Norepinephrine in Fibromyalgia & Chronic Fatigue Syndrome

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According to the findings of one study, the adrenal hormone norepinephrine may be responsible for the body pain associated with FMS. The study’s conclusion: Fibromyalgia patients have norepinephrine-evoked pain. This finding supports the hypothesis that fibromyalgia may be a sympathetically maintained pain syndrome

Norepinephrine (NE)

Norepinephrine (NE) is both a neurotransmitter and a hormone. Neurotransmitters send messages from one cell to another in your brain and spinal cord. Hormones help regulate things around your body. Also called noradrenaline, NE plays a key role in the “fight or flight” response by spiking your heart rate and blood pressure when your body believes it’s in danger. NE is similar to adrenaline and many experts believe it helps determine your basic levels of stimulation and arousal. It’s is linked to anxiety and depression. High levels are associated with feelings of joy, and sometimes euphoria.


When the core body temperature is cooled below approximately 37 degrees Celsius (98.6 F), special mechanisms are set into play to conserve the heat that is already in the body, and still other mechanisms are set into play to increase the rate of heat production.

One of the first effects is intense vasoconstriction of the skin vessels over the entire body. The posterior hypothalamus strongly activates the sympathetic nervous signals to the skin blood vessels, and intense vasoconstriction occurs throughout the body. This vasoconstriction obviously prevents the conduction of heat from the internal portions of the body to the skin.

Norepinephrine has vasoconstrictor effects in almost all vascular beds of the body, and epinephrine has similar effects in most, but not all, beds.

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A Study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases

In a study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and co-funded by the NIH’s Office of Research on Women’s Health, lead investigator Luc Jasmin, MD, PhD, examined the role of noradrenaline (norepinephrine) in chronic pain by studying mice lacking this neurotransmitter throughout their bodies and rats lacking it in their brains and spinal cords. Some researchers hypothesize that fibromyalgia is somehow linked to a lack of noradrenaline, yet medications that act on noradrenaline have only been a limited success for treating chronic pain syndromes.

Mice was used as a model

To better understand the role of noradrenaline in chronic pain, Dr. Jasmin and a team of researchers studied pain response in rodents that lacked the hormone and neurotransmitter. The team used mice that had been genetically altered to lack noradrenaline before birth. The team also used adult rats, giving them a drug that wipes out the noradrenaline-producing cells in the central nervous system.


Both the mice and the rats had lower pain thresholds than animals with normal noradrenaline levels. The effect of treatment on pain thresholds was less pronounced for the rats than the mice. This result may be due to the fact that the rats’ noradrenaline levels were depleted later in life, as adults – a scenario that more closely mimics what might occur in humans than the mouse model. (Human beings are rarely born without noradrenaline. It is necessary for fetal development.)

In rats, as in people with fibromyalgia, drugs designed to act on noradrenaline had little effect on pain, suggesting that although a noradrenaline deficit probably plays a role in chronic pain, other chemical anomalies in pain circuits also may play a critical role in the condition.

Norepinephrine Dysfunction

Neurotransmitter function is complicated and neurotransmitters work with each other in a complex way we’re just beginning to understand. Still, experts have been able to associate different neurotransmitter imbalances with certain conditions and symptoms and find some ways to change their activity. NE activity takes place in several areas of your brain. Each brain region uses NE differently, and they each contain several different kinds of receptors that also influence how NE is used.

NE dysfunction is associated with these symptoms:

Loss of alertness
>Memory problems (brain fog or fibro fog)
>Lack of arousal and interest

We don’t yet know why NE is dysfunctional in people with FMS and ME/CFS. Constant fear and anxiety are known causes of impaired NE function, so people who live with a lot of those emotions may be especially at risk for developing these illnesses.

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Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Medications that inhibit the reuptake of norepinephrine and serotonin  (which is another neurotransmitter) are called serotonin-norepinephrine reuptake inhibitors (SNRIs). By inhibiting the reuptake of these two neurotransmitters, SNRIs essential increase the levels of norepinephrine and serotonin in the brain. Serotonin makes a person feel good and norepinephrine improves energy and attentiveness. SNRIs have been found to be effective in treating mood disorders like depression, bipolar disorder, and anxiety disorders. They are also sometimes prescribed for chronic pain and fibromyalgia.

SNRIs for Treating Mood Disorders

The SNRIs approved for use in major depression include Cymbalta (duloxetine), Effexor (venlafaxine) and Pristiq (desvenlafaxine), but there are others approved for other illnesses as well. Although no antidepressants, including SNRIs, have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of bipolar disorder, they are sometimes prescribed as part of an individual treatment plan.

As a hormone, norepinephrine is released into the bloodstream by the adrenal glands and works alongside adrenaline (also known as epinephrine) to give the body sudden energy in times of stress, known as the “fight or flight” response.

Effexor (Venlafaxine)

Effexor was the first SNRI to be approved in the United States in 1993. It has been approved by the FDA for depression, panic disorder, social phobia, and generalized anxiety disorder (GAD). Effexor inhibits the reabsorption of serotonin quite a bit more than it does norepinephrine.

Reference: Verywell Health

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