We know that increased activation of the sympathetic nervous (fight or flight) system is present in fibromyalgia but is it contributing to the pain there? Martinez-Lavin (“When Stress Causes Distress”) has been hypothesizing that it’s been a key pain driver in FM for years.

He’s shown that levels of norepinephrine – the neurotransmitter that turns the SNS on – are positively correlated with pain in FM. The higher the NE levels – the higher the pain level. He’s also shown that FM patients in severe pain tend to have alterations in some genes that control sympathetic nervous system functioning.  The authors of this paper suggest that these findings suggest fibromyalgia may be similar to several to types of chronic regional pain syndrome (CRPS).

Autonomic nervous system

The autonomic nervous system affects every organ in the body

Other studies have associated increased SNS activity with poor sleep and reduced cognitive functioning in chronic fatigue syndrome (ME/CFS).  Increased SNS activity has  also been associated with increased fatigue in cancer survivors.

That may not mean that NE levels need to be particularly to cause pain. They may simply need to be high enough to send overly sensitive pain receptors into panic mode.  Both Younger and Miller believe a similar scenario may be playing out with the immune system and the brain in chronic fatigue syndrome. They hypothesize that the brain has become so sensitive to cytokines that even normal levels may be causing it to overreact.

No one, however, has directly attempted to correlate SNS functioning with pain in FM – until now.  These researchers assessed pain levels and examined a wide variety of autonomic nervous system measures in people with FM.

They also wanted to attempt to track down where the breakdowns are.  Do they occur in the brain or in the system that controls sympathetic nervous system activity in the muscles (baroreflex) – or both?

The Study 

Clin Exp Rheumatol. 2015 Mar-Apr;33(1 Suppl 88):53-7. Epub 2015 Mar 18. Relationship between sympathetic activity and pain intensity in fibromyalgia. Zamunér AR1, Barbic F2, Dipaola F2, Bulgheroni M2, Diana A3, Atzeni F4, Marchi A5, Sarzi-Puttini P6, Porta A7, Furlan R8.

The Brain

Heart Rate Variability (HRV) – The heart rate is regulated by a variety of electrical frequencies which provide a window into autonomic nervous system functioning. Low frequency (LF) electrical signals are regulated by the sympathetic nervous system branch of the autonomic nervous system. High frequency (HF) signals are regulated by the parasympathetic nervous system.

The Body

They also looked at sympathetic nervous system functioning in the body by examining baroreceptor activation and muscle sympathetic nerve activity (MSNA).

Baroreflex – Baroreflex receptors are stretch receptors found in the large blood vessels in the heart. As increasing blood pressure causes the walls of the blood vessels to stretch baroceptors send signals to the nucleus of the solitary tract (NTS) in the brainstem. The NTS then sends a message to the smooth muscles lining the blood vessels telling them to relax, thus lowering blood pressure.

Muscle Sympathetic Nerve Activity (MSNA) – MSNA refers to the activity of the small muscles in the walls of the blood vessels that control how large or narrow our blood vessels are.  When your blood pressure drops these muscles tighten up the blood vessels in order to keep driving blood to the tissues.  Increased MSNA activity (tightened blood vessels) also plays an important role in our ability to stand without blood pooling in our legs. These small muscles are entirely controlled by the baroreflex response.



An increased heart rate had no effect on pain levels but an imbalance between sympathetic and parasympathetic modulation of the heart rate did.  This study found that an increased LF/HF ratio (high sympathetic nervous system activity) was associated with increased pain in FM.

This part of the study is pointing not at the heart but the brain. It’s the brain, in particular, the hypothalamus and related  “autonomic control” areas that regulate electrical activity in the heart. The altered LF/HF ratio suggests that problems with “central” or brain driven autonomic nervous system regulation are present.


blood vessels

Smooth muscles in the blood vessels are regulated by the baro receptors

In this study, reduced baroreceptor activity was associated with increased pain in FM.  Increased MSNA activity – a reflection of the reduced baroreceptor activity – was also associated with increased pain.

The authors suggested that problems with baroreceptor firing may be impairing the NTS’s ability to inhibit sympathetic nervous system activity in the blood vessels. Other studies have suggested that increased baroreflex activation triggers anti-pain signals, something that’s not happening in fibromyalgia.

The study indicated both the brain and the baroceptors were not regulating the SNS properly and that sympathetic nervous system activity was enhanced both in the heart and the blood vessels.

Treatment Suggestion

The authors suggested Clonidine, a sympathetic nervous system suppressing drug. Clonidine also reduces blood pressure, the heart rate, glutamate release and substance P levels and has antihistamine effects. These are all potentially good things for ME/CFS or FM.


Clonidine made things worse in one ME/CFS study…Could it work in fibromyalgia?

Clonidine is used to treat a wide variety of disorders including high blood pressure, neuropathic pain, ADHD, night sweats, anxiety, alcohol and opioid withdrawal, restless leg syndrome, migraine and sleep disorders.

Clonidine seems like a good fit for either FM or ME/CFS and Dr. Peter Rowe has found it helpful with some of his young ME/CFS patients.

Wyller’s big 2013 ME/CFS study, however, found that low dose Clonidine not only did not help, but actually increased fatigue and decreased activity levels in his pediatric ‘chronic fatigue’ patients. Wyller’s vague definition of chronic fatigue puts a question mark on many of his results, but this study’s failure raises also questions about Clonidine’s effectiveness in ME/CFS.  Clonidine certainly is helpful for some – a smaller study had positive results – but perhaps not many.


Some intriguing work in rheumatoid arthritis (RA) might help explain why. The type of autonomic nervous system dysregulation found in ME/CFS and FM – increased sympathetic nervous system and decreased parasympathetic nervous system activity  – also occurs in RA.

First some background.  Pro-inflammatory cytokines in the body are able, via the vagus nerve, to upregulate sympathetic nervous system activity in the brain. The brain then turns up SNS activity in the body. A major immune regulator, the SNS then upregulates Th2 immune (antibody formation, inflammation) functioning and inhibits Th1 immune (intracellular pathogen) functioning – an immune pattern believed present in ME/CFS.

At some point an immune shift occurred

At some point an immune shift occurred

The ability of the SNS to enhance inflammation in this manner may explain why stress can cause flares in RA and other immune mediated diseases.

Nothing, however, is ever simple in the immune system. Animal models of RA show that an intriguing time and disease dependent pattern of SNS/immune activation is also present.

Prior to the onset of arthritis SNS activation increases inflammation but after arthritis onset SNS activation actually appears to decrease inflammation.  Some sort of immune network shift (aka Broderick) has clearly occurred.

This seemingly paradoxical shift  suggests the decreased SNS activation Wyller achieved in his study might have inadvertently increased his patients inflammation and fatigue. (For myself energy and tension reducing treatments work for a bit, but ultimately leave me feeling fluish, It’s as if the tension is there for a reason.).

This doesn’t mean that SNS activation is “good” but that it may not be all bad. It certainly means that our systems are very complex. SNS de-activation may help in some and not help in others.

New Treatment Approach Proposed

Multiple inflammation producers appear to be present in both RA and ME/CFS.  Increased SNS activity, low levels of the immune regulator cortisol, and reduced vagus nerve activity all may serve to increase inflammation in these disorders.


Enhancing the anti-inflammatory response might be helpful

The authors propose upregulating the activity of the other side of the ANS – the parasympathetic nervous system  – to bring down inflammation. The cholinergic anti-inflammatory pathway associated with the vagus nerve is a fairly recent discovery. A drug called GTS-21 that’s been tested in healthy controls, schizophrenia and Alzheimer’s is a possibility. Electrical vagus nerve stimulation is another. It’s being used in several diseases and was effective in re-balancing the immune system in refractory epilepsy.

Other Possibilities

pain and fatigue fibromyalgia

The autonomic nervous system may be producing both pain and immune problems in fibromyalgia

Studies indicate that mind/body practices such as yoga (introductory postures), Tai Chi, Qi-Gong, mindfulness and meditation techniques can help to rebalance the autonomic nervous system.  Several studies suggest QiGong and similar practices may be able to reduce pain to some extent in FM. The techniques Dan Moricoli used (pacing, light exercise, yoga, meditation) in his recovery all tend to suppress SNS activity and increase PNS activity.

A Naturopath proposes not over-doing exercise and the following to rebalance the ANS.

  • Supplementation  – The minerals calcium, magnesium, selenium, manganese and zinc are known for their calming effects, as are the amino acids GABA, and L-taurine and the herbs valerian, passionflower, skullcap and hops.
  • Destress – Try to reduce the stress in your life as much as possible. This can include physical stresses such as noise pollution, environmental toxins, electromagnetic pollution and spinal misalignment. 
  • Think positive –Try to promote your parasympathetic nervous system through the use of meditation, affirmations, and through watching, listening to, and reading uplifting books and other media.
  • Release negativity – Aim to steer clear of negative emotions such as fear, anxiety and blame.
  • Cultivate inner peace – Let go of the need to control and choose contentment and peace.
  • Breathe deeply – This activates the parasympathetic response and turns the sympathetic nervous system off. 
  • Meditate  – Make time to still your system and just be – even if for only a few minutes a couple of times a day.


Autonomic nervous dysregulation is contributing to the pain found in fibromyalgia and may be affecting immune activity as well. Various ways to rebalance the autonomic nervous system – from drugs, supplements, electrical vagus nerve stimulation and mind/body practices  – have been proposed.




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