Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries

Trigeminal sensory innervation of cerebral vessels and the surrounding dura is responsible for most intracranial head pain. Small-diameter fibers containing substance P (Sub P) have been observed in the periadventitia around feline cerebral blood vessels, and it has been suggested that these fibers are the trigeminal substrate for vascular pain associated with cluster and migraine headaches. Calcitonin gene related peptide (CGRP) coexists with Sub P in some of these fibers and with some Sub P containing neurons in the trigeminal ganglion. In addition, a population of trigeminal neurons containing CGRP but not Sub P has been observed. We now report that the population of trigeminal ganglion cells projecting to the cerebral vasculature is enriched in CGRP-containing neurons, and especially in the population of neurons containing CGRP and not Sub P. Using retrograde tracing of fluorescent tracers combined with immunocytochemistry after explant culture, we found approximately 32% of trigeminal ganglion cells projecting to the cerebral vasculature contained CGRP. Approximately 18 and 17% of these cells contained Sub P and cholecystokinin (CCK), respectively. The 32% of ganglion cells projecting to the cerebral vasculature that contain CGRP stands in contrast to the 12% CGRP positive seen in the population of ganglion cells projecting out to another target (the forehead), and the 21 and 23% CGRP positive observed in the mandibular branch and entire ganglion, respectively. Sub P and CCK are not enriched in the trigeminal innervation of the vasculature compared with their presence in cells throughout the ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  G. Greeley,et al.  Colocalization of Calcitonin Gene‐Related Peptide and Somatostatin in Pancreatic Islet Cells and Inhibition of Insulin Secretion by Calcitonin Gene‐Related Peptide in the Rat , 1988, Pancreas.

[2]  I. Black,et al.  Biochemistry of information storage in the nervous system. , 1987, Science.

[3]  D. Kooy,et al.  Catecholamine and serotonin colocalization in projection neurons of the area postrema , 1987, Brain Research.

[4]  G. Dockray,et al.  Calcitonin gene-related peptide and substance P in afferents to the upper gastrointestinal tract in the rat , 1987, Neuroscience Letters.

[5]  E. Frank,et al.  Peripheral specification of sensory neurons transplanted to novel locations along the neuraxis , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  J. Trojanowski,et al.  A quantitative correlation of substance P-, calcitonin gene-related peptide- and cholecystokinin-like immunoreactivity with retrogradely labeled trigeminal ganglion cells innervating the eye , 1987, Brain Research.

[7]  H. Takagi,et al.  Calcitonin gene-related peptide promotes mechanical nociception by potentiating release of substance P from the spinal dorsal horn in rats , 1987, Brain Research.

[8]  M. Moskowitz,et al.  Substance P-like immunoreactivity in rat forebrain leptomeninges and cerebral vessels originates from the trigeminal but not sympathetic ganglia , 1987, Brain Research.

[9]  S. McMahon,et al.  Peptide expression is altered when afferent nerves reinnervate inappropriate tissue , 1987, Neuroscience Letters.

[10]  M. Moskowitz,et al.  In vitro evidence that vasoactive intestinal peptide is a transmitter of neuro-vasodilation in the head of the cat , 1986, Neuroscience.

[11]  J. Lance,et al.  Stimulation of the Trigeminal ganglion increases flow in the extracerebral but not the cerebral circulation of the monkey , 1986, Brain Research.

[12]  P. Mason,et al.  Response of brainstem trigeminal neurons to electrical stimulation of the dura , 1986, Brain Research.

[13]  J. Mcculloch,et al.  Calcitonin gene-related peptide: functional role in cerebrovascular regulation. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[14]  D. van der Kooy,et al.  Pattern of intracranial and extracranial projections of trigeminal ganglion cells , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  J. Polak,et al.  Calcitonin gene-related peptide immunoreactivity in afferent neurons supplying the urinary tract: Combined retrograde tracing and immunohistochemistry , 1986, Neuroscience.

[16]  J. Dostrovsky,et al.  Activation of trigeminal brain-stem nociceptive neurons by dural artery stimulation , 1986, Pain.

[17]  D. van der Kooy,et al.  Cell death organizes the postnatal development of the trigeminal innervation of the cerebral vasculature. , 1986, Brain research.

[18]  L. Liu-Chen,et al.  Immunoelectron microscopic study of substance P-containing fibers in feline cerebral arteries , 1986, Brain Research.

[19]  P. Emson,et al.  Origins and distribution of calcitonin gene-related peptide-containing nerves in the wall of the cerebral arteries of the guinea pig with special reference to the coexistence with substance P , 1986, Brain Research.

[20]  R. Stone,et al.  Neuropeptide immunoreactivity of pericellular baskets in the guinea pig trigeminal ganglion , 1986, Neuroscience Letters.

[21]  J. Polak,et al.  Calcitonin gene-related peptide-immunoreactive nerves in the tongue, epiglottis and pharynx of the rat: Occurrence, distribution and origin , 1986, Brain Research.

[22]  M. Moskowitz,et al.  Some cholecystokinin-8 immunoreactive fibers in large pial arteries originate from trigeminal ganglion , 1985, Brain Research.

[23]  M. Moskowitz,et al.  Trigeminal afferents to cerebral arteries and forehead are not divergent axon collaterals in cat , 1985, Neuroscience Letters.

[24]  P. Emson,et al.  Distribution of calcitonin gene-related peptide in the rat peripheral nervous system with reference to its coexistence with substance P , 1985, Neuroscience.

[25]  D. Jacobowitz,et al.  Calcitonin gene-related peptide coexists with substance P in capsaicin sensitive neurons and sensory ganglia of the rat , 1985, Peptides.

[26]  M. Costa,et al.  Co-localization of calcitonin gene-related peptide-like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons of guinea pigs , 1985, Neuroscience Letters.

[27]  F. Sundler,et al.  Calcitonin gene-related peptide is present in mammalian cerebrovascular nerve fibres and dilates pial and peripheral arteries , 1985, Neuroscience Letters.

[28]  P. Emson,et al.  Fine structure of peptidergic and catecholaminergic nerve fibers in the anterior cerebral artery and their interrelationship: An immunoelectron microscopic study , 1985, The Journal of comparative neurology.

[29]  J. M. Butler,et al.  Distribution and origin of calcitonin gene‐related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye , 1985, The Journal of comparative neurology.

[30]  P. Emson,et al.  Coexistence of calcitonin gene-related peptide and substance P-like peptide in single cells of the trigeminal ganglion of the rat: immunohistochemical analysis , 1985, Brain Research.

[31]  D. Jacobowitz,et al.  Origin of cholinergic nerves to the rat major cerebral arteries: Coexistence with vasoactive intestinal polypeptide , 1985, Brain Research Bulletin.

[32]  V. Seybold,et al.  Immunohistochemical studies of substance P, cholecystokinin-octapeptide and somatostatin in dorsal root ganglia of the rat , 1985, Neuroscience.

[33]  J. Hardebo The Involvement of Trigeminal Substance P Neurons in Cluster Headache. An Hypothesis , 1984, Headache.

[34]  S. Amara,et al.  Alternative RNA processing: determining neuronal phenotype. , 1984, Science.

[35]  M. Moskowitz The neurobiology of vascular head pain , 1984, Annals of neurology.

[36]  M. Moskowitz,et al.  Co‐localization of retrogradely transported wheat germ agglutinin and the putative neurotransmitter substance P within trigeminal ganglion cells projecting to cat middle cerebral artery , 1984, The Journal of comparative neurology.

[37]  M. Moskowitz,et al.  Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry , 1984, The Journal of comparative neurology.

[38]  P. Emson,et al.  Neuropeptide Y: Cerebrovascular innervation an vasomotor effects in the cat , 1983, Neuroscience Letters.

[39]  D. Duverger,et al.  Central serotonergic nerves project to the pial vessels of the brain , 1983, Nature.

[40]  L. Swanson,et al.  Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing , 1983, Nature.

[41]  M. Moskowitz,et al.  Immunohistochemical evidence for a substance P-containing trigeminovascular pathway to pial arteries in cats , 1983, Brain Research.

[42]  M. Moskowitz,et al.  Do intracranial and extracranial trigeminal afferents represent divergent axon collaterals? , 1983, Neuroscience Letters.

[43]  A. Mudge,et al.  A subpopulation of rat dorsal root ganglion neurones is catecholaminergic , 1983, Nature.

[44]  T. Hökfelt,et al.  Coexistence of cholecystokinin- and substance P-like peptides in neurons of the dorsal root ganglia of the rat , 1982, Neuroscience Letters.

[45]  J. Barker,et al.  Localization of immunoreactive dynorphin in neurons cultured from spinal cord and dorsal root ganglia. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[46]  H. Steiger,et al.  The sensory representation of the dura mater in the trigeminal ganglion of the cat , 1982, Neuroscience Letters.

[47]  J. Mcculloch,et al.  Substance P: immunohistochemical localization and effect upon cat pial arteries in vitro and in situ. , 1981, The Journal of physiology.

[48]  M. Moskowitz,et al.  Perivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man. , 1981, Science.

[49]  B. Gazelius,et al.  Vasodilatation in the dental pulp produced by electrical stimulation of the inferior alveolar nerve in the cat. , 1980, Acta physiologica Scandinavica.

[50]  G. Nilsson,et al.  Release of substance P-like immunoreactivity from the dental pulp. , 1977, Acta physiologica Scandinavica.

[51]  F. P. Wirth,et al.  Referral of pain from dural stimulation in man. , 1971, Journal of neurosurgery.

[52]  W. Penfield,et al.  DURAL HEADACHE AND INNERVATION OF THE DURA MATER , 1940 .

[53]  T. Fay LXXX. Atypical Facial Neuralgia, a Syndrome of Vascular Pain , 1932 .

[54]  A. Davies,et al.  Earliest sensory nerve fibres are guided to peripheral targets by attractants other than nerve growth factor , 1983, Nature.

[55]  P. Patterson Environmental determination of autonomic neurotransmitter functions. , 1978, Annual review of neuroscience.

[56]  H. Wolff,et al.  EXPERIMENTAL STUDIES ON HEADACHE , 1942 .