Document Detail


Vascular extracellular signal-regulated kinase mediates migraine-related sensitization of meningeal nociceptors.
MedLine Citation:
PMID:  23447360     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To examine changes in the response properties of meningeal nociceptors that might lead to migraine pain and examine endogenous processes that could play a role in mediating them using a clinically relevant model of migraine triggering, namely infusion of the nitric oxide (NO) donor nitroglycerin (NTG).
METHODS: Single-unit recordings made in the trigeminal ganglion of rats were used to test changes in the activity and mechanosensitivity of meningeal nociceptors in response to administration of the migraine trigger NTG or another NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) at doses relevant to the human model of migraine headache. Immunohistochemistry and pharmacological manipulations were used to investigate the possible role of meningeal vascular signaling in mediating the responses of meningeal nociceptors to NO.
RESULTS: Infusion of NTG promoted a delayed and robust increase in the mechanosensitivity of meningeal nociceptors, with a time course resembling the development of the delayed migraine headache. A similar sensitization was elicited by dural application of NTG and SNAP. NTG-evoked delayed meningeal nociceptor sensitization was associated with a robust extracellular signal-regulated kinase (ERK) phosphorylation in meningeal arteries. Pharmacological blockade of meningeal ERK phosphorylation inhibited the development of NTG-evoked delayed meningeal nociceptor sensitization.
INTERPRETATION: The development of delayed mechanical sensitization evoked by the migraine trigger NTG is potentially of great importance as the first finding of a neurophysiological correlate of migraine headache in meningeal nociceptors. The arterial ERK phosphorylation and its involvement in mediating the NTG-evoked delayed sensitization points to an important, yet unappreciated, role of the meningeal vasculature in the genesis of migraine pain.
Authors:
XiChun Zhang; Vanessa Kainz; Jun Zhao; Andrew M Strassman; Dan Levy
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-06-17
Journal Detail:
Title:  Annals of neurology     Volume:  73     ISSN:  1531-8249     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-07-22     Completed Date:  2013-09-23     Revised Date:  2014-06-18    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  741-50     Citation Subset:  IM    
Copyright Information:
© 2013 American Neurological Association.
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MeSH Terms
Descriptor/Qualifier:
Animals
Extracellular Signal-Regulated MAP Kinases / physiology*
Male
Meninges / blood supply*,  drug effects,  enzymology*
Migraine Disorders / chemically induced,  enzymology*
Nitric Oxide Donors / toxicity
Nociceptors / drug effects,  enzymology*
Rats
Rats, Sprague-Dawley
Trigeminal Ganglion / drug effects,  enzymology
Grant Support
ID/Acronym/Agency:
(AA020305/AA/NIAAA NIH HHS; NS032534/NS/NINDS NIH HHS; NS061116/NS/NINDS NIH HHS; NS077882/NS/NINDS NIH HHS; R01 NS046502/NS/NINDS NIH HHS; R21 AA020305/AA/NIAAA NIH HHS; R21 NS061116/NS/NINDS NIH HHS; R21 NS077882/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Nitric Oxide Donors; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases
Comments/Corrections

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