title: Characterization of a mouse model of headache.
abstract: Migraine and other primary headache disorders affect a large population and cause debilitating pain. Establishing animal models that display behavioral correlates of long-lasting and ongoing headache, the most common and disabling symptom of migraine, is vital for the elucidation of disease mechanisms and identification of drug targets. We have developed a mouse model of headache, using dural application of capsaicin along with a mixture of inflammatory mediators (IScap) to simulate the induction of a headache episode. This elicited intermittent head-directed wiping and scratching as well as the phosphorylation of c-Jun N-terminal kinase in trigeminal ganglion neurons. Interestingly, dural application of IScap preferentially induced FOS protein expression in the excitatory but not inhibitory cervical/medullary dorsal horn neurons. The duration of IScap-induced behavior and the number of FOS-positive neurons correlated positively in individual mice; both were reduced to the control level by the pretreatment of antimigraine drug sumatriptan. Dural application of CGRP(8-37), the calcitonin gene-related peptide (CGRP) receptor antagonist, also effectively blocked IScap-induced behavior, which suggests that the release of endogenous CGRP in the dura is necessary for IScap-induced nociception. These data suggest that dural IScap-induced nocifensive behavior in mice may be mechanistically related to the ongoing headache in humans. In addition, dural application of IScap increased resting time in female mice. Taken together, we present the first detailed study using dural application of IScap in mice. This headache model can be applied to genetically modified mice to facilitate research on the mechanisms and therapeutic targets for migraine headache.
authors.affiliation: Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Dongyue
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Chang-Shen
authors.initials: CS
authors.lastname: Qiu
authors.affiliation: Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Peterson
authors.affiliation: Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yuchio
authors.initials: Y
authors.lastname: Yanagawa
authors.affiliation: Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Cao
mesh_terms: D000818:Animals; D002211:Capsaicin; D004195:Disease Models, Animal; D004388:Dura Mater / Q000378:metabolism; D005260:Female; D006261:Headache / Q000139:chemically induced / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D012668:Trigeminal Ganglion / Q000378:metabolism*
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D002211:Capsaicin