title: Innervation of rat and human dura mater and pericranial tissues in the parieto-temporal region by meningeal afferents.
abstract: OBJECTIVE
  To reinvestigate the innervation pattern of the dura mater of rat and human middle cranial fossa, the morpho-functional substrate of headache generation, and adjacent extracranial tissues with neuronal in vitro tracing.
  
  
  BACKGROUND
  This study was initiated by recent structural and functional findings of meningeal afferent fibers which innervate the cranial dura mater and may project to extracranial tissues.
  
  
  METHODS
  Anterograde and retrograde neuronal in vitro tracing was made in formaldehyde fixed hemisected rat and human skulls. The fluorescent tracer DiI was applied to proximally cut meningeal nerves in rat and to distal branches of the spinosus nerve in human calvaria lined by dura mater. After several weeks, the dura mater and deep extracranial tissues were examined with fluorescence microscopy.
  
  
  RESULTS
  In addition to a network of meningeal nerve fibers, several fiber bundles were observed, leaving the skull through emissary canals and fissures to innervate the pericranial temporal, parietal, and occipital periosteum. Traced fibers were seen spreading into deep layers of the temporal and upper neck muscles. Retrograde neuronal tracing revealed labeled cell bodies exclusively in the mandibular and maxillary division of the rat trigeminal ganglion, and centrally projecting fibers were identified in the spinal trigeminal tract. Electron microscopy of the cross-sected spinosus nerve showed myelinated and unmyelinated axons with similar numbers in human and rat.
  
  
  CONCLUSIONS
  We conclude that a proportion of meningeal afferents innervates extracranial tissues like periosteum and pericranial muscles via collaterals projecting through the skull. These afferents may be nociceptive, some may subserve proprioceptive functions. The finding of extracranial projections of meningeal afferents may be important for our understanding of extracranial impacts on headache generation and therapy.
authors.affiliation: Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany; Department of Nephrology and Hypertensiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schueler
authors.forename: Winfried L
authors.initials: WL
authors.lastname: Neuhuber
authors.forename: Roberto
authors.initials: R
authors.lastname: De Col
authors.forename: Karl
authors.initials: K
authors.lastname: Messlinger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002102:Cadaver; D035301:Cranial Fossa, Middle / Q000294:innervation*; D004388:Dura Mater / Q000033:anatomy & histology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation*; D009475:Neurons, Afferent / Q000166:cytology*; D010521:Periosteum / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar
keywords: DiI; fluorescence microscopy; headache; neuronal in vitro tracing; spinosus nerve; trigeminal ganglion