The persistent widespread body pain that characterizes fibromyalgia has peripheral (e.g., mitochondrial and inflammatory) and central (i.e., brain and spinal cord) origins. Central sensitization describes the phenomenon characterized by increased sensitivity in the brain and spinal cord to pain signals and signals interpreted as pain which would not otherwise be perceived as such. Peripheral abnormalities seen in fibromyalgia include mitochondrial dysfunction, intestinal hyperpermeability, systemic inflammation, DNA damage, oxidative stress; obviously these abnormalities do not originate from within the central nervous system but are generated from elsewhere
in the body.
The “drug deficiency model of fibromyalgia” postulates that the condition is idiopathic and therefore necessarily treated with pharmaceutical drugs. According to the American Pain Society in May 2015, fibromyalgia is a “chronic” pain disorder that originates from the brain and spinal cord and requires treatment with analgesic drugs.16 Despite the mountain of research substantiating the integrated model of the microbial and metabolic origins of fibromyalgia17, science writers funded by drug companies describe central sensitization as idiopathic and necessarily treated with painrelieving drugs; noteworthy is the fact that all of the FDA-approved drugs for fibromyalgia are expensive (range $100-200 per month per drug) and have adverse effects including weight gain, seizures, life-threatening allergic reactions, hepatic toxicity, depression, suicide, and other causes of injury and death.18
The “microbial and metabolic model of fibromyalgia” shows that small intestinal bacterial overgrowth (SIBO) which is common in clinical practice is notably more common—up to 100% in some studies—in patients with fibromyalgia and that the severity of SIBO correlates with the severity of fibromyalgia, thereby supporting a dosedependent causal relationship. Central sensitization can result from exposure to microbial molecules such as bacterial endotoxin and the resulting inflammatory response which triggers Toll-like receptor 4 (TLR4) in the brain’s microglial cells, causing astrocytes to promote excitatory glutaminergic neurotransmission19 which promotes pain perception, depression, central fatigue, and neurodegeneration. Consistent with this model is the finding that microbial metabolites from gastrointestinal bacteria such as hydrogen sulfide (H2S) and D-lactate can induce mitochondrial dysfunction, as can bacterial lipopolysaccharide (LPS, endotoxin). This model explains why fibromyalgia patients respond to treatments that support mitochondrial function (e.g., coenzyme Q10 300 mg/d20) as well as treatments that directly address the small intestine bacterial overgrowth (SIBO).21
Small intestine bacterial overgrowth leads to secondary central sensitization and mitochondrial dysfunction in fibromyalgia: 1) Bacterial endotoxin from small intestine bacterial overgrowth (SIBO) and increased intestinal permeability leads to the systemic release of inflammatory cytokines and prostaglandins, which readily cross the blood-brain barrier. LPS can activate TLR4 on microglial cells, which are also triggered by inflammatory mediators. 2) Microglial activation leads to 3) astrocyte activation and the 4) resultant increased glutaminergic neurotransmission, which promotes 5) central sensitization to pain, also depression and central fatigue. Bacterial endo-toxin and metabolites such as H2S and D-lactate impair mitochondrial performance, leading to the mitochondrial dysfunction that is well known to characterize fibromyalgia and which leads to muscle pain, fatigue, and exercise intol-erance.