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Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus.
J Headache Pain 2018; 19(1):3JH

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.

Authors+Show Affiliations

Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, D-91054, Erlangen, Germany. Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, D-91054, Erlangen, Germany.Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, D-91054, Erlangen, Germany. Department of Pharmacology, University of Liège, Liège, Belgium.Aptarion Biotech, Berlin, Germany.Aptarion Biotech, Berlin, Germany.Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätstrasse 17, D-91054, Erlangen, Germany. karl.messlinger@fau.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29335794

Citation

Fischer, Michael J M., et al. "Effect of a Calcitonin Gene-related Peptide-binding L-RNA Aptamer On Neuronal Activity in the Rat Spinal Trigeminal Nucleus." The Journal of Headache and Pain, vol. 19, no. 1, 2018, p. 3.
Fischer MJM, Schmidt J, Koulchitsky S, et al. Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus. J Headache Pain. 2018;19(1):3.
Fischer, M. J. 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. The Journal of Headache and Pain, 19(1), p. 3. doi:10.1186/s10194-018-0832-8.
Fischer MJM, et al. Effect of a Calcitonin Gene-related Peptide-binding L-RNA Aptamer On Neuronal Activity in the Rat Spinal Trigeminal Nucleus. J Headache Pain. 2018 Jan 15;19(1):3. PubMed PMID: 29335794.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal activity in the rat spinal trigeminal nucleus. AU - Fischer,Michael J M, AU - Schmidt,Jakob, AU - Koulchitsky,Stanislav, AU - Klussmann,Sven, AU - Vater,Axel, AU - Messlinger,Karl, Y1 - 2018/01/15/ PY - 2017/10/06/received PY - 2017/12/29/accepted PY - 2018/1/17/entrez PY - 2018/1/18/pubmed PY - 2018/6/27/medline KW - Headache KW - Meningeal nociception KW - Migraine SP - 3 EP - 3 JF - The journal of headache and pain JO - J Headache Pain VL - 19 IS - 1 N2 - 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. SN - 1129-2377 UR - https://www.unboundmedicine.com/medline/citation/29335794/Effect_of_a_calcitonin_gene_related_peptide_binding_L_RNA_aptamer_on_neuronal_activity_in_the_rat_spinal_trigeminal_nucleus_ L2 - https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0832-8 DB - PRIME DP - Unbound Medicine ER -