I was curious what sort of research there was on Fibromyalgia and our automatic nervous system (ANS) triggering the Fight, Flight or Freeze response.

My curiosity comes from the fact that some symptoms of my fibromyalgia seem to be symptoms of a triggered Fight, Flight or Freeze response. It is, after all, triggered from perceived threat and pain could be seen as a perceived threat by the body. Certainly, pain has certain psychological symptoms.

The specific symptoms I notice are ones like my heart rate changes. To a fast beat. And pounding. Also with pain, my breathing naturally changes. It becomes more shallow and quick. And with a fibromyalgia flare, I notice these a lot and do try to ‘calm my system’ down. I wondered what sort of link there may be with Fibromyalgia and our Fight/Flight/Freeze response.

Text: Fibromyalgia and the fight-flight-freeze response
Image: stressed sheep cartoon. Cartoon thought bubble with just tangled lines of stress thinking. Background color is dark blue with blotches of orange

When it comes to chronic pain in general and the stress response

Basically, when it comes to chronic pain and the Fight/Flight/Freeze response we are looking at a stress response on the body. Because chronic pain changes the nervous system to be ‘constantly ON’. And we all have particular ways chronic stress will activate our Fight/Flight/Freeze responses. One thing to note is that this creates a chronic stress situation in our bodies.

So with chronic pain, the brain is activating a stress response when there is no longer the ‘danger’ as in the threat of acute injury. So we are getting a stress response because of our pain, over and over and over again.

This will cause long-term effects of stress on the body. Long-term effects of the Fight/Flight being stuck ON

  • Increased heart rate
  • high blood pressure
  • Dizziness, sweats
  • Muscle contraction, shakes, headaches
  • Migraine
  • Nausea, stomach pain, ulcers
  • Brain fog
  • Memory problems
  • Being indecisive
  • Increased self-critical thoughts, negative thinking patterns (depressive thoughts), anxious thought patterns (excessive worrying)
  • self-isolation
  • Insomnia
  • Irritation

See more information from Source article: Chronic Pain and Stress

I think most of us are familiar with some of these and it does depend on how our bodies respond to the stress experience. For me, my heart rate increases and pounds like crazy… even though I perceive nothing to be the cause for this. I have a lot of muscle tension and a tremor that comes and goes. I have chronic migraine with aura and when I do not have a migraine I have a headache. With fibromyalgia of course I am familiar with brain fog, insomnia and memory issues. I am pretty skilled at self-critical thoughts and negative thinking but I am way better than I used to be with unmanaged depression (I was a real dick to myself back then. Never gave myself a break. Ever).

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Specific research on Fibromyalgia

Fibromyalgia is chronic pain, so the above does apply to it as far as I can tell. We do deal with a chronic stress situation for sure.

Neuroinflamation and Fight/Flight response with Fibromyalgia

Sustained Stimulation of β2- and β3-adrenergic Receptors Leads to Persistent Functional Pain and Neuroinflammation. 

There is some research to suggest the neuroinflammation seen with fibromyalgia could be linked to a stress response from within the hypothalamus.

2018 Chinese-Duke University collaboration suggested that the stress response and neuroinflammation are linked as well, although in a different way. The appearance of these hypotheses and findings is good news given that neuroinflammation appears (but has not been definitively proven) to be present in these diseases, and evidence suggests that the stress response is certainly off.


Apparently, the research suggests that our ‘Fight/Flight/Freeze’ (The sympathetic system) is Increased but Also the ‘Rest/digest’ (parasympathetic nervous system) is Decreased. It does seem that our fight/flight system is set to on most of the time. That we have to consciously relax our system. Maybe because of the fact our Rest/Digest system also is malfunctioning. That is just not cool.

his Chinese-Duke collaboration proposed that an overactive stress response system (“enhanced catecholamine tone”) has triggered the neuroinflammation in fibromyalgia (FM), chronic fatigue syndrome (ME/CFS) and similar disorders. No injury was necessary to start the  just a really amped up fight/flight system.


This is exactly what I was curious about- this apparent hyperactive Fight/Fight system I think we may have going on. In this case, they are thinking it is this hyper response that is triggering the neuroinflammation. And, well, could very well be true when you think of all the effects of long-term chronic stress.

Heart variability

One factor that I have wondered about regarding this topic has been research looking at heart variability and fibromyalgia. I actually test my heart variability and most of the time it is extremely poor. There is no reason for it to be but it often is. There has been research to show that with fibromyalgia that is often the case.

heart rate variability (HRV) studies suggest the sympathetic nervous system (“fight or flight”) is hyperactive or always on in FM and ME/CFS. That hyperactivity has made an exploration of the COMT enzyme which breaks down norepinephrine – the driver of SNS activity – a long-standing pursuit. A balky COMT enzyme could lead to high norepinephrine levels and an always on fight or flight system. Other studies have focused on the beta-2 adrenergic receptors that bind to norepinephrine (and epinephrine).


Sympathetic Nervous System – Neuroinflammation 

The Duke/Chinese researchers were intent on determining how sympathetic nervous system activation could lead to immune activation, long-term neuroinflammation and chronic pain.

They turned up the dial on the sympathetic nervous system by inhibiting the COMT enzyme that breaks down the norepinephrine and then they waited and watched. Fourteen days later, their subjects – rodents – were demonstrating signs of widespread pain.


Good thing to remember and note about this study is that it is a rat study. But, they are trying to show that prolonged fight/flight/freeze activation could, in fact, leads to neuroinflammation and chronic pain itself. (not that chronic pain leads to the heightened fight/flight response). So which came first? Chronic stress leading to pain. Chronic pain leading to chronic stress?

The basics of the research:

  • Numerous studies demonstrate sustained activation of the sympathetic nervous system (SNS) can result in increased pain sensitivity
  • The Duke/Chinese researchers amped up the SNS system of rodents by inhibiting the activity of an enzyme called COMT that breaks down norepinephrine (the main driver of SNS activity).
  • It took from 2-3 weeks for a chronic pain state and signs of neuroinflammation to appear (this state of affairs remained after the sympathetic nervous system activation was turned off.
  • That suggests that while the sympathetic nervous system (SNS) activation was needed to trigger a chronic pain state, something else is maintaining it in the brain after that. Something is keeping the ball rolling.
  • The researchers discovered that three cytokines (TNFα, IL-1β, and IL-6) were the driving factor behind the chronic pain state in the brain.
  • Then they were able to stop the pain by inserting a TNF-a blocker called etanercept (Enbrel) into the rodents spinal cords.
  • That may suggest that while the sympathetic nervous system (SNS) activation triggers the pain state, going after the resulting neuroinflammation may be the main factor for treamtment of fibromyalgia.

The treatment used in the study (TNF-a blocker called etanercept -Enbrel) is normally used to treat inflammatory pain conditions, like arthritis and inflammatory bowel disease (IBD), and neuropathic pain conditions. But this was only a rodent study so far. And that was the only drug (Enbrel) the researchers could suggest would work and the method used wouldn’t work on humans.

Healthrising notes:

Nor have the genetic issues with the COMT enzyme or the functioning of the beta adrenergic receptors been completely fleshed out in FM or ME/CFS. Some studies suggest the situation may be complicated by different subsets of patients.

The authors also don’t tell us why the stress response might get lodged on the “on” position long enough to get an immune response in the brain going, nor if people with FM are more susceptible to getting neuroinflammation started in the first place.


There is always a subset fibromyalgia problem in research for sure. And the genetic research isn’t quite there yet, as they say. But, I agree… how did our Fight/Flight/Freeze response get stuck on the ON state? Let alone long enough for this reaction to occur and for neuroinflammation to happen and lead to chronic pain? Genetics? Or maybe as new research suggests some sort of auto-immune trigger?

What I find most fascinating about this research is in Healthrisings conclusion as well:

Still, the study presents a pretty compelling picture of how an upregulated fight or flight system could lead to a chronic pain state maintained in the brain by immune activity. It suggests that pain state may be triggered by receptor activation in the body, not the central nervous system, and that a successful treatment needs to target both the neuroinflammation in the brain and the SNS activation in the body.


With chronic pain, we get a prolonged chronic stress response and our flight/fight/freeze response is constantly On. What is interesting about this fibromyalgia research (And M.E. as well) is that an out of whack unregulated fight/fight/freeze response could actually Lead to the chronic pain in the first place and then maintained by the brain. That treatment has to involve treatment of the neuroinflammation and the sympathetic nervous system (SNS) activation.

It is hard to say if this theory is right or not. What we do know is that chronic pain is a chronic stress state of being either way. Regardless of what triggered chronic pain with fibromyalgia, it is similar to all chronic pain in the resulting chronic stress state. That we do have to always deal with stress management as a result. That we have to be aware of how our body is responding to stress- as in our particular fight/flight/freeze responses (see my first post for possible responses you may be having due to pain) so that we know when to manage them and what self-management techniques would work for us.

Read: Chronic stress and the body

Fight Flight Response mini-series posts

Getting to know your Fight, Flight and Freeze response
Ways to calm your fight or flight response

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