Abstract
An understanding of migraine must be based on data concerning the anatomy and physiology of the pain-sensitive intracranial structures. Stimulation of the superior sagittal sinus produces changes in brain blood flow and changes in neuropeptide levels similar to those seen in humans during migraine. To better understand the anatomy of the central ramifications of pain-sensitive intracranial structures we have examined the distribution of c-fos immunoreactivity in the monkey when the sinus is stimulated. Six adult Macaca nemestrina monkeys were anaesthetised. The superior sagittal sinus was isolated after a midline craniotomy and a paraffin well created. At 24 h after completion of the surgery the sinus was stimulated electrically for 1 h and the brain subsequently removed and processed for c-fos. In control animals in which the sinus was isolated but not stimulated there was a small amount of c-fos expression in the caudal brainstem and upper cervical spinal cord. Stimulation of the superior sagittal sinus evoked expression of c-fos in the caudal superfical laminae of the trigeminal nucleus and in superficial laminae of the dorsal horn of the C1 level of the upper cervical spinal cord. A lesser amount of c-fos was seen at C2 while no significant labelling above control was observed at C3. These data, while largely confirming the results from the cat concerning the central distribution trigeminovascular afferents, underscore a possibly unique specialisation of trigeminovascular afferents at the C1 level. Given the close evolutionary relationship of the monkey to man it is likely that the cells described in this study represent for primates the nucleus that mediates the pain of migraine.
Keywords: Vasculature, trigeminal nerve, migraine
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- Altschuler S. M., Bao X. M., Bieger D., Hopkins D. A., Miselis R. R. Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts. J Comp Neurol. 1989 May 8;283(2):248–268. doi: 10.1002/cne.902830207. [DOI] [PubMed] [Google Scholar]
- Anton F., Herdegen T., Peppel P., Leah J. D. c-FOS-like immunoreactivity in rat brainstem neurons following noxious chemical stimulation of the nasal mucosa. Neuroscience. 1991;41(2-3):629–641. doi: 10.1016/0306-4522(91)90355-r. [DOI] [PubMed] [Google Scholar]
- Arbab M. A., Delgado T., Wiklund L., Svendgaard N. A. Brain stem terminations of the trigeminal and upper spinal ganglia innervation of the cerebrovascular system: WGA-HRP transganglionic study. J Cereb Blood Flow Metab. 1988 Feb;8(1):54–63. doi: 10.1038/jcbfm.1988.8. [DOI] [PubMed] [Google Scholar]
- Arvidsson J., Grant G. Further observations on transganglionic degeneration in trigeminal primary sensory neurons. Brain Res. 1979 Feb 16;162(1):1–12. doi: 10.1016/0006-8993(79)90750-9. [DOI] [PubMed] [Google Scholar]
- Bullitt E. Expression of c-fos-like protein as a marker for neuronal activity following noxious stimulation in the rat. J Comp Neurol. 1990 Jun 22;296(4):517–530. doi: 10.1002/cne.902960402. [DOI] [PubMed] [Google Scholar]
- Burton H., Craig A. D., Jr Distribution of trigeminothalamic projection cells in cat and monkey. Brain Res. 1979 Feb 9;161(3):515–521. doi: 10.1016/0006-8993(79)90680-2. [DOI] [PubMed] [Google Scholar]
- Davis K. D., Dostrovsky J. O. Activation of trigeminal brain-stem nociceptive neurons by dural artery stimulation. Pain. 1986 Jun;25(3):395–401. doi: 10.1016/0304-3959(86)90244-7. [DOI] [PubMed] [Google Scholar]
- Drummond P. D., Gonski A., Lance J. W. Facial flushing after thermocoagulation of the Gasserian ganglion. J Neurol Neurosurg Psychiatry. 1983 Jul;46(7):611–616. doi: 10.1136/jnnp.46.7.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FEINDEL W., PENFIELD W., McNAUGHTON F. The tentorial nerves and Iocalization of intracranial pain in man. Neurology. 1960 Jun;10:555–563. doi: 10.1212/wnl.10.6.555. [DOI] [PubMed] [Google Scholar]
- Fukuda H., Koga T. The Bötzinger complex as the pattern generator for retching and vomiting in the dog. Neurosci Res. 1991 Dec;12(4):471–485. doi: 10.1016/s0168-0102(09)80001-1. [DOI] [PubMed] [Google Scholar]
- Goadsby P. J., Duckworth J. W. Effect of stimulation of trigeminal ganglion on regional cerebral blood flow in cats. Am J Physiol. 1987 Aug;253(2 Pt 2):R270–R274. doi: 10.1152/ajpregu.1987.253.2.R270. [DOI] [PubMed] [Google Scholar]
- Goadsby P. J., Edvinsson L., Ekman R. Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol. 1988 Feb;23(2):193–196. doi: 10.1002/ana.410230214. [DOI] [PubMed] [Google Scholar]
- Goadsby P. J., Edvinsson L., Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990 Aug;28(2):183–187. doi: 10.1002/ana.410280213. [DOI] [PubMed] [Google Scholar]
- Goadsby P. J., Hoskin K. L. Inhibition of trigeminal neurons by intravenous administration of the serotonin (5HT)1B/D receptor agonist zolmitriptan (311C90): are brain stem sites therapeutic target in migraine? Pain. 1996 Oct;67(2-3):355–359. doi: 10.1016/0304-3959(96)03118-1. [DOI] [PubMed] [Google Scholar]
- Goadsby P. J., Zagami A. S., Lambert G. A. Neural processing of craniovascular pain: a synthesis of the central structures involved in migraine. Headache. 1991 Jun;31(6):365–371. doi: 10.1111/j.1526-4610.1991.hed3106365.x. [DOI] [PubMed] [Google Scholar]
- Goadsby P. J., Zagami A. S. Stimulation of the superior sagittal sinus increases metabolic activity and blood flow in certain regions of the brainstem and upper cervical spinal cord of the cat. Brain. 1991 Apr;114(Pt 2):1001–1011. doi: 10.1093/brain/114.2.1001. [DOI] [PubMed] [Google Scholar]
- Hammond D. L., Presley R., Gogas K. R., Basbaum A. I. Morphine or U-50,488 suppresses Fos protein-like immunoreactivity in the spinal cord and nucleus tractus solitarii evoked by a noxious visceral stimulus in the rat. J Comp Neurol. 1992 Jan 8;315(2):244–253. doi: 10.1002/cne.903150210. [DOI] [PubMed] [Google Scholar]
- Hayashi H., Tabata T. Distribution of trigeminal sensory nucleus neurons projecting to the mesencephalic parabrachial area of the cat. Neurosci Lett. 1991 Jan 14;122(1):75–78. doi: 10.1016/0304-3940(91)90197-2. [DOI] [PubMed] [Google Scholar]
- Hoskin K. L., Kaube H., Goadsby P. J. Central activation of the trigeminovascular pathway in the cat is inhibited by dihydroergotamine. A c-Fos and electrophysiological study. Brain. 1996 Feb;119(Pt 1):249–256. doi: 10.1093/brain/119.1.249. [DOI] [PubMed] [Google Scholar]
- Hu J. W., Dostrovsky J. O., Sessle B. J. Functional properties of neurons in cat trigeminal subnucleus caudalis (medullary dorsal horn). I. Responses to oral-facial noxious and nonnoxious stimuli and projections to thalamus and subnucleus oralis. J Neurophysiol. 1981 Feb;45(2):173–192. doi: 10.1152/jn.1981.45.2.173. [DOI] [PubMed] [Google Scholar]
- Kalia M., Mesulam M. M. Brain stem projections of sensory and motor components of the vagus complex in the cat: II. Laryngeal, tracheobronchial, pulmonary, cardiac, and gastrointestinal branches. J Comp Neurol. 1980 Sep 15;193(2):467–508. doi: 10.1002/cne.901930211. [DOI] [PubMed] [Google Scholar]
- Kaube H., Hoskin K. L., Goadsby P. J. Activation of the trigeminovascular system by mechanical distension of the superior sagittal sinus in the cat. Cephalalgia. 1992 Jun;12(3):133–136. doi: 10.1046/j.1468-2982.1992.1203133.x. [DOI] [PubMed] [Google Scholar]
- Kaube H., Keay K. A., Hoskin K. L., Bandler R., Goadsby P. J. Expression of c-Fos-like immunoreactivity in the caudal medulla and upper cervical spinal cord following stimulation of the superior sagittal sinus in the cat. Brain Res. 1993 Nov 26;629(1):95–102. doi: 10.1016/0006-8993(93)90486-7. [DOI] [PubMed] [Google Scholar]
- Keay K. A., Bandler R. Anatomical evidence for segregated input from the upper cervical spinal cord to functionally distinct regions of the periaqueductal gray region of the cat. Neurosci Lett. 1992 May 25;139(2):143–148. doi: 10.1016/0304-3940(92)90538-i. [DOI] [PubMed] [Google Scholar]
- Killackey H. P., Erzurumlu R. S. Trigeminal projections to the superior colliculus of the rat. J Comp Neurol. 1981 Sep 10;201(2):221–242. doi: 10.1002/cne.902010207. [DOI] [PubMed] [Google Scholar]
- Lambert G. A., Bogduk N., Goadsby P. J., Duckworth J. W., Lance J. W. Decreased carotid arterial resistance in cats in response to trigeminal stimulation. J Neurosurg. 1984 Aug;61(2):307–315. doi: 10.3171/jns.1984.61.2.0307. [DOI] [PubMed] [Google Scholar]
- Lambert G. A., Goadsby P. J., Zagami A. S., Duckworth J. W. Comparative effects of stimulation of the trigeminal ganglion and the superior sagittal sinus on cerebral blood flow and evoked potentials in the cat. Brain Res. 1988 Jun 21;453(1-2):143–149. doi: 10.1016/0006-8993(88)90152-7. [DOI] [PubMed] [Google Scholar]
- Liu-Chen L. Y., Han D. H., Moskowitz M. A. Pia arachnoid contains substance P originating from trigeminal neurons. Neuroscience. 1983 Aug;9(4):803–808. doi: 10.1016/0306-4522(83)90268-3. [DOI] [PubMed] [Google Scholar]
- Martin G. F., Cabana T., Ditirro F. J., Ho R. H., Humbertson A. O., Jr Raphespinal projections in the North American opossum: evidence for connectional heterogeneity. J Comp Neurol. 1982 Jun 10;208(1):67–84. doi: 10.1002/cne.902080106. [DOI] [PubMed] [Google Scholar]
- Mayberg M. R., Zervas N. T., Moskowitz M. A. Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry. J Comp Neurol. 1984 Feb 10;223(1):46–56. doi: 10.1002/cne.902230105. [DOI] [PubMed] [Google Scholar]
- Mayberg M., Langer R. S., Zervas N. T., Moskowitz M. A. Perivascular meningeal projections from cat trigeminal ganglia: possible pathway for vascular headaches in man. Science. 1981 Jul 10;213(4504):228–230. doi: 10.1126/science.6166046. [DOI] [PubMed] [Google Scholar]
- Menétrey D., Basbaum A. I. Spinal and trigeminal projections to the nucleus of the solitary tract: a possible substrate for somatovisceral and viscerovisceral reflex activation. J Comp Neurol. 1987 Jan 15;255(3):439–450. doi: 10.1002/cne.902550310. [DOI] [PubMed] [Google Scholar]
- Menétrey D., Chaouch A., Binder D., Besson J. M. The origin of the spinomesencephalic tract in the rat: an anatomical study using the retrograde transport of horseradish peroxidase. J Comp Neurol. 1982 Apr 1;206(2):193–207. doi: 10.1002/cne.902060208. [DOI] [PubMed] [Google Scholar]
- Menétrey D., Gannon A., Levine J. D., Basbaum A. I. Expression of c-fos protein in interneurons and projection neurons of the rat spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol. 1989 Jul 8;285(2):177–195. doi: 10.1002/cne.902850203. [DOI] [PubMed] [Google Scholar]
- Nahin R. L., Madsen A. M., Giesler G. J., Jr Anatomical and physiological studies of the gray matter surrounding the spinal cord central canal. J Comp Neurol. 1983 Nov 1;220(3):321–335. doi: 10.1002/cne.902200306. [DOI] [PubMed] [Google Scholar]
- Nozaki K., Moskowitz M. A., Boccalini P. CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges. Br J Pharmacol. 1992 Jun;106(2):409–415. doi: 10.1111/j.1476-5381.1992.tb14348.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peschanski M., Ralston H. J., 3rd Light and electron microscopic evidence of transneuronal labeling with WGA-HRP to trace somatosensory pathways to the thalamus. J Comp Neurol. 1985 Jun 1;236(1):29–41. doi: 10.1002/cne.902360104. [DOI] [PubMed] [Google Scholar]
- REXED B. A cytoarchitectonic atlas of the spinal cord in the cat. J Comp Neurol. 1954 Apr;100(2):297–379. doi: 10.1002/cne.901000205. [DOI] [PubMed] [Google Scholar]
- Ruskell G. L., Simons T. Trigeminal nerve pathways to the cerebral arteries in monkeys. J Anat. 1987 Dec;155:23–37. [PMC free article] [PubMed] [Google Scholar]
- Rustioni A., Sanyal S., Kuypers H. G. A histochemical study of the distribution of the trigeminal divisions in the substantia gelatinosa of the rat. Brain Res. 1971 Sep 10;32(1):45–52. doi: 10.1016/0006-8993(71)90154-5. [DOI] [PubMed] [Google Scholar]
- Sagar S. M., Sharp F. R., Curran T. Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science. 1988 Jun 3;240(4857):1328–1331. doi: 10.1126/science.3131879. [DOI] [PubMed] [Google Scholar]
- Shepheard S. L., Williamson D. J., Williams J., Hill R. G., Hargreaves R. J. Comparison of the effects of sumatriptan and the NK1 antagonist CP-99,994 on plasma extravasation in Dura mater and c-fos mRNA expression in trigeminal nucleus caudalis of rats. Neuropharmacology. 1995 Mar;34(3):255–261. doi: 10.1016/0028-3908(94)00153-j. [DOI] [PubMed] [Google Scholar]
- Shigenaga Y., Chen I. C., Suemune S., Nishimori T., Nasution I. D., Yoshida A., Sato H., Okamoto T., Sera M., Hosoi M. Oral and facial representation within the medullary and upper cervical dorsal horns in the cat. J Comp Neurol. 1986 Jan 15;243(3):388–408. doi: 10.1002/cne.902430309. [DOI] [PubMed] [Google Scholar]
- Shigenaga Y., Nakatani Z., Nishimori T., Suemune S., Kuroda R., Matano S. The cells of origin of cat trigeminothalamic projections: especially in the caudal medulla. Brain Res. 1983 Oct 31;277(2):201–222. doi: 10.1016/0006-8993(83)90928-9. [DOI] [PubMed] [Google Scholar]
- Strassman A. M., Mineta Y., Vos B. P. Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat. J Neurosci. 1994 Jun;14(6):3725–3735. doi: 10.1523/JNEUROSCI.14-06-03725.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strassman A., Mason P., Moskowitz M., Maciewicz R. Response of brainstem trigeminal neurons to electrical stimulation of the dura. Brain Res. 1986 Aug 6;379(2):242–250. doi: 10.1016/0006-8993(86)90777-8. [DOI] [PubMed] [Google Scholar]
- Tran Dinh Y. R., Thurel C., Cunin G., Serrie A., Seylaz J. Cerebral vasodilation after the thermocoagulation of the trigeminal ganglion in humans. Neurosurgery. 1992 Oct;31(4):658–663. doi: 10.1227/00006123-199210000-00007. [DOI] [PubMed] [Google Scholar]
- Wiberg M., Westman J., Blomqvist A. The projection to the mesencephalon from the sensory trigeminal nuclei. An anatomical study in the cat. Brain Res. 1986 Dec 3;399(1):51–68. doi: 10.1016/0006-8993(86)90600-1. [DOI] [PubMed] [Google Scholar]
- Zagami A. S., Goadsby P. J., Edvinsson L. Stimulation of the superior sagittal sinus in the cat causes release of vasoactive peptides. Neuropeptides. 1990 Jun;16(2):69–75. doi: 10.1016/0143-4179(90)90114-e. [DOI] [PubMed] [Google Scholar]
- Zagami A. S., Lambert G. A. Stimulation of cranial vessels excites nociceptive neurones in several thalamic nuclei of the cat. Exp Brain Res. 1990;81(3):552–566. doi: 10.1007/BF02423504. [DOI] [PubMed] [Google Scholar]