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Dynamic sodium imaging at ultra-high field reveals progression in a preclinical migraine model

Abad, Nastarena,b; Rosenberg, Jens T.a; Hike, David C.a,b; Harrington, Michael G.c; Grant, Samuel C.a,b,*

doi: 10.1097/j.pain.0000000000001307
Research Paper

Under the hypothesis that increased extracellular sodium induces sustained neuronal excitability with the onset and progression of migraine, this study evaluates dynamic in vivo 23Na fluxes in the brain of a preclinical rodent analogue of migraine. Ultra-high field 23Na magnetic resonance imaging (MRI) at 21.1 T has demonstrated potential to quantify sodium concentrations with good spatial and temporal resolution after the onset of central sensitization. Sprague-Dawley male rats with implanted intraperitoneal lines were studied by MRI before and after an in situ injection of 10 mg/kg of nitroglycerin (NTG) vs vehicle and saline controls. Slice-selective 23Na images were acquired using a multislice free induction decay–based chemical shift imaging sequence with resolution of 1.1 × 1.1 × 3 mm for a 9-minute acquisition. A total of 27 repeated scans were acquired over 1 hour of baseline scanning and longitudinally up to 3 hours after injection. Increases of 23Na MRI signal in the brainstem, extracerebral cerebrospinal fluid, and cisterna magna were evident almost immediately after NTG injection, gaining significance from controls in 36 minutes. The cerebellum and third ventricle also showed sustained trends of increased 23Na, with the former gaining significance at over 2 hours after NTG injection. The data provide evidence of an early change in sodium concentration, markedly in posterior fossa cerebrospinal fluid and brainstem regions. Further study of fluctuations of sodium concentration and their modulation with treatments could help understand the dynamic features of migraine, locate a putative migraine generator, and guide development of therapeutic measures to correct the disturbance of sodium homeostasis.

Longitudinal 23Na magnetic resonance imaging maps the evolution of acute migraine after nitroglycerine administration reporting significant, sustained increases in brainstem and cerebrospinal fluid sodium before established behavioral metrics.

aCenter for Interdisciplinary Magnetic Resonance, The National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States

bDepartment of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, United States

cMolecular Neurology Program, Huntington Medical Research Institutes, Pasadena, CA, United States

Corresponding author. Address: Chemical and Biomedical Engineering, FAMU-FSU College of Engineering and Center for Interdisciplinary Magnetic Resonance, National High Magnetic Field Laboratory, Florida State University, 1800 E Paul Dirac Drive, Tallahassee, FL 32310, United States. E-mail address: (S.C. Grant).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

M.G. Harrington and S.C. Grant are co-senior authors.

Received November 02, 2017

Received in revised form April 12, 2018

Accepted May 03, 2018

© 2018 International Association for the Study of Pain
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