Researchers discover a rational source of pain in skin of patients with fibromyalgia

Fibromyalgia, a painful condition affecting approximately 10 million people in the U.S., is not imaginary after all, as some doctors have believed. A discovery, published in June 2013 in PAIN MEDICINE (the journal of the American Academy of Pain Medicine), clearly now demonstrates that fibromyalgia may have 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." However, an underlying cause has not been determined, leaving many physicians still in doubt about the true origins or even the existence of the disorder.

Now, a breakthrough discovery by scientists at Integrated Tissue Dynamics LLC (Intidyn), as part of a fibromyalgia study based at Albany Medical College, has provided a biological rationale for this enigmatic disease. The small biotechnology research company, founded by neuroscientists Dr. Frank L. Rice and Dr. Phillip J. Albrecht, reports on a unique peripheral neurovascular pathology consistently present in the skin of female fibromyalgia patients which 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. 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."

Nerve Endings Come In Many Forms

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 Dr. 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". Dr. Rice continued, "We previously thought that these nerve endings were only involved in regulating blood flow at a subconscious level, yet here we had evidencs that the blood vessel endings could also contribute to our conscious sense of touch- and also pain."

Now, in collaboration with renowned Albany Medical Center neurologist and pain specialist Dr. Charles E. Argoff, the study primary investigator, and his collaborators Dr. James Wymer also at Albany Medical College and Dr. James Storey of Upstate Clinical Research Associates in Albany, NY, clinical research proposals were funded by Forest Laboratories and Eli Lilly. Both pharmaceutical companies 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. 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, Drs. Rice, Albrecht, and postdoctoral researcher Dr. Quanzhi Hou, used their unique microscopic technology to study small skin biopsies (less than half the size of a pencil eraser) collected from the palms of fibromyalgia patients, who were being diagnosed and treated by Drs. Argoff, Wymer, and Storey. The study was limited to women, who have over twice the occurrence of fibromyalgia than men. What the team uncovered was 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 (see diagram).

As Dr. Rice describes their function, "We are all taught that oxygenated blood flows from arterioles to capillaries, which then convey the deoxygenated blood to the venules. The AV shunts in the hand are unique in that they create a bypass of the capillary bed for the major purpose of regulating body temperature."

A Thermostat for the Skin

In humans, these types of shunts are unique to the palms of our hands and soles of our feet which work like the radiator in a car. Under warm conditions, the shunts close down to force blood into the capillaries at the surface of the skin in order to radiate heat from the body, and our hands get sweaty. Under cold conditions, the shunts open wide allowing blood to bypass the capillaries in order to conserve heat, and our hands get cold and put on gloves.

According to Dr. 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."

A role in regulating blood flow throughout the body.

Although they are mostly limited to the hands and feet, the shunts likely have another important function which could account for the widespread deep pain, achiness, and fatigue that occurs in 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" noted Dr. Rice. "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 fibromyalgia patients. This, in turn, could contribute to the hyperactvity in the brain."

Dr. Albrecht also points 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 stated. 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, while changing the clinical opinion of the disease and guiding future approaches for successful treatments.


  1. Stephen Rodrigues Stephen Rodrigues United States says:

    We are getting closer to the core reasons but the key issue still evades us. What we lack is the “key” cause.

    We know that patients are miserable with an array of signs and symptoms.  
    We know that our technology at this points can not easily see the ”key.” It is too small.
    We know it can’t be repaired with surgery.
    We know there is no pill or pill combo that will reverse all the symptoms.
    We know that it looks like medical problems that are due to deficiencies ie Thyroid.
    We know it looks like medical problems that are toxicity or poisoning or overdose ie Cholesterol meds or cancer meds.

    In the 50’s some doctors dabbled with a theory and therapy of stressed muscles and ligaments breakdown and repair called trigger points. These doctors use injection therapy with saline or glycerine and other chemicals. Trigger Point Injection or Prolotherapy are the names.
    In the 80’s it was thought that it was all in the head or mental.
    In the 90’s it was thought to be infectious either bacterial or viral.
    After the 90’s until the present we’ve discovered that we can not treat it with a magic pill or combo of pills.

    In the 90s, I had a minor ah-ha moment when a patient I was following was sincerely better despite all my pills and referrals with Acupuncture. Why? Possibly related to the trigger point theory.
    In the 90s early 2000, a Dr Gunn uses what he calls Intramuscular Stimulation to treat neuropathic pain problems. Possibly related to the trigger point theory.
    In the past decade a lot of my patients are getting great relief with massage and something called Myofascial Release Therapy. Possibly related to the trigger point theory.

    In 2013, what do we know is that we can begin the healing or repair process with a “Therapy Program.” Please don’t discriminate, all of these items have to be put into the pot to simmer and keep the healing process going. Pain patients have to be proactive in their care. Here are some therapies that can be done at home. Hourly, daily, weekly and monthly.

    Self-Care and hands-on care;
    >Regular physical therapy, massage therapy, sports medicine.
    >Chiropractic medicine.
    >Stretching, yoga and Pilates.
    >Aerobic and any exercise are vital.
    >Vitamins and minerals (Magnesium glycinate)
    >Sleep hygiene.
    >Stress management, Wellness, Mindfulness and forgiveness.
    >Get some Epsoms salts for tub soaking.
    >Get a high quality oral magnesium.
    >Get on the floor or bed and start stretching.
    >Get a foam roller to work on your upper and lower body area.
    >Swimming, Aqua-Therapy and Hot-tub Spa therapy.
    >Rolfing or other hands-on therapy.
    >Review this Youtube self-massage.
    >Use self-trigger point release with your hands or a Thera-cane.
    >Find a PT specialist who can perform “Spray and Stretch.”
    >Professional massage.
    >Find a John F. Barnes myofascial therapist.

    More invasive or minimally invasive care with Myofascial Release Therapy with needles.
    >Acupuncture of the body. (Not just the Ear, Foot or Scalp)
    >Formal Dry Needling
    >Prolotherapy (not alone)
    >Botox injections (rare)
    >Travell, MD Trigger Points Injections.

    I’ve been in medicine for a 30 years and this is unfortunately not a “ah-ha” moment. But a confirmation that FM has no key but is a pot of stuff that simmers down to the disease we see today. There is something at the core which is altering this microscopic change from healthy tissues to unhealthy tissue changes. Now we can see these changes at the microscopic level.

  2. Teresa Encinas Teresa Encinas United States says:

    I just wanna say Thank You for all your hard work! I have had FMS since 1999 and I've tried everything and nothing really works expect pain meds and that only takes the edge off. I hate taking pain meds but it is the only thing that helps me get thru the pain. They say we are addicted to pain meds.  I don't use them unless I absolutely have to.  I know that aquatic therapy helps but sometimes your just in so much pain you can't go to these places or anywhere else for that matter.  I pray that through research FMS will be at least manageable.  Thank You sincerely for all whom work on finding a cure for those of us with Fibromyalgia and for believing we are not crazy!

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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