Where Does Migraine Nausea Originate? A PET Scan Study

Patient Expert
Medically Reviewed

Not only is nausea a common symptom of migraine, it's often quite severe. As with other symptoms, why it occurs has been a mystery. A new _ study_ offers new insights on the origin of nausea during a migraine.

The Study:

Study Background:

"Nausea is a common and disabling symptom of migraine. The origin of nausea is not well understood although functional connections between trigeminal neurons and the nucleus tractus solitarius may explain occurrence of nausea with pain. However, nausea occurs as a premonitory (prodrome) symptom in about a quarter of patients, suggesting that a primary brain alteration unrelated to the experience of pain may be the reason for nausea."

Study Methods:

  • Initially, 125 patients were screened.
  • 27 patients satisfied the inclusion criteria and agreed to participate.
  • The most common reasons for non-inclusion were:
    • migraine / headache more than 15 days per month,
    • use of medications that could confuse the results,
    • migraine aura, and
    • patients who were unwilling to participate because of the radiation exposure of PET scans.
  • The 27 participants received a nitroglycerin infusion to determine which of them experienced prodrome symptoms followed a delayed headache that resembled the headache of their migraine attacks.
  • 13 participants had prodrome symptoms prior to headache and were selected to have PET scans at least seven days after the first nitroglycerin infusion.
  • The 13 participants were invited for PET scans at least seven days following the screening nitroglycerin infusion. 10 accepted.
  • All patients had been pain-free at least 72 hours before the study PET scans.
  • Nitroglycerin infusions were administered to the 10 participating patients, and they were instructed to carefully record their symptoms.
  • Each participating patient had three scans:
    1. a baseline scan while pain-free,
    2. a scan during their prodrome, and
    3. a scan during the headache phase.

Study Results:

During the scans, three patients experienced nausea during prodrome; 10 did not. The scans were examined for differences between the two groups.

"The results showed activation in rostral dorsal medulla and periaqueductal grey (PAG) in the nausea group, which was absent in the no nausea group. The rostral dorsal medullary area included the nucleus tractus solitarius, dorsal motor nucleus of the vagus nerve and the nucleus ambiguus, all of which are thought to be involved in brain circuits mediating nausea."

Study Conclusion:

The results demonstrate that nausea can occur as a premonitory (prodrome) symptom in migraine, independent of pain and trigeminal activation. This is associated with activation of brain structures known to be involved in nausea. We conclude that nausea is a centrally driven symptom in migraine.

Study Limitations:

"It needs to be emphasized that studying nausea in migraine is very difficult, because patients are lying immobilized in the scanner and nausea potentially carries the risk of vomiting with aspiration. No neuroimaging study has specifically addressed nausea in migraine to date. We used data where nausea was recorded, although it was not the main outcome of the principal study. The number of patients in this pilot study was small, especially in the nausea group and group sizes are not balanced. However, each patient had three scans in baseline and between one - three scans in the premonitory phase. We have previously used a similar design using nitroglycerin PET with multiple scans in baseline and spontaneous migraine states and found meaningful results with five subjects. Despite the small number in this study, the absence of activation of the NTS and surrounding areas in the no-nausea group and the presence of activation in these areas in the nausea group indicates that these areas are activated when patients experience nausea in the premonitory phase. Also, the results confirmed the a priori hypothesis that these areas would be activated. A drawback of PET studies is the low spatial resolution of the technique, which makes accurate delineation of specific nuclei difficult. Due to the inherent low spatial resolution of PET, and smoothing procedures, we cannot be certain of not missing any activation in smaller structures. Since we have not compared our findings with patients with nausea due to other reasons, we cannot be certain if the results are specific to the premonitory phase of migraine."

Summary and Comments:

This study is a perfect example of how advances in imaging technology have allowed researchers to learn more about migraine. It was also through PET scan that it was shown that a migraine can occur with no vasodilation.

It would be easy to say, "Who cares where the nausea originates. Just make it stop," but finding the origin of nausea accomplishes two major things:

  1. It takes us a step closer to understanding the origin and pathophysiology of Migraine.
  2. It gives researchers more information to develop better, more effective treatments.

The researchers were quite transparent about the limitations of this study. This small study is a good beginning. We now need larger studies and studies that compare these findings with patients with nausea for other reasons.

More about migraine prodrome:


Maniyar, Farooq H.; Sprenger, Till; Schankin, Christoph; Goadsby, Peter J. "The origin of nausea in migraine A PET study. The Journal of Headache and Pain 2014, 15:84.

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