title: Consequences of a human TRPA1 genetic variant on the perception of nociceptive and olfactory stimuli.
abstract: BACKGROUND
  TRPA1 ion channels are involved in nociception and are also excited by pungent odorous substances. Based on reported associations of TRPA1 genetics with increased sensitivity to thermal pain stimuli, we therefore hypothesized that this association also exists for increased olfactory sensitivity.
  
  
  METHODS
  Olfactory function and nociception was compared between carriers (n = 38) and non-carriers (n = 43) of TRPA1 variant rs11988795 G>A, a variant known to enhance cold pain perception. Olfactory function was quantified by assessing the odor threshold, odor discrimination and odor identification, and by applying 200-ms pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and heat stimuli, and 200-ms intranasal pulses of CO2).
  
  
  RESULTS
  Among the 11 subjects with moderate hyposmia, carriers of the minor A allele (n = 2) were underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049). Moreover, carriers of the A allele discriminated odors significantly better than non-carriers (13.1±1.5 versus 12.3±1.6 correct discriminations) and indicated a higher intensity of the H2S stimuli (29.2±13.2 versus 21±12.8 mm VAS, p = 0.006), which, however, could not be excluded to have involved a trigeminal component during stimulation. Finally, the increased sensitivity to thermal pain could be reproduced.
  
  
  CONCLUSIONS
  The findings are in line with a previous association of a human TRPA1 variant with nociceptive parameters and extend the association to the perception of odorants. However, this addresses mainly those stimulants that involve a trigeminal component whereas a pure olfactory effect may remain disputable. Nevertheless, findings suggest that future TRPA1 modulating drugs may modify the perception of odorants.
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schütz
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany; Fraunhofer Institute of Molecular Biology and Applied Ecology - Project Group Translational Medcine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Oertel
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Heimann
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Doehring
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Walter
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany.
authors.forename: Violeta
authors.initials: V
authors.lastname: Dimova
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany; Fraunhofer Institute of Molecular Biology and Applied Ecology - Project Group Translational Medcine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Geisslinger
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany; Fraunhofer Institute of Molecular Biology and Applied Ecology - Project Group Translational Medcine and Pharmacology (IME-TMP), Frankfurt am Main, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
mesh_terms: D000328:Adult; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D059225:Nociception; D010146:Pain / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012660:Semantics; D012903:Smell / Q000235:genetics*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics*; D055815:Young Adult
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels
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