Serotonin Depletion, Cortical Spreading Depression, and Trigeminal Nociception


  • Weera Supornsilpchai MSc,

  • Sompol Sanguanrangsirikul MD,

  • Supang Maneesri PhD,

  • Anan Srikiatkhachorn MD

  • From the Department of Physiology Faculty Medicine (Mr. Supornsilpchai, and Drs. Sanguanrangsirikul and Srikiatkhachorn); and Department of Pathology, Chulalongkorn University, Bangkok, Thailand (Dr. Maneesri).

Address all correspondence to Anan Srikiatkhachorn, Chulalongkorn University, Physiology, Bangkok, Thailand.


Background.—The attack of migraine has been observed to be associated with low level of serotonin (5-HT). Although the mechanism underlying this relationship is still unclear, change in cortical excitability or susceptibility of trigeminal system is a possible explanation.

Objectives.—The aim was to study the effect of 5-HT depletion on the development of cortical spreading depression (CSD) and CSD-evoked trigeminal nociception.

Methods.—Wistar rats were separated into low 5-HT and control groups (eight rats each). 5-HT was depleted by administration of para-chlorophenylalanine, a tryptophan hydroxylase inhibitor. CSD was induced by applying 3 mg of potassium chloride on parietal cortex. Cortical activity was monitored for 1 hour. Trigeminal nociception was determined using number of Fos-immunoreactive (Fos-IR) neurons in trigeminal nucleus caudalis as the indicator.

Results.—Application of KCl led to the development of series of depolarization shift characteristics for CSD. The development of these CSD waves was enhanced in low 5-HT state. The area under curve of each CSD wave and the number of CSD waves occurring within 1 hour were greater in low 5-HT group. No significant change in peak amplitude and duration of CSD wave was observed. The numbers of Fos-IR cells on ipsilateral and contralateral trigeminal nucleus caudalis were significantly greater in the low 5-HT group than those of the controls.

Conclusion.—Our findings indicate that 5-HT depletion enhances CSD-induced trigeminal nociception by increasing the cortical excitability and sensitivity of trigeminal nociceptive system. These findings may provide a better understanding regarding the relationship between low 5-HT and clinical headaches.