Messenger molecules and receptor mRNA in the human trigeminal ganglion

Tajti, János; Uddman, Rolf; Möller, Sebastian; Sundler, F.; Edvinsson, Lars

doi:10.1016/s0165-1838(99)00024-7

Cited by 182 publications

(132 citation statements)

References 57 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…We observed that neurons positive for CGRP were mostly negative for the receptor components CLR and RAMP1. Almost 50% of human trigeminal neurons expressed CGRP, which is in agreement with previous studies in man (Tajti et al, 1999) and rat (Ma et al, 2001, Lennerz et al, 2008. Expression of CLR and RAMP1 was seen in approximately 40% of the neurons.…”

Section: The Distribution Of Cgrp and The Receptor Componentssupporting

confidence: 91%

“…Taken together, the release of CGRP from trigeminal neurons seems to play an important role in migraine pathophysiology, in both initiating and sustaining migraine attacks. Previous studies have shown both protein and mRNA levels of CGRP within human and rat trigeminal ganglia (Edvinsson et al, 1998, Tajti et al, 1999, Hou et al, 2001, Li et al, 2008.…”

Section: The Distribution Of Cgrp and The Receptor Componentsmentioning

confidence: 92%

“…Earlier it was believed that the main function of glial cells was that of neuronal support; however during the last decade it has been revealed that the satellite glial cells may modulate neuronal function and activity, and could therefore be a factor in migraine pathophysiology (Hanani, 2005, Dublin and Hanani, 2007, Thalakoti et al, 2007, Li et al, 2008 Immunohistochemical studies performed on the trigeminal system have shown CGRP immunoreactivity in about 50 % of the neurons of human and rat trigeminal ganglion (Tajti et al, 1999, Lennerz et al, 2008. The elegant work of Lennerz and co-workers also demonstrated CLR and RAMP1 within the rat trigeminal ganglion.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

et al. 2010

View full text Add to dashboard Cite

"Differential distribution of calcitonin gene-related peptide (CGRP) and CGRP receptor components (CLR and RAMP1) in the human trigeminal ganglion."Neuroscience, 2010, Jun 2 http://dx.doi.org/10.1016/j.neuroscience.2010.05.016Access to the published version may require journal subscription.Published with permission from: Elsevier Antibodies against purified CLR and RAMP1 proteins were produced and characterized for this study. Trigeminal ganglia were obtained at autopsy from adult subjects and sections from rat trigeminal ganglia were used to compare the immunostaining pattern. The number of cells expressing CGRP, CLR and RAMP1, respectively, were counted. In addition, the glial cells of trigeminal ganglion, particularly the satellite glial cell, were studied to understand a possible relation.We observed immunoreactivity for CGRP, CLR and RAMP1, in the human trigeminal ganglion: 49% of the neurons expressed CGRP, 37% CLR and 36% RAMP1. Co-localization of CGRP and the receptor components was rarely found. There were no CGRP immunoreactions in the glial cells; however some of the glial cells displayed CLR and RAMP1 immunoreactivity. Similar results were observed in rat trigeminal ganglia.We report that human and rat trigeminal neurons store CGRP, CLR and RAMP1, however, CGRP and CLR/RAMP1 do not co-localize regularly but are found in separate neurons. Glial cells also contain the CGRP receptor components but not CGRP. Our results indicate, for the first time, the possibility of CGRP signaling in the human trigeminal ganglion involving both neurons and satellite glial cells. This suggests a possible site of action for the novel CGRP receptor antagonists in migraine therapy.

show abstract

Section: The Distribution Of Cgrp and The Receptor Componentssupporting

confidence: 91%

Section: The Distribution Of Cgrp and The Receptor Componentsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Thus we could verify the location by a positive expression of the immediate early gene c-fos [30][31][32]. Immunohistochemical analysis of the trigeminal ganglion revealed that nerve cell bodies are CGRP-, SP-, NOSand PACAP-positive in humans [33]. The cell bodies in the trigeminal ganglion also contain CGRP mRNA as shown by in situ hybridization [34].…”

Section: Discussionmentioning

confidence: 85%

Immunoreactivity of NOS, CGRP, PACAP, SP and VIP in the trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2 of the cat

et al. 2003

Self Cite

View full text Add to dashboard Cite

IntroductionNeurovascular headaches, such as migraine and cluster headache, are very disabling, common disorders. Despite much progress in research during recent years both at the therapeutic level with the development of triptans and at the level of the general understanding of the basic mechanisms, there is still much to learn about these disorders [1].Nociceptive fibers on intracranial vessels such as the superior sagittal sinus (SSS) and the middle meningeal and middle cerebral arteries [2] are central in the understanding of the pathogenesis of neurovascular headache. These vessels are innervated by myelinated Aδ-and unmyelinated C-fibers from the trigeminal ganglion [3]. The system consists of bipolar neurons with cell bodies that reside in the trigeminal ganglion and project to the dura mater and the SSS as well as the major cerebral arteries at the base of the brain, while the central projection is to the trigeminal nucleus caudalis (TNC) in the caudal medulla oblongata and in the cervical spinal cord at the C1 and C2 levels [4]. J Headache Pain (2003) 4:156-163 DOI 10.1007 Immunoreactivity of NOS, CGRP, PACAP, SP and VIP in the trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2 of the cat Abstract The aim of the present study was to map the presence of neurotransmitters and nitric oxid synthase (NOS) in the trigeminal nucleus caudalis and cervical spinal cord of cat. Immunocytochemistry was used to map the presence of neuronal NOS, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase activating peptide (PACAP), substance P (SP) and vasoactive intestinal peptide (VIP). The superior sagittal sinus (SSS) was stimulated electrically for 2h (0.3 Hz, 0.25 ms duration, 120 V) to examine if this would lead to depletion of the neurotransmitters. Numerous SP-and CGRP-positive nerve fibers (but no cells) were found in the trigeminal nucleus caudalis (TNC) and in Rexed lamina I and II°of the dorsal horn at C1/C2 level of the spinal cord. Moderate amounts of PACAP-and NOS-positive nerve fibers were also seen in these areas while there were only few VIP-positive fibers. There was no observable difference in the amount of immunoreactivity of NOS or the neuropeptides between stimulated and control cats. The stimulation resulted in marked c-fos immunoreactivity in the same regions of the TNC. The bipolar trigeminal neurons project to the TNC and C1/C2 areas with fibers containing neuropeptides and NOS. Stimulation of the SSS for 2 h was not sufficient to cause noticeable depletion.

show abstract

“…The nerve fibers and the cell bodies contain a number of messenger molecules, but CGRP is the one most frequently expressed in humans. 3 Moreover, release of CGRP from perivascular nerves in the meninges (dura mater) and in the cerebral circulation 2,4 -6 has been conclusively demonstrated experimentally and shown to evoke vasodilatation and migraine.…”

Section: Introductionmentioning

confidence: 99%

CGRP Receptor Antagonism and Migraine

Edvinsson

2010

Neurotherapeutics

Self Cite

View full text Add to dashboard Cite

Summary: Calcitonin gene-related peptide (CGRP) is expressed throughout the central and peripheral nervous systems, consistent with control of vasodilatation, nociception, motor function, secretion, and olfaction. ␣CGRP is prominently localized in primary spinal afferent C and A⌬ fibers of sensory ganglia, and ␤CGRP is the main isoform in the enteric nervous system. In the CNS there is a wide distribution of CGRP-containing neurons, with the highest levels occurring in striatum, amygdala, colliculi, and cerebellum. The peripheral projections are involved in neurogenic vasodilatation and inflammation, and central release induces hyperalgesia. CGRP is released from trigeminal nerves in migraine. Trigeminal nerve activation results in antidromic release of CGRP to cause non-endothelium-mediated vasodilatation. At the central synapses in the trigeminal nucleus caudalis, CGRP acts postjunctionally on second-order neurons to transmit pain signals centrally via the brainstem and midbrain to the thalamus and higher cortical pain regions. Recently developed CGRP receptor antagonists are effective at aborting acute migraine attacks. They may act both centrally and peripherally to attenuate signaling within the trigeminovascular pathway.

show abstract

Messenger molecules and receptor mRNA in the human trigeminal ganglion

Cited by 182 publications

References 57 publications

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

Immunoreactivity of NOS, CGRP, PACAP, SP and VIP in the trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2 of the cat

CGRP Receptor Antagonism and Migraine

Contact Info

Product

Resources

About