Stress has been known to be deeply associated with several conditions including fibromyalgia. Fibromyalgia is a widespread spontaneous pain syndrome that affects millions worldwide.

Stress is commonly defined as a threat to the homeostasis, stability or balance in an organism.

Stress could be physical (biological stress), or emotional (psychosocial stress).

What happens when an organism faces stress?

Whenever an organism faces stress, the genetically determined neuronal, hormonal and behavioural responses are activated that aim to restore the original state or balance.

Stress response is controlled by two interconnected systems:-

• locus coeruleus-norepinephrin (LC-NE) axis
• hypothalamo-pituitary-adrenal (HPA) axis

These two axes are stimulated by corticotropin-releasing hormone (CRH) secreted by the hypothalamus, the amygdala, and other brain structures.

The LC-NE axis mainly mediates the acute or immediate stress response while preparing the organism for ‘fight or flight’. The HPA axis deals with long term stressors.

Stress and pain response

Stress is deeply connected to pain and several players in this phenomenon include CRH, cortisol and catecholamines that act along with the immune system as well as the endogenous opioid system that modulate pain.
 

In the brain there are endogenous or naturally occurring chemicals or opioids that modulate pain sensation and pain response.

Immediate stress response thus produces alleviation of pain but chronic stress may have the opposite effect, both mediated by CRH.

As the sympathetic activity is diminished, the pain sensitivity rises. This is one of the keystones in the pathology of fibromyalgia.

Stress also leads to neuroinflammation and neuroimmune activation involving pro-inflammatory cytokines such as IL-1, IL-6 and TNF. These are all mediators of pain.

Physical and psychosocial stress and fibromyalgia

Studies have shown that physical stress such as painful injury, chronic physical overuse, infections etc. could lead to development of fibromyalgia.

Other conditions that are included in the affective spectrum disorder including major depressive disorder and generalized anxiety disorder are also associated with stress and fibromyalgia.

Anxiety for example may play a perpetuating role in fibromyalgia by increasing irritability, muscle tension, pain-related fear – avoidance behaviour, higher pain intensity, more tender points, more fatigue and disability.

Alteration of the axes

Alteration of the sympathetic nervous system has been noted in the pathology of fibromyalgia. This could be the result of LC-NE axes under activity that blunts the sympathetic response. This results in drop in blood pressure and decreased neuropeptide Y.

The HPA axis is also altered in fibromyalgia. These patients have a delayed ACTH plasma peak when stimulated by CRH with normal cortisol levels.

Results from studies reveal that fibromyalgia patients have an impaired ability to activate the HPA axis especially at the pituitary level that leads to an inadequate cortisol response to stress or normal activities of daily living.