title: Biphasic response to nitric oxide of spinal trigeminal neurons with meningeal input in rat--possible implications for the pathophysiology of headaches.
abstract: Nitric oxide (NO) is suggested to play a causative role in the pathogenesis of primary headaches. Infusion of NO donors can trigger headache attacks, and products of NO metabolism are found to be increased in the cranial circulation in patients suffering from such headaches. To examine if NO is involved in mediating and maintaining spinal trigeminal neuronal activity, an animal model of meningeal nociception was used. In barbiturate-anesthetized rats, a cranial window was made to expose the parietal dura mater. An access to the medullary brain stem allowed extracellular action potentials to be recorded from neurons in the spinal trigeminal nucleus that received afferent input from the exposed dura. Slow intravenous infusion of the NO donor, sodium nitroprusside (SNP, 50 microg/kg), transiently increased spontaneous activity in a subset of neurons and, with a latency of 50 min, caused a progressive increase in impulse activity across the entire sample of neurons. A similar pattern of delayed activation was seen after topical application of the same dose of SNP onto the exposed medulla. Slow injection of the nonspecific inhibitor of NO synthase, N(omega)-nitro-l-arginine methyl ester (20 mg/kg), reduced the spontaneous activity in all neurons within 15 min. The results suggest that NO can induce delayed, slowly developing activation of central trigeminal neurons and that endogenous release of NO may contribute to the ongoing activity of these neurons. The delayed changes in neuronal activity may include gene expression of pro-nociceptive mediators. These mechanisms may be relevant for the pathogenesis of chronic headaches.
authors.affiliation: Institute of Physiology and Experimental Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, D-91054 Erlangen, Germany.
authors.forename: Stansilav
authors.initials: S
authors.lastname: Koulchitsky
authors.forename: Michael J M
authors.initials: MJ
authors.lastname: Fischer
authors.forename: Roberto
authors.initials: R
authors.lastname: De Col
authors.forename: Philipp M
authors.initials: PM
authors.lastname: Schlechtweg
authors.forename: Karl
authors.initials: K
authors.lastname: Messlinger
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D006261:Headache / Q000503:physiopathology*; D008297:Male; D008578:Meninges / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester