Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat
Version of Record online: 29 JAN 2009
2004 British Pharmacological Society
British Journal of Pharmacology
Volume 142, Issue 7, pages 1171–1181, August 2004
How to Cite
Storer, R. J., Akerman, S. and Goadsby, P. J. (2004), Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. British Journal of Pharmacology, 142: 1171–1181. doi: 10.1038/sj.bjp.0705807
- Issue online: 29 JAN 2009
- Version of Record online: 29 JAN 2009
- (Received August 7, 2003, Revised January 20, 2004, Accepted March 23, 2004)
- cluster headache;
- CGRP antagonist;
- trigeminocervical complex
Calcitonin gene-related peptide (CGRP) is released into the cranial circulation of humans during acute migraine. To determine whether CGRP is involved in neurotransmission in craniovascular nociceptive pathways, we microiontophoresed onto neurons in the trigeminocervical complex and intravenously administered the CGRP receptor antagonists α-CGRP-(8–37) and BIBN4096BS.
Cats were anaesthetised with α-chloralose, and using halothane during surgical preparation. A craniotomy and C1/C2 laminectomy allowed access to the superior sagittal sinus (SSS) and recording site. Recordings of activity in the trigeminocervical complex evoked by electrical stimulation of the SSS were made. Multibarrelled micropipettes incorporating a recording electrode were used for microiontophoresis of test substances.
Cells recorded received wide dynamic range (WDR) or nociceptive specific (NS) input from cutaneous receptive fields on the face or forepaws. Cell firing was increased to 25–30 Hz by microiontophoresis of L-glutamate (n=43 cells).
Microiontophoresis of α-CGRP excited seven of 17 tested neurons.
BIBN4096BS inhibited the majority of units (26 of 38 cells) activated by L-glutamate, demonstrating a non-presynaptic site of action for CGRP. α-CGRP-(8–37) inhibited a similar proportion of units (five of nine cells).
Intravenous BIBN4096BS resulted in a dose-dependent inhibition of trigeminocervical SSS-evoked activity (ED50 31 μg kg–1). The maximal effect observed within 30 min of administration.
The data suggest that there are non-presynaptic CGRP receptors in the trigeminocervical complex that can be inhibited by CGRP receptor blockade and that a CGRP receptor antagonist would be effective in the acute treatment of migraine and cluster headache.
British Journal of Pharmacology (2004) 142, 1171–1181. doi:10.1038/sj.bjp.0705807