title: Sodium MRI in a rat migraine model and a NEURON simulation study support a role for sodium in migraine.
abstract: BACKGROUND
  Increased lumbar cerebrospinal fluid (CSF) sodium has been reported during migraine. We used ultra-high field MRI to investigate cranial sodium in a rat migraine model, and simulated the effects of extracellular sodium on neuronal excitability.
  
  
  METHODS
  Behavioral changes in the nitroglycerin (NTG) rat migraine model were determined from von Frey hair withdrawal response and photography. Central sensitization was measured by counting cFos-immunoreactive cells in the trigeminal nucleus caudalis (TNC). Sodium was quantified in vivo by ultra-high field sodium MRI at 21 Tesla. Effects of extracellular sodium on neuronal excitability were modeled using NEURON software.
  
  
  RESULTS
  NTG decreased von Frey withdrawal threshold (p=0.0003), decreased eyelid vertical height:width ratio (p<0.0001), increased TNC cFos stain (p<0.0001), and increased sodium between 7.5 and 17% in brain, intracranial CSF, and vitreous humor (p<0.05). Simulated neurons exposed to higher sodium have more frequent and earlier spontaneous action potentials, and corresponding earlier sodium and potassium currents.
  
  
  CONCLUSIONS
  In the rat migraine model, sodium rises to levels that increase neuronal excitability. We propose that rising sodium in CSF surrounding trigeminal nociceptors increases their excitability and causes pain and that rising sodium in vitreous humor increases retinal neuronal excitability and causes photosensitivity.
authors.affiliation: Molecular Neurology Program, Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, CA 91101, USA. mghworks@hmri.org
authors.forename: Michael G
authors.initials: MG
authors.lastname: Harrington
authors.forename: Eduard Y
authors.initials: EY
authors.lastname: Chekmenev
authors.forename: Victor
authors.initials: V
authors.lastname: Schepkin
authors.forename: Alfred N
authors.initials: AN
authors.lastname: Fonteh
authors.forename: Xianghong
authors.initials: X
authors.lastname: Arakaki
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003198:Computer Simulation; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging; D008881:Migraine Disorders / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D012964:Sodium / Q000378:metabolism*
chemical_list: D012964:Sodium