Consequences of a Human TRPA1 Genetic Variant on the Perception of Nociceptive and Olfactory Stimuli

• Published in: PloS one Vol. 9; no. 4; p. e95592
• Main Authors: Schütz, Michael, Oertel, Bruno G., Heimann, Dirk, Doehring, Alexandra, Walter, Carmen, Dimova, Violeta, Geisslinger, Gerd, Lötsch, Jörn
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Adult; Alleles; Analysis; Aroma compounds; Biology and Life Sciences; Calcium Channels - genetics; Carbon dioxide; Carriers; Cold; Cold pressing; Deoxyribonucleic acid; Diabetic neuropathy; DNA; Drugs; Ecology; Electrical stimuli; Female; Gene mutations; Genetic diversity; Genetic variance; Genetic variation; Genetics; Genotype & phenotype; Haplotypes; Heat stimuli; Humans; Hydrogen sulfide; Hypotheses; Ion channels; Male; Medicine and Health Sciences; Molecular biology; Mutation; Nerve Tissue Proteins - genetics; Nociception; Odor thresholds; Odorants; Odors; Olfaction; Olfaction disorders; Olfactory discrimination; Olfactory discrimination learning; Olfactory stimuli; Olfactory thresholds; Pain; Pain - genetics; Pain perception; Pain sensitivity; Perception; Pharmacology; Phenotype; Polymorphism, Single Nucleotide - genetics; Semantics; Sensitivity; Sensory stimulation; Smell - genetics; Stimulants; Temperature perception; Transient Receptor Potential Channels - genetics; TRPA1 Cation Channel; White people; Whites; Young Adult; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095592

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. 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). 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. 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.