title: Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro.
abstract: Neurogenic inflammation of the dura, expressed in plasma extravasation and vasodilatation, putatively contributes to different types of headache. A novel in vitro preparation of the fluid-filled skull cavities was developed to measure mediator release from dura mater encephali upon antidromic electrical stimulation of the trigeminal ganglion and after application of a mixture of inflammatory mediators (serotonin, histamine and bradykinin, 10(-5) M each, pH 6.1) to the arachnoid side of rat dura. The release of calcitonin gene-related peptide, substance P and prostaglandin E2 from dura mater was measured in 5-min samples of superfusates using enzyme immunoassays. Orthodromic chemical and antidromic electrical stimulation of dural afferents caused significant release of calcitonin gene-related peptide (2.8- and 4.5-fold of baseline). The neuropeptide was found to be increased during the 5-min stimulation period and returned to baseline (20.9 +/- 12 pg/ml) in the sampling period after stimulation. In contrast, release of substance P remained at baseline levels (19.3 +/- 11 pg/ml) throughout the experiment. Prostaglandin E2 release was elevated during chemical and significantly also after antidromic electrical stimulation (6- and 4.2-fold of baseline, which was 305 +/- 250 pg/ml). Prostaglandin E2 release outlasted the stimulation period for at least another 5 min. The data support the hypothesis of neurogenic inflammation being involved in headaches and provide new evidence for prostaglandin E2 possibly facilitating meningeal nociceptor excitation and, hence, pain.
authors: University of Jena, Department of Physiology I, Germany.
authors: A
authors: A
authors: Ebersberger
authors: B
authors: B
authors: Averbeck
authors: K
authors: K
authors: Messlinger
authors: P W
authors: PW
authors: Reeh
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001099:Arachnoid / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D006261:Headache / Q000503:physiopathology*; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology; D009475:Neurons, Afferent / Q000378:metabolism; D009619:Nociceptors / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D012701:Serotonin; D013373:Substance P; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D001920:Bradykinin