Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus

Journal article


Publication Details

Author(s): Fischer M, Schmidt J, Koulchitsky S, Klussmann S, Vater A, Meßlinger K
Journal: Journal of Headache and Pain
Publication year: 2018
Volume: 19
Journal issue: 1
ISSN: 1129-2369
eISSN: 1129-2377


Abstract

BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been demonstrated to be therapeutically effective in migraine. In parallel, CGRP receptor inhibition has been shown to lower spinal trigeminal neuron activity in animal models of meningeal nociception.
METHODS: In a rat model of meningeal nociception, single cell activity of neurons in the spinal trigeminal nucleus with meningeal afferent input was recorded to test a further pharmacological approach, scavenging CGRP with a CGRP-binding L-RNA oligonucleotide, the L-aptamer NOX-C89. Cumulative ascending doses of NOX-C89 were intravenously infused.
RESULTS: Spontaneous activity of spinal trigeminal neurons did not change after 0.05 mg/kg NOX-C89, however, after additional infusion of 0.5 mg/kg and 5 mg/kg NOX-C89, spontaneous activity was dose-dependently reduced. Identical doses of a control L-aptamer had no effect. This pharmacological effect of NOX-C89 was observed 10-25 min after infusion, but no difference was detected in the period 0-5 min. For comparison, the previously investigated CGRP receptor antagonist olcegepant had reduced activity within 5 min after infusion. Alongside the reduced spontaneous activity, after infusion of NOX-C89 the heat-induced neuronal activity was abolished.
CONCLUSIONS: Scavenging CGRP by mirror-image RNA aptamers provides further evidence that this approach can be used to control spinal trigeminal activity.


FAU Authors / FAU Editors

Fischer, Michael Prof. Dr.
Medizinische Fakultät
Meßlinger, Karl Prof. Dr.
Professur für Physiologie


External institutions with authors

Aptarion Biotech


How to cite

APA:
Fischer, M., Schmidt, J., Koulchitsky, S., Klussmann, S., Vater, A., & Meßlinger, K. (2018). Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus. Journal of Headache and Pain, 19(1). https://dx.doi.org/10.1186/s10194-018-0832-8

MLA:
Fischer, Michael, et al. "Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus." Journal of Headache and Pain 19.1 (2018).

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Last updated on 2019-01-03 at 19:08