Periaqueductal gray calcitonin gene-related peptide modulates trigeminovascular neurons

Cephalalgia : an International Journal of Headache
P Pozo-RosichP J Goadsby

Abstract

Calcitonin gene-related peptide (CGRP) receptor antagonism is an approach to migraine therapy. The locus of action of antimigraine treatment is not resolved. The objective was to investigate CGRP receptors in the ventrolateral periaqueductal gray (vlPAG) involved in the modulation of trigeminovascular nociception by descending influences on neurotransmission. The presence of calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1), which form functional CGRP receptors, was investigated. CGRP and its receptor antagonists, olcegepant and CGRP (8-37), were microinjected into the vlPAG while changes of neural responses in the trigeminocervical complex (TCC) were monitored. Immunoreactivity indicated the presence of functional CGRP receptor components in the vlPAG and adjacent mesencephalic trigeminal nucleus. Inhibition of TCC responses to stimulation of dural afferents and ophthalmic cutaneous receptive fields after microinjection of bicuculline into vlPAG indicated a connection between the vlPAG and TCC neurons. CGRP facilitated these TCC responses, whereas olcegepant and CGRP (8-37) decreased them. CGRP and its receptor antagonists act on neurons in the region of vlPAG to influence nociceptive tr...Continue Reading

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Citations

Jun 3, 2015·British Journal of Clinical Pharmacology·Andrew F Russo
Mar 24, 2018·Cephalalgia : an International Journal of Headache·Erica R HendrikseChristopher S Walker
Apr 5, 2018·Cephalalgia : an International Journal of Headache·Roberta Messina, Peter J Goadsby
Jul 4, 2018·Cephalalgia : an International Journal of Headache·Marta Vila-PueyoSimon Akerman
Feb 8, 2018·Cephalalgia : an International Journal of Headache·Philip Robert HollandMarta Vila-Pueyo
Apr 16, 2019·Headache·Smriti IyengarSheena K Aurora
Apr 21, 2019·Journal of Neurology, Neurosurgery, and Psychiatry·Peter J GoadsbySheena K Aurora
Apr 7, 2020·Current Opinion in Neurology·David Moreno-AjonaPeter J Goadsby
Feb 10, 2017·Physiological Reviews·Peter J GoadsbySimon Akerman
Aug 30, 2019·The Journal of Headache and Pain·Andrea M HarriottPhilip R Holland
Feb 1, 2020·Cephalalgia : an International Journal of Headache·Philip R HollandMarta Vila-Pueyo
Mar 23, 2017·Journal of Neurology·Francesca PuleddaPeter J Goadsby
Nov 19, 2018·Nature Reviews. Neurology·Nazia Karsan, Peter J Goadsby
Mar 21, 2018·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Philip R Holland, Peter J Goadsby
Sep 23, 2020·Annals of Neurology·Håkan AshinaHenrik W Schytz

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