title: Colocalization of CGRP with 5-HT1B/1D receptors and substance P in trigeminal ganglion neurons in rats.
abstract: Vasodilatation in the dura mater has been implicated in migraine pathogenesis. Anti-migraine triptan drugs block vasodilatation by binding to 5-HT1B/1D receptors localized on the peripheral sensory terminals and dural blood vessel smooth muscles. Previous studies suggest that calcitonin gene-related peptide (CGRP) released from Adelta-fibres plays a more important role than substance P (SP) released from C-fibres in inducing dural vasodilatation and that one of the antimigraine mechanisms of triptan drugs is inhibiting CGRP release. In the present study, the relationship between CGRP and 5-HT1B/1D receptors, and between CGRP and SP in the trigeminal ganglion neurons in rats was examined by double immunohistochemical staining. CGRP, 5-HT1B, 5-HT1D and SP-positive trigeminal ganglion neurons were all predominantly small and medium-sized. In the trigeminal ganglia, approximately 50% of CGRP-positive neurons were 5-HT1B positive. Similarly, approximately 55% of CGRP-positive neurons were 5-HT1D immunoreactive. Approximately 50% of CGRP-positive neurons were SP-positive, while 93% of SP-positive neurons were CGRP-positive, suggesting that nearly all SP-positive neurons also contain CGRP. The fibre types of the 5-HT1B- and 5-HT1D-positive neurons were further investigated with an antibody against the A-fibre marker 200-kDa neurofilaments (NF200). Approximately 46% of the 5-HT1B-positive and 43% of the 5-HT1D-positive trigeminal ganglion neurons were also NF200 positive, indicating that many A-fibre trigeminal neurons express 5-HT1B or 5-HT1D receptors. These results support the hypothesis that one important action of antimigraine drugs is the inhibition of CGRP release and that Adelta-fibres may play an important role in migraine pathogenesis.
authors: Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow CM20 2QR, UK. qingping_ma@merck.com
authors: Q P
authors: QP
authors: Ma
authors: R
authors: R
authors: Hill
authors: D
authors: D
authors: Sirinathsinghji
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D004388:Dura Mater / Q000098:blood supply / Q000503:physiopathology; D005455:Fluorescent Antibody Technique; D008576:Meningeal Arteries / Q000294:innervation / Q000503:physiopathology; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009412:Nerve Fibers / Q000378:metabolism / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology
chemical_list: D016900:Neurofilament Proteins; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide