PT  - JOURNAL ARTICLE
AU  - Xi-Chun Zhang
AU  - Andrew M. Strassman
AU  - Rami Burstein
AU  - Dan Levy
TI  - Sensitization and Activation of Intracranial Meningeal Nociceptors by Mast Cell Mediators
AID  - 10.1124/jpet.107.123745
DP  - 2007 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 806--812
VI  - 322
IP  - 2
4099  - http://jpet.aspetjournals.org/content/322/2/806.short
4100  - http://jpet.aspetjournals.org/content/322/2/806.full
SO  - J Pharmacol Exp Ther2007 Aug 01; 322
AB  - Intracranial headaches such as migraine are thought to result from activation of sensory trigeminal pain neurons that supply intracranial blood vessels and the meninges, also known as meningeal nociceptors. Although the mechanism underlying the triggering of such activation is not completely understood, our previous work indicates that the local activation of the inflammatory dural mast cells can provoke a persistent sensitization of meningeal nociceptors. Given the potential importance of mast cells to the pain of migraine it is important to understand which mast cell-derived mediators interact with meningeal nociceptors to promote their activation and sensitization. In the present study, we have used in vivo electrophysiological single-unit recording of meningeal nociceptors in the trigeminal ganglion of anesthetized rats to examine the effect of a number of mast cell mediators on the activity level and mechanosensitivity of meningeal nociceptors. We have found that that serotonin (5-HT), prostaglandin I2 (PGI2), and to a lesser extent histamine can promote a robust sensitization and activation of meningeal nociceptors, whereas the inflammatory eicosanoids PGD2 and leukotriene C4 are largely ineffective. We propose that dural mast cells could promote headache by releasing 5-HT, PGI2, and histamine. The American Society for Pharmacology and Experimental Therapeutics