Stress Responses in the Brain

The way that the brain responds to stress may be a factor in the development of fibromyalgia in individuals with specific genetic predispositions.  Stress, particularly long or intensive stress, can actually change the sensitivity of the brain to different chemicals, particularly the chemicals that trigger stress responses and relaxation. Over time and with higher levels of stress hormones the brain neurotransmitters and pathways can become altered, leading to changes in stress responses and even in the way that the entire body responds to stress.

A Normal Stress Response

When the body and brain perceive a possible threat, which may be real or just a misinterpretation of the environment, the brain and body prepare to either flee, fight or, in some cases, to freeze. The majority of time the body is going to either fight or flee, which means that all systems, particularly the large muscle groups, the cardiovascular and respiratory systems, and the limbic part brain, all have to be highly active and completely engaged. This is controlled by the sympathetic nervous system or the SNS.

The SNS controls the internal organs of the body, shutting some down and activating others to allow the greatest energy use in the organs needed to maintain safety. The adrenal glands release cortisol, the stress hormone, which in turn triggers a variety of different chemicals and hormones through the body. At the same time the individual neurons in the body flood the system with acetylcholine, which in turn triggers the release of noradrenaline. This triggers the adrenal glands to release adrenaline, which may also be called epinephrine, which acts on all cells in the body, including the brain.

When the adrenaline reaches the central nervous system, which includes the brain and the nerves that make up the spinal cord, several immediate changes occur. This includes enhancing the corticosteroid receptors, which uptake the cortisol in the hippocampus, amygdala and the prefrontal cortex. Repeated overstimulation or chronic stimulation of the hippocampus can change the response of the brain to serotonin, which helps to return the brain to normal activity. 1 Once this is activated the brain is more sensitive to all hormones since the protective barrier, known as the blood brain barrier, decreases its functioning. The brain is literally doused in cortisol and other corticosteroids which trigger the overstimulation of the receptors in the hippocampus, amygdala and the prefrontal cortex.

These over-stimulated cells release calcium, which helps to speed up the transmission of the messages sent from the areas of the brain that manage the flight or flight response. This hypersensitivity to the neurological impulses, if sustained over long periods of time, changes the functioning of the cells and can even lead to premature cell death.

In a normal response to stress, the body responds to the high levels of cortisol and noradrenaline by activating the parasympathetic system. This system triggers the endocrine glands, specifically those of the hypothalamic-pituitary-adrenal (HPA) axis, to stop producing the corticosteroids; it is actually the off switch, which returns the system to normal. In addition the hippocampus of the brain also controls the off switch for the production of cortisol, which is triggered when blood concentrations reach a particular level.

When there is elevated cortisol for long periods of time the sensitivity of the hippocampus decreases and, in new studies, this also happens as people age. In studies of deceased individuals between 79 and 101 years of age it was found that both calcium and magnesium levels were significantly higher than in younger individuals, which may be due to stress. 2This cycle of high cortisol causing hippocampus cell death and lack of ability of the hippocampus to signal the adrenal glands to stop producing cortisol is known as degenerative cascade.

High Stress Levels on the Brain 

High levels of hormones and specific chemicals in the brain due to hyperstimulation of the HPA axis and sympathetic nervous system cause significant changes to the brain’s structure and response to hormonal levels. One major change noted in people with stress disorders is a change in long-term potentiation, which is the way in which cells are able to transmit information. This is the method by which learning occurs in the brain, as well as the way in which the brain stores and retrieves memories and information.  It is particularly problematic when the hippocampus is affected, as lack of message transmission prevents the shut-down of the sympathetic nervous system triggers that lead to increased stress hormones in the brain.

Other changes noted in the brain include a decrease in the neuroplasticity of the brain. The neuroplasticity is the ability of the brain to respond and change based on the environment, injury or infection. This is done by the ability of the brain to develop new and more productive neurological pathways to provide information from one area of the brain to the other. When neuroplasticity is compromised, these new pathways are not created, leading to the inability of the brain to change and respond in effective ways to the environment, including the flooding of the brain by the flight or flight hormones.

Adrenal Fatigue

Another concern of chronic stress is the development of a condition known as adrenal fatigue. The symptoms of adrenal fatigue tend to mimic those of fibromyalgia including fatigue, mental confusion and fogginess and sleep changes. With adrenal fatigue you are more likely to feel better in the late evening but have great difficulty in getting up in the morning. Despite sleeping for long periods of time you still feel exhausted and unable to complete daily tasks. Research into the connection between the actions of the HPA and the development of chronic fatigue syndrome indicate that there may be a dysregulation present due to stress intolerance and pain hypersensitivity. 3

Adrenal fatigue occurs when the body is constantly under stress and the sympathetic nervous system is demanding that the adrenal glands produce cortisol. Over time the body simply cannot respond, again leaving the body out of balance and creating changes to the chemistry of the brain that, if sustained, can change the neurological pathways that control the responses to stress.

Further research into the role of adrenal fatigue and the development of fibromyalgia is needed to determine if there is a link between fibromyalgia, chronic fatigue syndrome and other pain syndromes, and the overstimulation of the HPA.


1 Joels, M. (2008). Functional actions of corticosteroids in the hippocampus. European Journal of Pharmacology , 312-321.

2 Tohno, Y., Tohno, S, Ongkana, T., et al. (2010). Age-Related Changes of Elements and Relationships Among Elements in Human Hippocampus, Dentate Gyrus, and Fornix . Biological Trace Element Research , 42-52.

3 van Houdenhove, B., van den Eede, F., & Luyten, P. (2009). Does hypothalamic–pituitary–adrenal axis hypofunction in chronic fatigue syndrome reflect a ‘crash’ in the stress system? Medical Hypotheses , 701-705.

This article was originally published on July 11, 2012 and last revision and update of it was 9/7/2015