammatory drugs, such as prednisone and methotrexate and later the "biologics" which target TNF). From a nutritional standpoint, we used and have continued to use natural and nutritional antiinflammatory interventions such as diet (review part 1, 2004), n3 fatty acids (review part 2, 2005), ginger and other nutrients (review part 3, 2005), targeted inhibition of NFkB (review part 4, 2005) and correction of dysbiosis (review part 6, 2006). With the development of my "functional inflammology protocol" (first presented and published in 2012; see video introduction from our 2013 International Conference on Human Nutrition and Functional Medicine) we have progressively appreciated that we can change immunocyte phenotype via nutritional interventions, what I have called "nutritional immunomodulation" most recently detailed in Chapter 5 of Inflammation Mastery, 4th Edition and identically in the two-volume set Textbook of Clinical Nutrition and Functional Medicine, Volume 2 (2016).



The way we must currently view pain and inflammation: What is becoming clear --both from the science as well as the pharmaceutical industry's attempt to exploit that science-- is that pain and inflammation are inextricably intertwined. Simplistically yet accurately, we can state that inflammation promotes (amplifies) pain, and also that pain promotes (neuro)inflammation. I diagrammed this relationship in the updated version (2016) of my work on migraine (originally published in 2004) and fibromyalgia (originally published in 2008); this is available in Chapter 5 of my 4th Edition work (op cit) and also in a separate monographPain Revolution (full color) and Brain Inflammation (grayscale). I underscored this concept in a recent press release; with more thought and reflection and reading, I have progressively understood this concept at a deeper level. As I have shown on the book covers of Pain Revolution and Brain Inflammation, these are vicious cycles. Pain triggers neuroinflammation which promotes neurogenic inflammation for additional pain and inflammation. Beyond that and within that, mitochondrial dysfunction is triggered by inflammation while also promoting neuronal hypersensitivity, promoting neuroexcitation and additional depolarization, additional pain reception, and additional inflammation. Thus, pain and inflammation are not simply associated; they are unified, united, identical. One creates the other so that they (can and often do) become one continuum. Thus, we may one day use a cojoined term such as painflammation to connect and express our understanding of the connection between pain and inflammation and how chronic pain is dependent on brainflammation while pain (sensory reception of nociceptive signals) also leads to inflammation of nerves, brain regions.


Video: For best viewing of this video due to its vertical orientation, click for full-screen view. 

BRAIN INFLAMMATION BLOG #2: The Hijacking of Fibromyalgia

Dr Alex Vasquez, 16 May 2016

I was right in 2008 and 2011: In 2008, I published the first (to my knowledge) integrated model of fibromyalgia in a CME monograph commissioned by the Institute for Functional Medicine. In 2011 I created the video immediately below based on the book I had just published titled Migraine Headaches, Hypothyroidism, and Fibromyalgia which has now been replaced by the full-color Pain Revolution in Migraine and Fibromyalgia(digital ebook available) and the cheaper grayscale excerpt Brain Inflammation in Chronic Pain (same digital ebook); that information is excerpted from the much larger Inflammation Mastery 4th Edition (complete work, Chapters 1-5) and Textbook of Clinical Nutrition and Functional Medicine (Chapter 5 only, because many people told me they wanted the work available in two volumes).

1) Drug company-sponsored authors have rewritten the diagnostic criteria to make the criteria broader (more drug sales) and more durable (more difficult to excape the diagnosis) to result in more patients being diagnosed with fibromyalgia = more patients = more drug sales: What I proposed then was that the re-writing of the diagnostic criteria was funded by the drug companies who wanted to make the diagnosis 1) available to more people, 2) for longer periods of time, and 3) without the need for a doctor's exam so that patients could diagnose themselves over the internet and then demand drugs. I am still quite sure that is what happened. 

2) Drug-company funding of review articles pushes more drugs on more patients: Selling drugs requires convincing doctors that drugs are the best treatment. That is exactly what has happened. Look at most review articles on fibromyalgia and you will find that either/both 1) the authors are funded directly (payment) or indirectly (medical school research grants), and/or 2) the citation of work published by such drug company employees. 

3) Drug companies continue to manipulate the science on fibromyalgia: See Brain Inflammation Blog #1 and be sure to see the video from 2016 recorded in Paris (introduction, provided above). 

BRAIN INFLAMMATION BLOG #3: Largest Disease-Specific Genome Test Fails to Find Actionable Associations in Migraine, Reinforcing the Perspective that Genomic Testing is Barking up the Wrong Tree

Dr Alex Vasquez, 29 Sep 2016

Dr V's perspective on new research recently summarized in the journal Genome Medicine:  I readily admit that while I appreciate the potential promise of so-called genomic "precision medicine", I am also of the opinion that the rabid over-enthusiasm for this technology is fueled by the profiteering motives of 1) data compilation and distribution, 2) maintaining current status quo of drug dependency by a) associating specific genes with specific drugs, and b) promoting inertia while the medical community sits on its hands awaiting the never-quite-ready delivery of the promise of genomic/precision medicine, which although valid in premise in rare instances is largely ridiculously reductionistic in its basis and attempt to prove that diseases are based on genetic defects in need of pharmacologic repair. Also, with my having reviewed the research and pathophysiology of migraine for the past 17 years and via the publication of many articles and book chapters, I am far from convinced that a somatic gene defect is going to be found that then translates into a medical miracle that alleviates this condition because 1) many non-genetic contributors have already been identified, and 2) the mitochondrial model of the disease as I have summarized in my recent books such as Brain Inflammation / Pain Revolution, excerpted from Inflammation Mastery 4th Edition is the most durable and complete model of the disease ever published, elegantly simple though it may be. My main thesis is that migraine is a disorder of mitochondrial function with secondary glial activation, neuron dysfunction, and tertiary pain; the failing of the largest GWA* ever conducted in the history of medicine to find any actionable associations reinforces the perspective that migraine is a phenotypic functional disorder and not a genotropic disorder, at least not as far as the nuclear genome is considered.


When a large study of a common disease finds virtually nothing, a reasonable conclusion is that the researchers are using a faulty paradigm of the disease: As "the most prevalent and disabling neurological disorder", migraine provides a large subject pool for research (and drug sales); this is a common disorder, the opposite of an orphan disease. Recently, the largest disease-specific *genome-wide association (GWA) study ever conducted in the history of medical science was completed, and it found nothing actionable that could be translated into clinical care. 

"The most recently published migraine study, comprising data from 375,000 individuals, represents the largest published GWA study of any specific disease. ... Although the advances in GWA studies represent major progress, it is perhaps too early to say whether, in the short term, the common variant loci found could directly help to influence patient care." Gormley et al. Migraine genetics: from genome-wide association studies to translational insights. Genome Medicine 2016; 8:86 DOI: 10.1186/s13073-016-0346-4

Migraine is a multicomponent functional disorder, not a genetic disease: The model of migraine that in my opinion provides the most complete and facile understanding of the condition is as follows: mitochondrial dysfunction causes metabolic fragility and increased ROS and inflammation, thereby promoting both glial activation and neocortical hyperexcitability; the vascular phenomena are secondary to the metabolic collapse involving the totality of the parenchyma as well as the ROS-induced and inflammation-induced changes in vasodilation/vasoconstriction, which create the vicious cycle of metabolic collapse that I have termed "pain revolution", depicted as a circle that interconnects mitochondrial fatigue, brain excitation, and glial inflammation. 

FOR CLARITY: Chapter 5.1b from Inflammation Mastery 4th Edition was published separately as

Pain Revolution in color and later as

Brain Inflammation in discounted grayscale; the digital versions are identical.

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BRAIN INFLAMMATION BLOG #4: Treating Pain and Inflammation Naturally—Part 9: The Microbiome Arrives to Prime Time in Primary Care, Implications for the Anti-Dysbiotic Treatment of Fibromyalgia  PDF of article with additional information and citations

Dr Alex Vasquez, 15 Nov 2016

Article abstract: Building upon previous reviews in this Journal, this new review discusses advances in our understanding of natural/nonpharmacologic treatments for disorders of pain and inflammation by extending the information detailed in Part 6, discussing the role of the microbiome and dysbiosis in musculoskeletal disorders of persistent pain and inflammation. Following the introduction, a survey of the history of and recent developments in the study of the microbiome and dysbiosis will be provided; thereafter, fibromyalgia will be used as an example of dysbiosis-induced disease, exemplifying dysbiotic mitochondriopathy along with microbe-induced microglial activation as the cause of central sensitization and pain amplification.

Overview (Part 1) of the Functional Inflammology Protocol

Dr Vasquez introduces the "Functional Inflammology Protocol" at the 2013 International Conference on Human Nutrition and Functional Medicine (PDF brochure)

Dr Vasquez's "functional inflammology protocol", famously recalled by the FINDSEX ® acronym, is reviewed in this presentation for its application to the three general types of inflammatory diseases/responses: 1) metabolic inflammation, including glial activation and emphasizing the component of mitochondrial dysfunction, 2) allergic inflammation, including asthma and eczema, and 3) autoimmune inflammation, including rheumatoid arthritis, psoriasis, and the many other conditions that Dr Vasquez has detailed in his books starting in 2004 (Integrative Orthopedics) and 2006 (Integrative Rheumatology, now published as Inflammation Mastery, 4th Edition)

Inflammation Mastery 4th Edition


Samples and excerpts:

Click on PDF (larger PDF with photos) to see inside; download ebook sample at Amazon


Overview (Part 2) of the Functional Inflammology Protocol

Dr Vasquez introduces the "Functional Inflammology Protocol" at the 2013 International Conference on Human Nutrition and Functional Medicine (PDF brochure)

Samples and excerpts:

Click on PDF (larger PDF with photos) to see inside; download ebook sample at Amazon


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