Role of Pituitary Adenylate Cyclase Activating Polypeptide in the nitroglycerin-induced migraine model of the mouse
Adrienn
Markovics1*,
Katalin
Sándor1,
Eva
Szoke1,
Viktoria
Kormos1,
Balázs
Gaszner2,
Dóra
Reglodi2,
Akemichi
Baba3,
Janos
Tajti4,
László
Vécsei4,
Bernadett
Tuka4,
Arpad
Parducz4,
Annamaria
Fejes4,
Zsuzsanna
Bahár4,
János
Szolcsányi1 and
Zsuzsanna
Helyes1
-
1
University of Pecs, Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Hungary
-
2
University of Pecs, Department of Anatomy, Faculty of Medicine, Hungary
-
3
Osaka University, Graduate School of Pharmaceutical Sciences, Japan
-
4
University of Szeged, Neurology Department Faculty of Medicine , Hungary
Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the VIP/glucagon/secretin family, it exerts multiple actions via three G-protein-coupled receptors. They activate signaling cascades such as adenylate cyclase, phospholipase C, mitogen-activated protein kinases which induces Ca2+ mobilization. Migraine is a neurovascular disorder characterized by severe unilateral head pain and associated symptoms, such as photophobia. We have recently proved the excitatory function of PACAP in the central nervous system in a variety of pain models.
Therefore, the aim of the present study was to investigate the role of PACAP in nitroglycerin(NG)-induced light aversion behaviour and c-Fos immunoreactivity in the trigeminal nucleus using PACAP gene-deleted (PACAP-/-) mice and their wildtype (PACAP+/+) counterparts.
Migraine-like pathophysiological alterations were induced by ip. injection of 10 mg/kg nitroglycerin as described in the literature. The mice were individually observed in a custom made light-dark box (40cmx20cm) for 2 hours and the time spent in the light side were analyzed in each 300 s interval. At the end of the experiment, the animals were sacrifized and perfused with 4 % paraformaldehyde. C-Fos positivity was determined in the medullar trigeminal nucleus with immunohistochemistry and quantitative analysis was performed.
Our results showed significantly reduced light aversive behaviour in PACAP-/- mice both in the early phase (0-30 min) due to the acute vasodilating effect of NG and in the late phase (90-120 min) when sensitization of the trigeminal system is supposed to be involved. Furthermore, the number of c-Fos immunopositive neurons was also significantly smaller in the trigeminal nucleus of the knockouts 2 h after NG injection.
These data suggest a pro-nociceptive role of PACAP in the trigeminal system involved in migaine-like pain. Identification of its targets might open interesting future perspectives in novel anti-migraine therapy.
Conference:
IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010.
Presentation Type:
Poster Presentation
Topic:
Sensory and motor systems
Citation:
Markovics
A,
Sándor
K,
Szoke
E,
Kormos
V,
Gaszner
B,
Reglodi
D,
Baba
A,
Tajti
J,
Vécsei
L,
Tuka
B,
Parducz
A,
Fejes
A,
Bahár
Z,
Szolcsányi
J and
Helyes
Z
(2010). Role of Pituitary Adenylate Cyclase Activating Polypeptide in the nitroglycerin-induced migraine model of the mouse.
Front. Neurosci.
Conference Abstract:
IBRO International Workshop 2010.
doi: 10.3389/conf.fnins.2010.10.00244
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Received:
05 May 2010;
Published Online:
05 May 2010.
*
Correspondence:
Adrienn Markovics, University of Pecs, Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Pecs, Hungary, adri.markovics@yahoo.de