title: A novel method for modeling facial allodynia associated with migraine in awake and freely moving rats.
abstract: Migraine is a neurovascular disorder that induces debilitating headaches associated with multiple symptoms including facial allodynia, characterized by heightened responsivity to normally innocuous mechanical stimuli. It is now well accepted that immune activation and immune-derived inflammatory mediators enhance pain responsivity, including the trigeminal system. Nociceptive ("pain" responsive) trigeminal nerves densely innervate the cranial meninges. We have recently proposed that the meninges may serve as a previously unidentified, key interface between the peripheral immune system and the CNS with potential implications for understanding underlying migraine mechanisms. Our focus here is the development of a model for facial allodynia associated with migraine. We developed a model wherein an indwelling catheter is placed between the skull and dura, allowing immunogenic stimuli to be administered over the dura in awake and freely moving rats. Since the catheter does not contact the brain itself, any proinflammatory cytokines induced following manipulation derive from resident or recruited meningeal immune cells. While surgery alone does not alter immune activation markers, TNF or IL6 mRNA and/or protein, it does decrease gene expression and increase protein expression of IL-1 at 4 days after surgery. Using this model we show the induction of facial allodynia in response to supradural administration of either the HIV glycoprotein gp120 or inflammatory soup (bradykinin, histamine, serotonin, and prostaglandin E2), and the induction of hindpaw allodynia in our model after inflammatory soup. This model allows time- and dose-dependent assessment of the relationship between changes in meningeal inflammation and corresponding exaggerated pain behaviors.
authors.affiliation: Department of Psychology & Center for Neurosciences, University of Colorado at Boulder, Boulder, CO 80309-0345, USA. wieseler@colorado.edu
authors.forename: Julie
authors.initials: J
authors.lastname: Wieseler
authors.forename: Amanda
authors.initials: A
authors.lastname: Ellis
authors.forename: David
authors.initials: D
authors.lastname: Sprunger
authors.forename: Kim
authors.initials: K
authors.lastname: Brown
authors.forename: Andrew
authors.initials: A
authors.lastname: McFadden
authors.forename: John
authors.initials: J
authors.lastname: Mahoney
authors.forename: Niloofar
authors.initials: N
authors.lastname: Rezvani
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000503:physiopathology; D001920:Bradykinin / Q000009:adverse effects; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002408:Catheters, Indwelling; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005145:Face / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000009:adverse effects; D006632:Histamine / Q000009:adverse effects; D006930:Hyperalgesia / Q000209:etiology; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000009:adverse effects; D013997:Time Factors; D014851:Wakefulness; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001920:Bradykinin; D039481:CD11b Antigen; D016207:Cytokines; D004338:Drug Combinations; D015699:HIV Envelope Protein gp120; D006632:Histamine; D012701:Serotonin; C067980:CD68 antigen, human; D000097382:CD68 Molecule