Intravital microscopy on a closed cranial window in mice: a model to study trigeminovascular mechanisms involved in migraine.
The purpose of the study was to develop a mouse model to study trigeminovascular mechanisms using intravital microscopy on a closed cranial window. In addition, we studied exogenous and endogenous calcitonin gene-related peptide (CGRP)-mediated vasodilation in dural arteries. Arteries in C57BL/6Jico mice were constricted with endothelin-1, which reduced the baseline diameter by 65-75%. Subsequently, vasodilation was induced by alpha-CGRP, capsaicin or transcranial electrical stimulation of perivascular trigeminal nerves in the absence or presence of different concentrations of BIBN4096BS or sumatriptan. Both alpha-CGRP and capsaicin induced vasodilation in preconstricted arteries. Transcranial electrical stimulation also induced current-dependent relaxation of dural arteries with 100 microA producing maximal dilation in the control group. BIBN4096BS blocked the responses evoked by alpha-CGRP and capsaicin, as well as electrical stimulation, whereas sumatriptan attenuated only vasodilation induced by electrical stimulation. This model is likely to prove useful in dissecting elements of the trigeminovascular system and for exploring pathophysiological aspects of migraine, especially in future studies using transgenic mice with mutations relevant to those observed in patients with migraine.
Gupta
S
S
Department of Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.
Akerman
S
S
van den Maagdenberg
A M J M
AM
Saxena
P R
PR
Goadsby
P J
PJ
van den Brink
A M
AM
D000818:Animals; D001158:Arteries / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004388:Dura Mater / Q000098:blood supply* / Q000187:drug effects; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video / Q000379:methods*; D008881:Migraine Disorders / Q000503:physiopathology*; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012886:Skull; D018170:Sumatriptan / Q000494:pharmacology; D014275:Trigeminal Caudal Nucleus / Q000187:drug effects / Q000503:physiopathology*; D014664:Vasodilation
D010879:Piperazines; D011799:Quinazolines; D017366:Serotonin Receptor Agonists; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; C406305:olcegepant