title: Sensitization of meningeal nociceptors: inhibition by naproxen.
abstract: Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of Adelta- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of Adelta- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA. dlevy1@bidmc.harvard.edu
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
authors.forename: Xi-Chun
authors.initials: XC
authors.lastname: Zhang
authors.forename: Moshe
authors.initials: M
authors.lastname: Jakubowski
authors.forename: Rami
authors.initials: R
authors.lastname: Burstein
mesh_terms: D000287:Administration, Topical; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004594:Electrophysiology; D007262:Infusions, Intravenous; D008297:Male; D008578:Meninges / Q000187:drug effects*; D009288:Naproxen / Q000008:administration & dosage*; D009578:Nitrobenzenes / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009288:Naproxen