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Objective: Chronic cluster headache belongs to the most disabling vasomotor pain conditions. Treatment usually implies medical treatment and oxygen application in case of acute pain attacks. Among the known triggers for cluster periods are orbital exenteration, head injury, dental extraction, impacted[for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Objective: Cluster Headache belongs to the most disabling vasomotor pain conditions. Treatment usually implies medical treatment and oxygen application in case of acute pain attacks. Even with maximal therapy patients often remain physically and mentally handicapped, sometimes even unable to work. [for full text, please go to the a.m. URL], 60. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit den Benelux-Ländern und Bulgarien

Capsaicin, the active substance in chilli peppers, activates the vanilloid type 1 receptor (VR1) rather than the vanilloid-like receptor (VRL1) in the trigeminal ganglion and nucleus of small and medium C- and Adelta-fibres. Capsaicin induces calcitonin gene-related peptide (CGRP) release when VR1 receptors are activated, and this can be reversed by both the VR1 receptor antagonist capsazepine and the CGRP blocker alphaCGRP8-37 in vitro. In this study we used intravital microscopy to look at the possible role of the VR1 receptor in the trigeminovascular system in producing dilation of dural blood vessels. Capsazepine (3 mg kg-1) was given to study the effect of the VR1 receptor in dural vessel dilation produced by either electrical stimulation, CGRP (1 microg x kg-1) or capsaicin (7 microg x kg-1) bolus injection. We also looked at the effect of the CGRP blocker alphaCGRP8-37 (300 microg x kg-1) on capsaicin-induced dilation so that we could see if the results found in vitro could also be found in vivo. Electrical stimulation of the dura mater produced a robust vasodilator response between 130 and 137% of baseline diameter that was no different across four repeat stimuli (F3,18=0.6, P=0.61). CGRP similarly produced a dilatation of 99-111% that was no different across four baseline infusions (F3,15=2.4, P=0.113). Capsaicin also produced a consistent dilation of between 112 and 120% of baseline across three injections (F2,10=0.6, P=0.567). Capsazepine did not inhibit the dilation brought about by either electrical stimulation or CGRP injection, while it was able to inhibit the dilation brought about by capsaicin (t5=3.4, P0.05). AlphaCGRP8-37 also inhibited the capsaicin-induced dilation (t5=7.4, P0.05) probably inhibiting the action of released CGRP at the CGRP receptor. The study demonstrates that capsaicin can repeatedly induce dural vessel dilation in vivo, presumably through inducing CGRP release from trigeminal sensory nerve fibres, while C-fibres may have been desensitised. The data imply that the VR1 receptor plays only a minor role in trigeminovascular-induced dural vessel dilation.

1. The detailed pathophysiology of migraine is beginning to be understood and is likely to involve activation of trigeminovascular afferents. 2. Clinically effective anti-migraine compounds are believed to have actions that include peripheral inhibition of calcitonin gene-related peptide (CGRP) release from trigeminal neurones, or preventing dural vessel dilation, or both. CGRP antagonists can block both neurogenic and CGRP-induced dural vessel dilation. 3. Nitric oxide (NO) can induce headache in migraine patients and often triggers a delayed migraine. The initial headache is thought to be caused via a direct action of the NO-cGMP pathway that causes vasodilation by vascular smooth muscle relaxation, while the delayed headache is likely to be a result of triggering trigeminovascular activation. Nitric oxide synthase (NOS) inhibitors are effective in the treatment of acute migraine. 4. The present studies used intravital microscopy to examine the effects of specific NOS inhibitors on neurogenic dural vasodilation (NDV) and CGRP-induced dilation. 5. The non-specific and neuronal NOS (nNOS) inhibitors were able to partially inhibit NDV, while the non-specific and endothelial NOS (eNOS) inhibitors were able to partially inhibit the CGRP induced dilation. 6. There was no effect of the inducible NOS (iNOS) inhibitor. 7. The data suggest that the delayed headache response triggered by NO donors in humans may be due, in part, to increased nNOS activity in the trigeminal system that causes CGRP release and dural vessel dilation. 8. Further, eNOS activity in the endothelium causes NO production and smooth muscle relaxation by direct activation of the NO-cGMP pathway, and may be involved in the initial headache response.