Dural Inflammation Model of Migraine Pain

Lee A. Phebus1, Kirk W. Johnson1

1 Eli Lilly and Company, Indianapolis, Indiana
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.1
DOI:  10.1002/0471142301.ns0901s06
Online Posting Date:  May, 2001
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The cause of migraine pain is controversial. One recently proposed theory is that migraine pain may originate from inflammation of the meninges, particularly the dural membranes that surround the brain. This theory proposes that, during a migraine, there is an idiopathic activation of trigeminal sensory afferents, resulting in nociceptive transmission to the CNS as well as the release of proÔÇÉinflammatory substances in the periphery, particularly the dura. Dural inflammation is thought to lower the nociceptive threshold of dural afferents and facilitate nociceptive transmission to the central nervous system. In the procedure described in this unit, trigeminal sensory afferents are activated by electrically stimulating the trigeminal ganglion. This stimulation causes trigeminal peripheral sensory afferents to depolarize, inflammatory substances to be released from these afferents, and dural inflammation to appear. Dural inflammation is quantified by measuring plasma protein extravasation. The basic protocol describes this model in rats, and the alternate protocol describes the analogous procedure in guinea pigs.

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Table of Contents

  • Basic Protocol 1: Assessment of Dural Extravasation in Rats as a Model of Migraine Pain
  • Alternate Protocol 1: Assessment of Dural Extravasation in Guinea Pigs
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
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Basic Protocol 1: Assessment of Dural Extravasation in Rats as a Model of Migraine Pain

  • Male Wistar rats, 250 to 350 g, group housed
  • 50 mg/ml sodium pentobarbital solution (for anesthesia)
  • 2% (w/v) chlorhexidine surgical scrub antiseptic solution (Fort Dodge Animal Health)
  • 50 mg/ml Evans Blue solution (see recipe; for injection)
  • Test compound in saline (0.9% NaCl) or other appropriate vehicle
  • 70% (v/v) glycerin in water
  • Electrodes (e.g., David Kopf model RNE 300×‐50 mm)
  • Two electrode manipulators for stereotaxic apparatus (e.g., David Kopf model 1460)
  • Electrode holders (e.g., David Kopf model 1770 or 1771)
  • Clamping device (e.g., David Kopf model 1772)
  • Constant‐current electrical tissue stimulator (Grass 888 or equivalent)
  • Electric hair clippers
  • Stereotaxic apparatus with rat adapter (e.g., David Kopf 1400 series)
  • Temperature controller with rectal temperature probe and small heating blanket (e.g., YSI model 73A controller with model 402 temperature probe, and a conventional electric heating pad)
  • Small hemostats
  • Cotton swabs
  • Fine‐tipped felt pen
  • Hand‐held electric drill (e.g., Dremel model 260)
  • Small ball‐type dental bur (e.g., SS White Burs, model HP1)
  • Fluorescence microscope with spectrophotometer (e.g., Carl Zeiss)
NOTE: For experiments involving oral administration of test compounds, animals should be fasted overnight before experimentation to enhance the speed of oral absorption.
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Literature Cited

Literature Cited
   Buzzi, M.G., Bonamini, M., and Moskowitz, M.A. 1995. Neurogenic model of migraine. Cephalalgia 15:277‐280.
   Johnson, K.W. and Phebus, L.A. 1998. A fluorescence‐based method for assessing dural protein extravasation induced by trigeminal ganglion stimulation. J. Neurosci. Methods 81:19‐24.
   Johnson, K.W., Schaus, J.M., Durkin, M.M., Audia, J.E., Kaldor, S.W., Flaugh, M.E., Adham, N., Zgombick, J.M., Cohen, M.L., Branchek, T.A., and Phebus, L.A. 1997. 5‐HT1F receptor agonists inhibit neurogenic dural inflammation in guinea pigs. Neuroreport 8:2237‐2240.
   Moskowitz, M.A. 1992. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci. 13:307‐311.
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