title: Propofol restores transient receptor potential vanilloid receptor subtype-1 sensitivity via activation of transient receptor potential ankyrin receptor subtype-1 in sensory neurons.
abstract: BACKGROUND
  Cross talk between peripheral nociceptors belonging to the transient receptor potential vanilloid receptor subtype-1 (TRPV1) and ankyrin subtype-1 (TRPA1) family has been demonstrated recently. Moreover, the intravenous anesthetic propofol has directly activates TRPA1 receptors and indirectly restores sensitivity of TRPV1 receptors in dorsal root ganglion (DRG) sensory neurons. Our objective was to determine the extent to which TRPA1 activation is involved in mediating the propofol-induced restoration of TRPV1 sensitivity.
  
  
  METHODS
  Mouse DRG neurons were isolated by enzymatic dissociation and grown for 24 h. F-11 cells were transfected with complementary DNA for both TRPV1 and TRPA1 or TRPV1 only. The intracellular Ca concentration was measured in individual cells via fluorescence microscopy. After TRPV1 desensitization with capsaicin (100 nM), cells were treated with propofol (1, 5, and 10 μM) alone or with propofol in the presence of the TRPA1 antagonist, HC-030031 (0.5 μM), or the TRPA1 agonist, allyl isothiocyanate (AITC; 100 μM); capsaicin was then reapplied.
  
  
  RESULTS
  In DRG neurons that contain both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in DRG neurons containing only TRPV1 receptors, exposure to propofol or AITC after desensitization did not restore capsaicin-induced TRPV1 sensitivity. Similarly, in F-11 cells transfected with both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in F-11 cells transfected with TRPV1 only, neither propofol nor AITC was capable of restoring TRPV1 sensitivity.
  
  
  CONCLUSIONS
  These data demonstrate that propofol restores TRPV1 sensitivity in primary DRG neurons and in cultured F-11 cells transfected with both the TRPV1 and TRPA1 receptors via a TRPA1-dependent process. Propofol's effects on sensory neurons may be clinically important and may contribute to peripheral sensitization to nociceptive stimuli in traumatized tissue.
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, Ohio 44242, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wickley
authors.forename: Sayantani
authors.initials: S
authors.lastname: Sinha
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bratz
authors.forename: Derek S
authors.initials: DS
authors.lastname: Damron
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015742:Propofol / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000187:drug effects*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002211:Capsaicin; D015742:Propofol