PAC1 receptor blockade reduces central nociceptive activity: new approach for primary headache?

Pain
Jan HoffmannPeter J Goadsby

Abstract

Pituitary adenylate cyclase activating polypeptide-38 (PACAP38) may play an important role in primary headaches. Preclinical evidence suggests that PACAP38 modulates trigeminal nociceptive activity mainly through PAC1 receptors while clinical studies report that plasma concentrations of PACAP38 are elevated in spontaneous attacks of cluster headache and migraine and normalize after treatment with sumatriptan. Intravenous infusion of PACAP38 induces migraine-like attacks in migraineurs and cluster-like attacks in cluster headache patients. A rodent-specific PAC1 receptor antibody Ab181 was developed, and its effect on nociceptive neuronal activity in the trigeminocervical complex was investigated in vivo in an electrophysiological model relevant to primary headaches. Ab181 is potent and selective at the rat PAC1 receptor and provides near-maximum target coverage at 10 mg/kg for more than 48 hours. Without affecting spontaneous neuronal activity, Ab181 effectively inhibits stimulus-evoked activity in the trigeminocervical complex. Immunohistochemical analysis revealed its binding in the trigeminal ganglion and sphenopalatine ganglion but not within the central nervous system suggesting a peripheral site of action. The pharmacolog...Continue Reading

References

Oct 16, 1989·Biochemical and Biophysical Research Communications·A MiyataD H Coy
Mar 11, 1985·Brain Research·P J Goadsby, G J MacDonald
May 8, 2002·Cephalalgia : an International Journal of Headache·L H LassenJ Olesen
Mar 12, 2004·The New England Journal of Medicine·Jes OlesenUNKNOWN BIBN 4096 BS Clinical Proof of Concept Study Group
Jul 9, 2004·British Journal of Pharmacology·Robin James StorerPeter J Goadsby
Sep 29, 2006·The European Journal of Neuroscience·A BergerotP J Goadsby
Feb 8, 2008·Cephalalgia : an International Journal of Headache·A RahmannM Ashina
Dec 5, 2008·Brain : a Journal of Neurology·Henrik Winther SchytzMessoud Ashina
Dec 27, 2008·Pharmacology & Therapeutics·Louise Dickson, Keith Finlayson
Feb 18, 2009·Cephalalgia : an International Journal of Headache·L J BoniS Gupta
Oct 27, 2010·Cephalalgia : an International Journal of Headache·Kayi Y ChanSaurabh Gupta
Oct 27, 2010·Cephalalgia : an International Journal of Headache·Andrew P HoTony W Ho
Dec 22, 2010·Cephalalgia : an International Journal of Headache·Hans-Christoph DienerJana Podhorna
Mar 9, 2011·Cephalalgia : an International Journal of Headache·David J HewittTony W Ho
Sep 29, 2011·British Journal of Pharmacology·Alain Couvineau, Marc Laburthe
Apr 20, 2013·Cephalalgia : an International Journal of Headache·Bernadett TukaJános Tajti
Aug 24, 2013·Cephalalgia : an International Journal of Headache·Ronald MarcusTanya Z Fischer
Jan 13, 2015·Annals of Clinical and Translational Neurology·Alessandro S ZagamiPeter J Goadsby
Jun 9, 2016·Cephalalgia : an International Journal of Headache·Tiffini VossDavid Michelson
Aug 1, 2016·The Journal of Headache and Pain·Bernadett TukaJános Tajti
Feb 10, 2017·Physiological Reviews·Peter J GoadsbySimon Akerman
Nov 25, 2017·The New England Journal of Medicine·Stephen D SilbersteinErnesto Aycardi
Nov 25, 2017·The New England Journal of Medicine·Peter J GoadsbyRobert A Lenz
Nov 28, 2017·Lancet Neurology·Jan Hoffmann, Arne May
Jul 11, 2019·The New England Journal of Medicine·Peter J GoadsbyJames M Martinez

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Citations

Jun 12, 2020·The Journal of Headache and Pain·David B ClemowAndrew M Blumenfeld
Aug 28, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Luca GianiMassimo Leone
Nov 24, 2020·Der Schmerz·Andreas Straube, Stefanie Förderreuther
Feb 12, 2021·Cephalalgia : an International Journal of Headache·Nita Katarina Frifelt WienholtzMessoud Ashina
Apr 13, 2021·Current Opinion in Neurology·David Moreno-AjonaPeter J Goadsby
May 19, 2021·Neurology India·David Moreno-AjonaPeter James Goadsby
Sep 19, 2021·Expert Opinion on Drug Metabolism & Toxicology·Abimael González-HernándezCarlos M Villalón

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