Headache Group

Headache is the one of the most frequent neurological disorder. We are investigating pathophysiological mechanisms related to the development of migraine and chronic headaches in experimental animals and in vitro. In the past, we have studied as to whether NO can activate the trigeminal nerve system (Offenhauser et al.,20045) and changes within meninges after nitric oxide donor infusion (Reuter et al., 2002).

With respect to cluster headache, we have focussed on the role of oxygen on neuropeptide release (CGRP) and neurogenic inflammation. In line, we were able to demonstrate that selective COX-2 inhibitors attenuate plasma protein extravasation and reduce the activation of trigeminal brain stem neurons after unilateral trigeminal ganglion stimulation (Schuh-Hofer et al., 2005).

Our current focus is the role of nitric oxide in the pathopyhsiology of acute and chronic headaches. We have established a chronic headache model in which the meninges can be stimulated repeatedly. By doing so, we generate meningeal inflammation and can assess changes within primary and secondary trigeminal neurons after repetitive stimulation. In particular, we are interested on the role of nitric oxide in the development of chronic headaches.

Our second focus is a trigeminal ganglia cell culture modell. We intend to use this model to study properties of primary trigeminal neurons. So far, we have determined that trigeminal neurons are capable to express COX-2 in a functionally significant mode. The trigeminal neuronal culture will be used to study the interaction of NO and COX-2 related to migraine pathopyhsiology and the change of properties of these neurons in a sensitized state. In order to assess these questions we use immunohistological, biochemical and molecular biological techniques. Finally, and in a novel approach we are trying to establish a behavioural modell to assess headaches in experimental animals following meningeal stimulation.

Selected references

L. Neeb and U Reuter
NO and NFkB in migraine. Curr Drug Targets. 2005; in press

S. Schuh-Hofer, M. Tayefeh, U. Reuter, U. Dirnagl and, G. Arnold.
Effects of Parecoxib on Plasma Protein Extravasation and c-Fos Expression in the Rat" Headache 2005, in press

N Offenhauser, T Zinck, J Hoffmann, K Schiemann, S Schuh-Hofer, W. Rohde, G Arnold, U Dirnagl, I Jansen-Olesen and U Reuter
CGRP release and c-fos expression within trigeminal nucleus caudalis of the rat following glyceryltrinitrate infusion. Cephalagia 2005 Mar;25(3):225-36.

U Reuter and A May
Voraussetzungen für das Symptom Kopfschmerz- Aspekte zur Pathogenese. Schmerz. 2004 Oct;18(5):357-62.

Sanchez-del-Rio M and U Reuter
Migraine aura: new information on anderlying mechanisms. Curr Opin Neurol. 2004 Jun;17(3):289-293.

Reuter U, Salomone S, Ickenstein GW, C Waeber
Effects of chronic sumatriptan and zolmitriptan treatment on 5-HT 1 receptor expression and function in rats. Cephalalgia. 2004 May, 24(5):398-407.

Schuh-Hofer S, Boehnke C; Reuter U; Siekmann W; Lindauer U; Arnold G; U Dirnagl.
A fluorescence based method to assess plasma protein extravasation in rat dura mater using confocal laser scanning microscopy. Brain Res Brain Res Protoc. 2003 Oct 12 (2): 77-82.

Reuter U, Sanchez Del Rio M, Carpay J, Boes C, S Silberstein
Placebo adverse events in headache trials: headache as an adverse event of placebo. Cephalalgia. 2003 Sep; 23(7):496-503.

Sanchez del Rio M and U Reuter
Pathophysiology of Headache. Curr Neurol Neurosci Rep. 2003; 3(2):109-114.

Reuter U, Chiarugi A, Bolay H, MA Moskowitz
Nuclear factor-kappaB as a molecular target for migraine therapy. Ann Neurol. 2002 Apr; 51(4):507-16.

Reuter U*, Bolay H*, Dunn A*, Huang Z, Boas D, MA Moskowitz
Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med. 2002 Feb; 8(2):136-42. * gleichberechtigte Erstautoren

Reuter U, Bolay H, Jansen-Olesen I, Chiarugi A, del Rio MS, Letourneau R, Theoharides TC, Waeber C, MA Moskowitz .
Delayed inflammation in rat meninges: implications for migraine pathophysiology. Brain. 2001 Dec; 124(Pt 12):2490-2502.

Team Reuter

Project Leader:
Uwe Reuter

Staff:
Lars Neeb
Jan Hoffmann
Sonja Blumenau
Anna Hegele

Graduate Student:
Martina Scheinhof