Mast cell degranulation activates a pain pathway underlying migraine headache.
Intracranial headaches such as that of migraine are generally accepted to be mediated by prolonged activation of meningeal nociceptors but the mechanisms responsible for such nociceptor activation are poorly understood. In this study, we examined the hypothesis that meningeal nociceptors can be activated locally through a neuroimmune interaction with resident mast cells, granulated immune cells that densely populate the dura mater. Using in vivo electrophysiological single unit recording of meningeal nociceptors in the rat we observed that degranulation of dural mast cells using intraperitoneal administration of the basic secretagogue agent compound 48/80 (2 mg/kg) induced a prolonged state of excitation in meningeal nociceptors. Such activation was accompanied by increased expression of the phosphorylated form of the extracellular signal-regulated kinase (pERK), an anatomical marker for nociceptor activation. Mast cell-induced nociceptor interaction was also associated with downstream activation of the spinal trigeminal nucleus as indicated by an increase in c-fos expression. Our findings provide evidence linking dural mast cell degranulation to prolonged activation of the trigeminal pain pathway believed to underlie intracranial headaches such as that of migraine.
Levy
Dan
D
Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Room 856, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. dlevy1@bidmc.harvard.edu
Burstein
Rami
R
Kainz
Vanessa
V
Jakubowski
Moshe
M
Strassman
Andrew M
AM
D000344:Afferent Pathways / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology*; D004388:Dura Mater / Q000276:immunology / Q000378:metabolism; D004594:Electrophysiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D008881:Migraine Disorders / Q000276:immunology* / Q000378:metabolism; D009619:Nociceptors / Q000201:enzymology / Q000276:immunology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014279:Trigeminal Nucleus, Spinal / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D003189:p-Methoxy-N-methylphenethylamine; D048049:Extracellular Signal-Regulated MAP Kinases