title: Activation of extracellular signal-regulated kinase in the trigeminal ganglion following both treatment of the dura mater with capsaicin and cortical spreading depression.
abstract: Extracellular signal-regulated kinase (ERK) is known to be phosphorylated after exposure to noxious stimuli. In this study, we investigated the response in the dura mater to nociceptive stimulation, which is thought to be responsible for the pathogenesis of headaches, including migraines. We also examined the level of ERK phosphorylation in the trigeminal ganglion following cortical spreading depression (CSD), which is thought to play an important role in migraine pathophysiology. Western blot and immunohistochemical analyses showed a significant increase in the ERK phosphorylation levels 3 min following an application of 10mM capsaicin to the dura mater. This increase was inhibited after an application of the TRPV1 antagonist capsazepine or a MEK inhibitor. An immunohistochemical analysis revealed that most of the small-sized trigeminal ganglion neurons with TRPV1-immunoreactivity that innervate the dura mater exhibited pERK-immunoreactivity, suggesting that these neurons had responded to nociceptive stimulation. CSD increased the level of ERK phosphorylation 30 min after its elicitation, and this response was inhibited by a prior intraventricular administration of TRPV1 antagonist. These results indicate that CSD can activate dural TRPV1 to send nociceptive signals to the trigeminal system, and they provide important clues regarding the relationship between CSD and the trigeminovascular system.
authors: Department of Neurology, School of Medicine, Keio University, Japan. Electronic address: iwashita@a6.keio.jp.
authors: Tatsuo
authors: T
authors: Iwashita
authors: Toshihiko
authors: T
authors: Shimizu
authors: Mamoru
authors: M
authors: Shibata
authors: Haruki
authors: H
authors: Toriumi
authors: Taeko
authors: T
authors: Ebine
authors: Megumi
authors: M
authors: Funakubo
authors: Norihiro
authors: N
authors: Suzuki
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D013181:Cortical Spreading Depression; D004388:Dura Mater / Q000187:drug effects / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D059225:Nociception / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000201:enzymology*
chemical_list: D018689:Sensory System Agents; D048049:Extracellular Signal-Regulated MAP Kinases; D002211:Capsaicin
keywords: Cortical spreading depression; ERK; TRPV1; Trigeminal ganglion