title: Effects of CGRP receptor antagonism in nitroglycerin-induced hyperalgesia.
abstract: BACKGROUND
  The release of calcitonin gene-related peptide (CGRP) from trigeminal nerves plays a central role in the pathophysiology of migraine and clinical evidence shows an antimigraine effect for CGRP receptor antagonists. Systemic administration of nitroglycerin (NTG), a nitrovasodilator, consistently provokes spontaneous-like migraine attacks in migraine sufferers; in the rat, systemic NTG induces a condition of hyperalgesia, probably through the activation of cerebral/spinal structures involved in nociceptive transmission.
  
  
  OBJECTIVE
  The aim of this article is to test the analgesic effect of the CGRP receptor antagonist MK-8825 in two animal models of pain that may be relevant for migraine: the tail flick test and the formalin test performed during NTG-induced hyperalgesia.
  
  
  RESULTS
  MK-8825 showed analgesic activity when administered alone at both the tail flick test and the formalin test. Furthermore, the CGRP antagonist proved effective in counteracting NTG-induced hyperalgesia in both tests. MK-8825 indeed reduced the nociceptive behavior when administered either simultaneously or prior to (30-60 minutes before) NTG.
  
  
  CONCLUSIONS
  These data suggest that MK-8825 may represent a potential therapeutic tool for the treatment of migraine.
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Italy rosaria.greco@mondino.it.
authors.forename: R
authors.initials: R
authors.lastname: Greco
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Italy.
authors.forename: A S
authors.initials: AS
authors.lastname: Mangione
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino" National Neurological Institute, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Siani
authors.affiliation: Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, "C. Mondino" National Neurological Institute, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Blandini
authors.affiliation: Department of Internal Medicine and Therapeutics, Pharmacology and Toxicology Unit, University of Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vairetti
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Nappi
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Italy IRCCS Santa Lucia Foundation, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sandrini
authors.affiliation: Department of Brain and Behaviour, University of Pavia, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Buzzi
authors.affiliation: Laboratory of Neurophysiology of Integrative Autonomic Systems, Headache Science Centre, "C. Mondino" National Neurological Institute, Italy IRCCS Santa Lucia Foundation, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Tassorelli
mesh_terms: D000818:Animals; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D008881:Migraine Disorders / Q000503:physiopathology*; D005996:Nitroglycerin / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; C575097:MK-8825; D011725:Pyridines; D013141:Spiro Compounds; D005996:Nitroglycerin
keywords: CGRP receptor antagonist; Nitroglycerin; hyperalgesia; migraine