title: Chemosensory properties of murine nasal and cutaneous trigeminal neurons identified by viral tracing.
abstract: BACKGROUND
  Somatosensation of the mammalian head is mainly mediated by the trigeminal nerve that provides innervation of diverse tissues like the face skin, the conjunctiva of the eyes, blood vessels and the mucouse membranes of the oral and nasal cavities. Trigeminal perception encompasses thermosensation, touch, and pain. Trigeminal chemosensation from the nasal epithelia mainly evokes stinging, burning, or pungent sensations. In vitro characterization of trigeminal primary sensory neurons derives largely from analysis of complete neuronal populations prepared from sensory ganglia. Thus, functional properties of primary trigeminal afferents depending on the area of innervation remain largely unclear.
  
  
  RESULTS
  We established a PrV based tracing technique to identify nasal and cutaneous trigeminal neurons in vitro. This approach allowed analysis and comparison of identified primary afferents by means of electrophysiological and imaging measurement techniques. Neurons were challenged with several agonists that were reported to exhibit specificity for known receptors, including TRP channels and purinergic receptors. In addition, TTX sensitivity of sodium currents and IB4 binding was investigated. Compared with cutaneous neurons, a larger fraction of nasal trigeminal neurons showed sensitivity for menthol and capsaicin. These findings pointed to TRPM8 and TRPV1 receptor protein expression largely in nasal neurons whereas for cutaneous neurons these receptors are present only in a smaller fraction. The majority of nasal neurons lacked P2X3 receptor-mediated currents but showed P2X2-mediated responses when stimulated with ATP. Interestingly, cutaneous neurons revealed largely TTX resistant sodium currents. A significantly higher fraction of nasal and cutaneous afferents showed IB4 binding when compared to randomly chosen trigeminal neurons.
  
  
  CONCLUSIONS
  In conclusion, the usability of PrV mediated tracing of primary afferents was demonstrated. Using this technique it could be shown that compared with neurons innervating the skin nasal trigeminal neurons reveal pronounced chemosensitivity for TRPM8 and TRPV1 channel agonists and only partially meet properties typical for nociceptors. In contrast to P2X3 receptors, TRPM8 and TRPV1 receptors seem to be of pronounced physiological relevance for intranasal trigeminal sensation.
authors.affiliation: Lehrstuhl für Zellphysiologie, Ruhr-Universität, Bochum, Germany. Nils.Damann@RUB.de
authors.forename: Nils
authors.initials: N
authors.lastname: Damann
authors.forename: Markus
authors.initials: M
authors.lastname: Rothermel
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Klupp
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.forename: Hanns
authors.initials: H
authors.lastname: Hatt
authors.forename: Christian H
authors.initials: CH
authors.lastname: Wetzel
mesh_terms: D000344:Afferent Pathways / Q000166:cytology / Q000502:physiology*; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D009296:Nasal Cavity / Q000294:innervation*; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology*; D010321:Parvoviridae / Q000502:physiology; D037121:Plant Lectins; D058913:Purinergic Agonists; D058910:Purinergic P2 Receptor Agonists; D011983:Receptors, Purinergic / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058476:Receptors, Purinergic P2X2; D012867:Skin / Q000294:innervation*; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D050052:TRPC Cation Channels / Q000819:agonists / Q000378:metabolism; D050053:TRPM Cation Channels / Q000819:agonists / Q000378:metabolism; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014276:Trigeminal Nerve / Q000166:cytology / Q000502:physiology*
chemical_list: C045475:Griffonia simplicifolia lectins; C546402:P2rx2 protein, mouse; D037121:Plant Lectins; D058913:Purinergic Agonists; D058910:Purinergic P2 Receptor Agonists; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D013779:Tetrodotoxin