title: Sensitization of central trigeminovascular neurons: blockade by intravenous naproxen infusion.
abstract: We have previously observed that migraine attacks impervious to triptan therapy were readily terminated by subsequent i.v. administration of the non-steroidal anti-inflammatory drug (NSAID) ketorolac. Since such attacks were associated with periorbital allodynia--a symptom of central sensitization--we examined whether infusion of the NSAID naproxen can block sensitization of central trigeminovascular neurons in the medullary dorsal horn, using in vivo single-unit recording in the rat. Topical exposure of the cerebral dura to inflammatory soup (IS) for 5 min resulted in a short-term burst of activity (<8 min) and a long-lasting (>120 min) neuronal hyper-responsiveness to stimulation of the dura and periorbital skin (group 1). Infusion of naproxen (1 mg/kg) 2 h after IS (group 1) brought all measures of neuronal responsiveness back to the baseline values recorded prior to IS, and depressed ongoing spontaneous activity well below baseline. When given preemptively 1 h before IS (group 2), naproxen blocked the short-term burst of activity and every long-term measure of neuronal hyper-responsiveness that was studied in the central neurons. The same preemptive treatment, however, failed to block IS-induced short-term bursts of activity in C-unit meningeal nociceptors (group 3). The results suggest that parenteral administration of naproxen, unlike triptan therapy, can exert direct inhibition over central trigeminovascular neurons in the dorsal horn. Though impractical as a routine migraine therapy, parenteral NSAID administration should be useful as a non-narcotic rescue therapy for migraine in the setting of the emergency department.
authors.affiliation: Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Room 830, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jakubowski
authors.forename: D
authors.initials: D
authors.lastname: Levy
authors.forename: V
authors.initials: V
authors.lastname: Kainz
authors.forename: X-C
authors.initials: XC
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Kosaras
authors.forename: R
authors.initials: R
authors.lastname: Burstein
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy / Q000473:pathology; D009288:Naproxen / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D020671:Posterior Horn Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000294:innervation; D013997:Time Factors; D014276:Trigeminal Nerve / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen