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Topic: Fresh Research - Goadsby & CGRP (Read 362 times) |
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floridian
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More work from Dr. Goadsby on CGRP, a naturally produced compound that is elevated in migraine and cluster headache. This abstract describes a pretty complex animal model for experimenting with CGRP. The upshot - more evidence that blocking CGRP may be a good way to treat cluster and migraine, more evidence that glutamate aggravates these headaches.
Other links:
http://headaches.about.com/cs/druginfo/a/cgrp_intro.htm
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed &dopt=Abstract&list_uids=12818465
Quote:Br J Pharmacol. 2004 Jul 5 [Epub ahead of print]
Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat.
Storer RJ, Akerman S, Goadsby PJ.
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 alpha-CGRP-(8-37) and BIBN4096BS. Cats were anaesthetised with alpha-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 alpha-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. alpha-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 micro g 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. |
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