From Top Down to Bottoms Up In Fibromyalgia

For the past decade or so research evidence has suggested that fibromyalgia is more a brain disorder than a body disorder. Studies indicating increased substance P levels, increased activity in the pain sensing and decreased activity of the pain inhibitory sections of the central nervous system suggest people with FM have a  nervous system primed to produce pain.   The central sensitization theory suggests FM is a ‘top-down’ disorder that starts in messed up circuits in the brain and goes down from there.

brain mri

Is the brain really the problem in fibromyalgia?

Recent studies taking a close look at the muscles and skin, particularly the stunning small fiber neuropathy findings, suggest it’s far too early to dismiss the body in FM.  In fact, some researchers are suggesting that the ‘central sensitization’ present may be driven by problems in the body – a stunning turnaround from a decade or so when the body was more less, excluded from the conversation.

This may not be just about fibromyalgia. If  this theory is right the pain and fatigue in ME/CFS and FM my very well come down to two common denominators in both diseases; the sympathetic nervous system and the blood.

Some Background

Let’s back up and look at some recent things we’ve learned regarding the SNS/blood interaction.

  •  Allodynia may be caused by an inflammatory cascade (ischemia) produced by low blood flows to the tissues.
  • Low blood flows to the muscles are present in both fibromyalgia and chronic fatigue syndrome.
  • ME/CFS patients appear to have such reduced aerobic functioning that they begin producing energy anaerobically very early in an exercise period.  Anaerobic energy production produces toxic metabolites that cause pain and inflammation.

Now a theory posits that anaerobic metabolites and inflammatory cytokines caused by low blood flows are driving the central nervous system sensitization present in fibromyalgia.  This theory suggests that small blood vessel constriction caused by an overactive sympathetic nervous system is the problem.

In this study, researchers looked for evidence of sympathetic nervous system/blood vessel problems in one of the most blood and blood vessel-rich areas of the body – the hands.

  • Pain Med. 2013 May 20. doi: 10.1111/pme.12139. Excessive Peptidergic Sensory Innervation of Cutaneous Arteriole-Venule Shunts (AVS) in the Palmar Glabrous Skin of Fibromyalgia Patients: Implications for Widespread Deep Tissue Pain and Fatigue. Albrecht PJHou QArgoff CEStorey JRWymer JPRice FL.

Small Caliber  Nerves – Big Caliber Effects?

Our hands are more than just tools.  It turns out that sensory and autonomic nervous system nerve fibers permeate the small blood vessels in our skin.  When we get too hot these small  ‘caliber’ blood vessels dilate, bringing blood to our surface to cool us. When we get too cold they help us retain heat by constricting and sending blood to our interior organs.

These researchers biopsied small pieces of skin in the hands of people with fibromyalgia to see what was going on in this area of intense nervous system and cardiovascular activity. If the sympathetic nervous system was messed up it should definitely show up there… and it did.


Taken together, these data indicate that FM patients have a neurovascular pathology in the palms of the hands predominantly increasing the peptidergic sensory innervation of the AVS.

nerves and blood vessles

The FM patient biopsy on the right show much greater nerve abundance around the blood vessels

Sensory nerves that relayed pain and other sensory signals and dilated the blood vessels abundance were highly abundant in the small shunts between the arteries and veins in the hands of the FM patients.

Loaded with small capillaries,  the hands of humans are not only important thermoregulatory’ devices but they’re also important reservoirs of blood.

It turns out that the blood flows to our hands far exceeds their metabolic demands. Our hands are essentially used as blood storage sites the body can access to quickly shunt blood to areas in need. Studies indicate that as soon as you start to exercise, for instance, blood flows out of your hands and into your muscles.

The high levels of sensory nerves found in the FM group suggested why some FM patients experience pain in their hands, particularly when it’s cold.

“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.“ The authors

Blood In…..Not Blood Out

The researchers found that the shunts between the arterioles and veins in the hands were highly innervated with blood vessel-dilating nerves suggesting that blood was able to easily find its way into the hands but not out of them.

Given the role the hands play as storage reservoirs for blood not being able to move that blood around could be a problem if you want to exercise, think hard or sleep. The authors suggested that fatigue during exercise, cognitive problems during thinking, and problems sleeping could all be a function of these dilated small blood vessels in FM patients’ hands.

Dilated blood vessels in the hands could mean less blood elsewhere in the body

Dilated blood vessels in the hands could mean less blood elsewhere in the body

With the blood stuck in the hands, the SNS  could be tightening blood vessels down elsewhere in an effort to squeeze what it has available out to the muscles and the brain.

Interestingly, given the gender imbalance in this disease, estrogen is a huge player in sensory nerve production in the hands and females typically, have twice the sensory innervation in their hands than men.

It seems a bit much to say FM is all in the hands but throw in problems with blood volume, dilated arteries elsewhere and issues with the mitochondrial uptake of oxygen, etc. with shunts that appear to be chronically open in one of the most blood-rich areas of the body, and maybe you really have something.

Perhaps the blood really will out in ME/CFS and fibromyalgia.

The authors are examining male FM patients to see if the same pattern applies.

New Treatments Possibly on Tap

They noted that SNRI drugs that act on the brain also act on the nerve endings in the skin and may be helpful in FM and assert the finding opens the door for new therapeutics.

“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.”

Senior Research Chair of the Alan Edwards Center for Pain Research at McGill University, Dr. Gary Bennett felt so, as well, stating

“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.”

  • Check out an excellent reader-friendly explanation of all this by the authors of the study.
  • Coming up soon: bottoms up indeed for FM;  the stunning small nerve fiber neuropathy findings suggest fibromyalgia should perhaps be called fibroneuralgia….

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