Fibromyalgia has long been a conundrum, with pain and widespread functional impairment, but no known biological basis. The absence of a biological explanation for fibromyalgia has led many to suggest a mental source for the pain and disability that affects 10 million people in the U.S.
A new discovery, published in the journal Pain Medicine, may solve the mystery as researchers believe the findings clearly demonstrate that fibromyalgia has a rational biological basis located in the skin.
Fibromyalgia is a severely debilitating affliction characterized by widespread deep tissue pain, tenderness in the hands and feet, fatigue, sleep disorders, and cognitive decline.
However, routine testing has been largely unable to detect a biological basis for fibromyalgia, and standard diagnosis is based upon subjective patient pain ratings, further raising questions about the true nature of the disease.
For many years, the disorder was believed to be psychosomatic (“in the head”) and often attributed to patients’ imagination or even faking illness.
Currently approved therapeutics that provide at least partial relief to some fibromyalgia patients are thought to act solely within the brain where imaging techniques have detected hyperactivity of unknown origin referred to as “central sensitization.”
The breakthrough was made by scientists at Integrated Tissue Dynamics LLC (Intidyn), as part of a fibromyalgia study based at Albany Medical College. Researchers discovered a unique peripheral neurovascular pathology consistently present in the skin of female fibromyalgia patients.
They believe this pathology may be a driving source of the reported symptoms.
“Instead of being in the brain, the pathology consists of excessive sensory nerve fibers around specialized blood vessel structures located in the palms of the hands,” said Dr. Frank Rice, president of Intidyn and the senior researcher on the study.
“This discovery provides concrete evidence of a fibromyalgia-specific pathology which can now be used for diagnosing the disease, and as a novel starting point for developing more effective therapeutics.”
Three years ago, Intidyn scientists published the discovery of an unknown nervous system function among the blood vessels in the skin in the journal PAIN.
As Rice explained, “we analyzed the skin of a particularly interesting patient who lacked all the numerous varieties of sensory nerve endings in the skin that supposedly accounted for our highly sensitive and richly nuanced sense of touch. Interestingly, however, this patient had surprisingly normal function in day to day tasks. But, the only sensory endings we detected in his skin were those around the blood vessels.
“We previously thought that these nerve endings were only involved in regulating blood flow at a subconscious level, yet here we had evidence that the blood vessel endings could also contribute to our conscious sense of touch… and also pain.”
Now, pharmaceutical companies Forest Laboratories and Eli Lilly have developed FDA-approved medications with similar functions (serotonin/norepinephrine reuptake inhibitors, SNRI) that provide at least some degree of relief for many fibromyalgia patients.
“Knowing how these drugs were supposed to work on molecules in the brain,” Dr. Phillip J. Albrecht added, “we had evidence that similar molecules were involved in the function of nerve endings on the blood vessels. Therefore, we hypothesized that fibromyalgia might involve a pathology in that location.”
As the results demonstrate, they were correct.
To analyze the nerve endings, researchers used a unique microscopic technology to study small skin biopsies (less than half the size of a pencil eraser) collected from the palms of fibromyalgia patients.
The study was limited to women, who have over twice the occurrence of fibromyalgia than men.
The team uncovered an enormous increase in sensory nerve fibers at specific sites within the blood vessels of the skin. These critical sites are tiny muscular valves, called arteriole-venule (AV) shunts, which form a direct connection between arterioles and venules.
According to Albrecht, “the excess sensory innervation may itself explain why fibromyalgia patients typically have especially tender and painful hands.
“But, in addition, since the sensory fibers are responsible for opening the shunts, they would become particularly active under cold conditions, which are generally very bothersome to fibromyalgia patients.“
“In addition to involvement in temperature regulation, an enormous proportion of our blood flow normally goes to our hands and feet. Far more than is needed for their metabolism,” Rice said.
“As such, the hands and the feet act as a reservoir from which blood flow can be diverted to other tissues of the body, such as muscles when we begin to exercise.
“Therefore, the pathology discovered among these shunts in the hands could be interfering with blood flow to the muscles throughout the body. This mismanaged blood flow could be the source of muscular pain and achiness, and the sense of fatigue which are thought to be due to a build-up of lactic acid and low levels of inflammation in fibromyalgia patients. This, in turn, could contribute to the hyperactvity in the brain.”
Albrecht also pointed out that alterations of normal blood flow may underlie other fibromyalgia symptoms, such as non-restful sleep or cognitive dysfunctions.
“The data do appear to fit with other published evidence demonstrating blood flow alterations to higher brain centers and the cerebral cortex of fibromyalgia patients,” he said.
Senior Research Chair of the Alan Edwards Center for Pain Research at McGill University, Dr. Gary Bennett, commented after seeing the results that “It is exciting that something has finally been found. We can hope that this new finding will lead to new treatments for fibromyalgia patients who now receive little or no relief from any medicine.”
This discovery of a distinct tissue pathology demonstrates that fibromyalgia is not “all in your head,” which should provide an enormous relief to fibromyalgia patients, change the clinical opinion of the disease and guide future approaches for successful treatments.
Source: Integrated Tissue Dynamics