Negative Feedback Loops and Fibromyalgia


Negative feedback loops can best be described as chain reactions of events that have negative consequences. Each event is fed by the previous one in an overall circular pattern or downward spiral, and the cycle continues until something occurs to terminate it. With fibromyalgia, research appears to indicate that negative feedback loops of varying intensity can play a key role for many patients (though clearly more specific research is needed and the functioning of negative feedback loops in fibromyalgia can vary from individual patient to patient). Many of the comorbid conditions frequently associated with fibromyalgia – including anxiety, depression, stress, and sleep disorders – can be exacerbated by negative feedback loops that can vary in intensity. Not only do these negative feedback loops influence the condition itself, but they also can cause a particular symptom to lead to yet another one (for instance, heightened stress that leads to increased disturbances in sleep). For the fibromyalgia patient, a common feature across all of these negative feedback loops is the chronic pain that characterizes fibromyalgia itself.

Negative feedback loops can function to a degree in all individuals. Anxiety can feed depression which can impede normal sleep and lead to fatigue which may further feed the anxiety. But in most individuals these types of loops will be temporary as the external factors which may have triggered the anxiety or stress to begin with will be resolved and in the absence of the initial triggering factor to fuel or drive the negative loop it will fade. Typically, health related negative feedback loops require some external factor to function as a catalyst in order to drive the loop on an ongoing basis. This phenomenon is related to common terms like “it’s making me sick with worry” as indeed may be the case! With fibromyalgia,  the syndrome itself can provide the ongoing catalyst that can foster multiple aspects of an ongoing negative feedback loop. 

Note that negative feedback loops are not a factor for all patients,  and the means by which they manifest themselves will likely be different not just from patient to patient but will change over time and be fluid for each individual. External factors including treatment initiatives (can be good or bad – side effects, interactions, etc),   environmental factors (weather – chemical sensitivity – events) and the frequency or intensity of a fibromyalgia flare-up can play key roles in both the development and continuation of negative feedback loops. The deep persistent pain that characterizes fibromyalgia frequently serves as an ongoing catalyst to help perpetuate negative feedback loops that otherwise would resolve themselves.

Examples of Negative Feedback Loops in Fibromyalgia

While it is not possible to point to any established pattern of causal symptoms that can be demonstrated as consistent within Fibromyalgia, there are a number of common symptomatic problems that frequently present in combination and for which research (not just Fibromyalgia specific) has indicated possible links.

Depression and Anxiety

Fibromyalgia patients who suffer from depression and anxiety frequently modify their behaviors in response to the symptoms they experience from their depression, such as self-imposed isolation and markedly decreased activity. Research shows that non-depressed fibromyalgia patients are much more active than their depressed counterparts. Furthermore, research also demonstrates that physical activity is extremely useful in providing relief from the pain and fatigue associated with fibromyalgia. Therefore, depressed fibromyalgia patients can easily fall into a negative feedback loop that perpetuates and worsens their pain.

Studies conducted in fibromyalgia patients with psychiatric disorders have shown that those with anxiety disorder and mood disorders exhibit more symptoms of their diseases, including greater numbers of tender points and decreased activity than those without anxiety, mood disorders, and depression (Thieme et al., 2004; Ross et al., 2010; Maletic & Raison, 2009). Consider this example: a woman with both fibromyalgia and depression begins an exercise regimen that initially provides some relief from her persistent fibromyalgia pain. A few weeks into the program, she discontinues the regimen, which was providing relief from her pain, due to a pulled muscle. As her period of inactivity lengthens, her pain worsens and causes her depression to become worse as well. This negative feedback loop continues until she seeks modified treatment for her depression or is able to resume the physical activity regimen (which over time provides some lessening of pain).

As illustrated by the previous examples, depression can indirectly modify the course of fibromyalgia and affect pain status if it is not treated appropriately, thereby continuing the cycle of pain and causing fibromyalgia patients to live less active and fulfilling lives. 

Another example can be examined through the lens of anxiety disorder. An individual who suffers from anxiety may become anxious prior to speaking in front of a large crowd. When she notices her anxiety building up, she may also notice an increase in her heart rate and notice that she is breathing rapidly. These symptoms work together to further increase her anxiety, by causing her to feel as if she will hyperventilate and pass out. This negative feedback loop – characterized by fear and loss of control – will continue until something occurs to stop it, such as the woman breathing into a paper bag to calm her breathing.


Research is emerging to support the potential role of stress in not only the development of fibromyalgia, but also as a perpetuator of  the persistent pain and fatigue that characterize the syndrome by way of negative feedback loops.

Survey data from fibromyalgia patients has demonstrated that various personal and social resources (including self-esteem, self-efficacy, and available social support) are predictive of an individual’s level of perceived stress. Perceived stress, as a result, also appears to be related to the impact of fibromyalgia. For example, individuals who are constantly under stress and who have a reduced capacity to cope (as a result of lacking personal and social resources), experience greater levels of subsequent stress and increased fibromyalgia impact. This increased impact of fibromyalgia creates additional stress with which the individual may have difficulty coping, thus creating a negative feedback loop that perpetuates the fibromyalgia pain (Gonzalez-Ramirez et al., 2011).

Gupta and Silman (2004) have investigated the biologic basis for negative feedback loops in fibromyalgia, in particular the interactions between the neurological and endocrine systems. The proper functioning of these two systems relies on their ability to work together, by producing and exchanging various hormones and chemicals. These researchers suggest that chronic stress may lead to abnormalities in the levels of these chemicals and hormones, which in turn contribute to increased pain and fatigue. The persistent pain and fatigue create more stress for the fibromyalgia patient, thereby perpetuating the chemical and hormonal imbalance, and continuing the cycle.

A more recent review article by Martinez-Lavin (2007) expands on this understanding of the central nervous system’s role in the body’s regulation and perception of pain. In his paper, the author discusses a similar scenario describing the association between stress and fibromyalgia pain. He suggests that numerous factors (environmental, genetic, and stress-related) work together to place the body in a sort of “hyperactive” mode. This hyperactive mode opens the nervous system up to potential changes in structure and function, which can thereby result in the excess pain of fibromyalgia. As this pain persists and causes stress on the fibromyalgia, it prevents the body (through negative feedback loops) from rebounding from the hyperactive state (Martinez-Lavin, 2007).

Sleep Disturbances

Research also supports a negative and cyclical association between fibromyalgia symptom severity, sleep disturbances, and pain (Edinger et al. 2005; Miro et al., 2011; Nicassio et al., 2002). Such a negative feedback loop plays a prominent role in the lives of fibromyalgia patients, as sleep disturbances are often a defining symptom of fibromyalgia.

Take the example of a woman newly-diagnosed with fibromyalgia who cannot treat her pain to a manageable level. Due to the extreme pain she experiences, she is unable to get comfortable at bedtime and finds that it often takes hours for her to fall asleep. Once she is finally asleep, she is awakened numerous times throughout the night with leg cramps and hip pain. Because she is unable to get refreshing sleep, she wakes up fatigued, sore, and stiff. Enduring the cycle night after night feeds a sense of hopelessness for the woman, and contributes to the eventual onset of depression.

In this example of a negative feedback loop, daytime pain compromises sleep quality by making restful sleep difficult to achieve and maintain. Furthermore, the constant sleep deprivation and inadequate sleep quality worsens the pain associated with fibromyalgia and results in other symptoms that are besieged with their own negative feedback loops, such as fatigue, anxiety, and depression.



1.        Thieme K, Turk DC, Flor H. Comorbid depression and anxiety in fibromyalgia syndrome: relationship to somatic and psychosocial variables. Psychosom Med. 2004;66:837-844.

2.        Ross RL, Jones KD, Ward RL, Wood LJ, Bennett RM. Atypical depression is more common than melancholic in fibromyalgia: an observational cohort study. BMC Musculosket Disord. 2010;11:120-133.

3.        Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009;14:5291-5338.

4.        Edinger, J. D., Wohlgemuth, W. K., Krystal, A. D., Rice, J. R. Behavioral insomnia therapy for fibromyalgia patients: A randomized clinical trial. Arch Int Med. 2005;165:2527–2535.

5.        Miro E, Martinez MP, Sanchez AI, Prados G, Medina A. When is pain related to emotional distress and daily functioning in fibromyalgia syndrome? The mediating roles of self-efficacy and sleep quality. Br J Health Psych. 2011;16:799-814.

6.        Nicassio PM, Moxham EG, Schuman CE, Gevirtz RN. The contribution of pain, reported sleep quality, and depressive symptoms to fatigue in fibromyalgia. Pain. 2002;100(3):271-279.

7.        Gupta A, Silman AJ. Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link. Arthritis Res Ther. 2004;6(3):98-106.

8.     Martinez-Lavin M. Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia. Arthritis Res Ther. 2007;9(4):216.s

9.     Gonzalez-Ramirez MT, Garcia-Campayo J, Landero-Hernandez R. The role of stress transactional theory on the development of fibromyalgia: a structural equation model. Actas Esp Psiquiatr. 2011;39(2):81-87.

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