Release of substance P, calcitonin gene-related peptide and prostaglandin E2 from rat dura mater encephali following electrical and chemical stimulation in vitro.
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.
Ebersberger
A
A
University of Jena, Department of Physiology I, Germany.
Averbeck
B
B
Messlinger
K
K
Reeh
P W
PW
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
D012701:Serotonin; D013373:Substance P; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D001920:Bradykinin