Are Headaches Associated With Low Dopamine or Serotonin?

Researchers have observed low brain levels of serotonin and hypersensitivity to dopamine in subjects with primary headaches, headaches that do not result from another medical condition. Drugs that raise the brain’s levels of serotonin and balance its levels of dopamine have furthermore been effective as a treatment of primary headache. These findings suggest that headaches may be associated with an imbalance in the brain’s dopamine or serotonin levels.

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The brain does not contain neurons that are sensitive to pain. So, headaches do not result from brain pain. They arise when pressure activates the nerves sensitive to pain in the tissues covering the brain or in the muscles and blood vessels around the face, neck and scalp. There are three types of headaches -- tension, cluster and migraine headaches. A tension of muscles around the scalp, face or neck can give rise to tension headaches, while a state of neuronal hyperexcitability in the cerebral cortex is a likely trigger of cluster and migraine headaches.


The neurotransmitter serotonin helps control pain, sleep, mood, sexual behavior and dilation and constriction of the blood vessels. Fluctuations in the brain’s levels of serotonin are strongly associated with chronic tension, cluster and migraine headaches 1. When muscle tensions or hyperexcitatory neuronal state stimulates the trigeminal nerve, a sensory cranial nerve, it releases a number of chemical substances. These substances cause an inflammation of the trigeminal nerve. When the inflammation and blood vessels interact, the blood vessels dilate, which causes pain. In individuals who don’t suffer from headaches, serotonin can help prevent dilation. People who suffer from severe headaches don’t have this regulatory system in place.


Dopamine is a neurotransmitter that is responsible for muscle contraction, motivation, energy levels, cognition and memory. Individuals who suffer from migraines commonly have a hypersensitivity to dopamine. When dopamine overstimulates dopamine receptors, this can cause symptoms of migraine, such as:

  • hyperactivity
  • irritability
  • nausea
  • vomiting
  • yawning
  • hypotension

While a cluster or tension headache can come on merely as a result of low levels of serotonin, a full-blown migraine headache may require both low levels of serotonin and hypersensitivity to dopamine.

Serotonin and Dopamine Treatments

Further evidence for the role of serotonin and dopamine in headaches comes from the standard treatment of migraine. Selective serotonin reuptake inhibitors, or SSRIs, are a class of second-generation antidepressant drugs that target serotonin specifically. They prevent the serotonin transporter from transporting serotonin back into the neurons. This increases the availability of serotonin at the synapses, the junctions between neurons. SSRIs are not as effective in the treatment of migraine as conventional migraine medicine, such as the first-generation antidepressants tricyclics and monoamine oxidase inhibitors, or MOAs. As both tricyclics and MOAs control the brain’s levels of dopamine and serotonin, the fact that these drugs are more effective than SSRIs suggests that a serotonin and dopamine imbalance contributes to migraine headaches.