Article (Scientific journals)
The nonpeptide calcitonin gene-related peptide receptor antagonist BIBN4096BS lowers the activity of neurons with meningeal input in the rat spinal trigeminal nucleus
Fischer, Michael Jochen Marco; Koulchitsky, Stanislav; Messlinger, Karl
2005In Journal of Neuroscience, 25 (25), p. 5877-5883
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Keywords :
migraine; nociception; CGRP; trigeminal; electrophysiology; brainstem; headache; BIBN4096BS
Abstract :
[en] Calcitonin gene-related peptide (CGRP) has been suggested to play a major role in the pathogenesis of migraines and other primary headaches. CGRP may be involved in the control of neuronal activity in the spinal trigeminal nucleus (STN), which integrates nociceptive afferent inputs from trigeminal tissues, including intracranial afferents. The activity of STN neurons is thought to reflect the activity of central trigeminal nociceptive pathways causing facial pain and headaches in humans. In a rat model of meningeal nociception, single neuronal activity in the STN was recorded. All units had receptive fields located in the exposed parietal dura mater. Heat and cold stimuli were repetitively applied to the dura in a fixed pattern of ramps and steps. The nonpeptide CGRP receptor antagonist BIBN4096BS was topically applied onto the exposed dura or infused intravenously. BIBN4096BS (300 microg/kg, i.v.) reduced spontaneous activity by approximately 30%, the additional dose of 900 microg/kg intravenously by approximately 50% of the initial activity, whereas saline had no effect. The activity evoked by heat ramps was also reduced after BIBN4096BS (900 microg/kg, i.v.) by approximately 50%. Topical administration of BIBN4096BS (1 mm) did not significantly change the spontaneous neuronal activity within 15 min. We conclude that the endogenous release of CGRP significantly contributes to the maintenance of spontaneous activity in STN neurons. Blockade of CGRP receptors, possibly at central and peripheral sites, may therefore be an effective way to decrease nociceptive transmission. This may offer a new therapeutic strategy for the treatment of facial pain and primary headaches
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Fischer, Michael Jochen Marco
Koulchitsky, Stanislav ;  Université de Liège > Département des sciences biomédicales et précliniques > Pharmacologie
Messlinger, Karl
Language :
English
Title :
The nonpeptide calcitonin gene-related peptide receptor antagonist BIBN4096BS lowers the activity of neurons with meningeal input in the rat spinal trigeminal nucleus
Publication date :
2005
Journal title :
Journal of Neuroscience
ISSN :
0270-6474
eISSN :
1529-2401
Publisher :
Soc Neuroscience
Volume :
25
Issue :
25
Pages :
5877-5883
Peer reviewed :
Peer Reviewed verified by ORBi
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since 02 August 2017

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