Norepinephrine in Fibromyalgia & Chronic Fatigue Syndrome

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.

Illustration of a norepinephrine molecule.
PASIEKA / Getty Images

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 is linked to anxiety and depression. High levels are associated with feelings of joy, and sometimes euphoria.

Since joy and euphoria aren't exactly typical of fibromyalgia (FMS) and chronic fatigue syndrome (CFS or ME/CFS), it's no surprise that research suggests most people with these conditions have either low NE levels or that our bodies don't use NE efficiently.

The connection to low NE is more definite in FMS, but a growing body of research shows people with ME/CFS have an imbalance between NE and dopamine, and treatments that make more NE available to the brain are successful for some of us.

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:

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.

Making More NE Available

To make more NE available to your brain, you can take serotonin norepinephrine re-uptake inhibitors (SNRIs), such as Cymbalta (duloxetine) or Savella (milnacipran); or amphetamines, including Adderall (dextroamphetamine), which is often used to treat ADD/ADHD.

Several things that are part of life are generally believed to boost NE levels in your brain, including:

  • Quality sleep (which is difficult for us)
  • Exercise (which is difficult for us)
  • Meeting goals (even small ones!)

Symptoms of High NE Levels

When you take medications that raise your NE levels or activity, you might be told to notify your doctor if you become "too happy." That's because it's a sign of potentially dangerous high NE levels, which can also cause symptoms such as:

  • Worry, anxiety, irritability, and jumpiness
  • Fears of crowds and confined places
  • Impaired concentration
  • Restless sleep
  • Muscle tension or cramps

Many anxiety disorders are associated with too much NE. The effects of several street drugs, including cocaine and illegal amphetamines, stem from increased NE levels and the resulting physical arousal and feelings of elation, which is part of what makes these drugs addictive.

Be sure to include your doctor in any decisions about increasing your NE levels and notify him or her if you experience any symptoms of too much NE.

A Word From Verywell

NE is only one of several neurotransmitters that are believed to be dysregulated in FMS and ME/CFS. Others include:

  • Serotonin
  • Dopamine
  • GABA & glutamate

Each neurotransmitter contributes its own set of symptoms. Some treatments may help regulate more than one, but you may need to work with your doctor to find the combination of treatments that affords you the most relief.

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  1. Montoya A, Bruins R, Katzman M, Blier P. The noradrenergic paradox: implications in the management of depression and anxiety. Neuropsychiatr Dis Treat. 2016;12:541–557. doi:10.2147/NDT.S91311

  2. Chinn S, Caldwell W, Gritsenko K. Fibromyalgia pathogenesis and treatment options update. Curr Pain Headache Rep. 2016;20(4):25. doi:10.1007/s11916-016-0556-x

  3. Pardini M, Cordano C, Benassi F, et al. Agomelatine but not melatonin improves fatigue perception: a longitudinal proof-of-concept study. Eur Neuropsychopharmacol. 2014;24(6):939-944. doi:10.1016/j.euroneuro.2014.02.010

  4. Briley M, Blier P. The noradrenergic symptom cluster: clinical expression and neuropharmacology. Neuropsychiatr Dis Treat. 2011;7(Suppl 1):15–20. doi:10.2147/NDT.S19613

  5. Seki K, Yoshida S, Jaiswal MK. Molecular mechanism of noradrenaline during the stress-induced major depressive disorder. Neural Regen Res. 2018;13(7):1159. doi:10.4103/1673-5374.235019

  6. National Library of Medicine, DailyMed. Cymbalta- duloxetine hydrochloride capsule, delayed release [drug label]. Updated November 3, 2020.

  7. National Library of Medicine, DailyMed. Savella- milnacipran hydrochloride tablet, film coated [drug label]. Updated December 1, 2017.

  8. Rowe PC, Underhill RA, Friedman KJ, et al. Myalgic encephalomyelitis/chronic fatigue syndrome diagnosis and management in young people: a primer. Front Pediatr. 2017;5:121. doi:10.3389/fped.2017.00121

  9. Endocrine Society. Norepinephrine. Updated September 4, 2019.

  10. Arbuck D. Neurobiological and neuropsychiatric mechanisms of fibromyalgia and their implications for treatment. Pain Manag. 2012;5(6).

  11. Rebec GV. Cocaine and amphetamines. eLS. 2012. doi:10.1002/9780470015902.a0000042.pub3