Insulin Resistance and Chronic Pain
An estimated 10 million adults in the United States live with fibromyalgia — a condition that causes pain throughout the body often to the point where it’s difficult to function. Could the key to understanding and treating fibromyalgia and other chronic pain involve insulin resistance? We will shed some light on current research on this topic.
Characterized by chronic and widespread pain, increased sensitivity to pain, and heightened feelings of fatigue, brain fog, etc., fibromyalgia remains poorly understood. The condition is also hard to diagnose, difficult to manage, and diminishes the quality of life for those struggling with it. It is reported that there’s an estimated global prevalence of 2.7%, with females outnumbering males nearly three to one. In addition, a couple of studies have noted that fibromyalgia seems to be more prevalent among individuals with Type 2 diabetes (T2d) suggesting a link between the two conditions that is worthy of further study. While experts agree that genetics and environmental factors are at play with fibromyalgia, little is known regarding how and why the syndrome develops.
Diagnostic criteria for fibromyalgia comes from the American College of Rheumatology (ACR) guidelines. The Widespread Pain Index measures pain or tenderness felt in the week prior to the appointment in 19 different body regions. The Severity Scale is deduced by the patient’s reporting the severity of symptoms like fatigue and brain fog on a scale from 0 to 3. ACR guidelines combine these two measurements using a rating scale from 0 to 31, and according to them, a score of 13 or higher corresponds to a diagnosis of fibromyalgia.
The global economic impact of FM is enormous. In the United States alone, the healthcare cost is around $100 billion/year and is comparable to reports in European countries. Due to lower pain thresholds, patients with FM also have a higher incidence of symptomatic musculoskeletal and spinal disorders which in themselves contribute to the financial burden of managing this disorder.
Many hypotheses have been advanced to explain the extensive array of symptoms including inherited abnormalities, dysfunction of neurotransmitter pathways such as substance P, immune dysregulation, and several others. Unfortunately, none of these propositions has led to practical advances beyond symptomatic treatment. In fact, recent reviews of FM published in 2016 and 2017 have concluded that there have been no substantive advances in our understanding of this disease.
Although more recent reviews of fibromyalgia research do not make mention of the purported link between the syndrome and insulin resistance or diabetes, the two conditions affect brain vasculature in strikingly similar ways.
According to Miguel Pappolla, MD, PhD, a professor of neurology at the University of Texas Medical Branch and medical director of St. Michael’s Pain and Spine Clinics in Houston, insulin resistance is known to impair brain microcirculation leading to slowed blood flow and oxygenation (hypo-perfusion) in certain brain regions. “What is very interesting,” he said, “is that patients with fibromyalgia also have hypo-perfusion in several brain areas.” The question remains, however, whether insulin resistance may be behind these similar decreases in blood flow experienced by those with fibromyalgia.
To investigate this question, Dr. Pappolla led a retrospective, cross-sectional study, reviewing medical records from 23 patients (21 females, 2 males; 11 White, 8 Hispanic, 4 African American; ages 35 to 60) at St. Michael’s Pain and Spine Clinics.7 All 23 patients met the ACR criteria for diagnosis with fibromyalgia.
As a measure of insulin resistance, the team selected the hemoglobin A1c, in which values between 5.7 and 6.4 define prediabetes and values of 6.5 or more constitute diabetes. They compared the A1cs on record for the 23 patients with fibromyalgia to those of two separate control groups: the non-diabetic subset (1,350 people) from the Framingham Offspring Study characterized by normal glucose tolerance (FOS NGT) and the non-diabetic subset (1,592 people) from the National Health and Nutrition Examination Survey (NHANES).
When the investigators compared the A1c test results of the people with fibromyalgia with those of age-matched controls, they found that the former group had significantly higher levels of hemoglobin A1c than the latter indicating a measure of insulin resistance.
“[People with prediabetes] with slightly elevated A1c values carry a higher risk of developing central (brain) pain, a hallmark of fibromyalgia and other chronic pain disorders,” notes Dr. Pappolla, pointing out that this link between insulin resistance and fibromyalgia has been around for a long time. Surprisingly, this link went unnoticed. “Considering the extensive research on fibromyalgia, we were puzzled that prior studies had overlooked this simple connection,” the first author says.
“The main reason for this oversight is that about half of fibromyalgia patients have A1c values currently considered within the normal range. However, this is the first study to analyze these levels normalized for the person’s age, as optimal A1c levels do vary throughout life,” the researcher continues.
“Adjustment for the patients’ age was critical in highlighting the differences between patients and control subjects,” he explains.
As part of the study, the researchers administered metformin — a drug that people typically take to treat insulin resistance — to the participants with fibromyalgia and muscular or connective tissue pain.
Metformin successfully reduced pain in this cohort, prompting the researchers to suggest that this common drug could be a viable and less expensive treatment option for some people with this chronic pain condition.
“In the [U.S.] alone, the healthcare cost is around $100 billion [per] year; comparable to reports in European countries,” the researchers write in the study paper.
“Earlier studies discovered that insulin resistance causes dysfunction within the brain’s small blood vessels. Since this issue is also present in fibromyalgia, we investigated whether insulin resistance is the missing link in this disorder.”
First author Dr. Miguel Pappolla
“We showed that most — if not all — patients with fibromyalgia can be identified by their A1c levels, which reflects average blood sugar levels over the past 2 to 3 months,” Dr. Pappolla adds.
The A1c test is a blood test that allows doctors to measure a person’s blood sugar levels by looking at “hemoglobin A1c,” a blood cell protein that binds to the simple sugar glucose. Doctors use this test to diagnose prediabetes and type 2 diabetes
In order to supplement this finding, the evolution of the pain scores of patients with FM who had had their Insulin Resistance treated pharmacologically was also reviewed. This subgroup of patients reported dramatic improvements of their myofascial pain after treatment with metformin.
This evidence, although preliminary, suggests a pathogenetic relationship between Fibromyalgia and Insulin Resistance, which may lead to better treatment plans. Along with this, Metformin, a drug commonly used to treat diabetes patients by targeting insulin resistance, has shown promise with treating pain from fibromyalgia; it may translate not only into a radical paradigm shift for the management of [fibromyalgia] but may also save billions of dollars to healthcare systems around the world.
That said more research is needed to better understand the link between insulin resistance and fibromyalgia and other types of chronic pain.