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

Abstract

BackgroundTRPA1 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.MethodsOlfactory 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).ResultsAmong 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.ConclusionsThe 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.

Psychological and Genetic Predictors of Pain Tolerance

“…Single nucleotide polymorphisms (SNPs) within the following genes were evaluated: TRPA1 (rs11988795), COMT (rs4646312, rs6269), and FAAH (rs932816, rs4141964, and rs2295633). Based on previous literature, these six SNPs were considered to be most likely to have an effect on pain perception, using a cold‐pressor test . To ensure quality control of genotype data, SNP genotypes were only used in statistical models if the SNP call rate was > 95% and SNPs were within Hardy‐Weinberg equilibrium ( P > 0.05).…”

“…Based on previous literature, these six SNPs were considered to be most likely to have an effect on pain perception, using a cold-pressor test. 4,12,16 To ensure quality control of genotype data, SNP genotypes were only used in statistical models if the SNP call rate was > 95% and SNPs were within Hardy-Weinberg equilibrium (P > 0.05).…”

“…[4][5][6][7][8][9][10][11] Genes containing associated variants include the transient receptor potential A subtype 1 gene (TRPA1), the catecholo-methyltransferase gene (COMT), and the fatty acid amide hydrolase gene (FAAH). 4,6,[12][13][14][15] TRPA1 is an ion channel that belongs to a family of transient receptor potential channels, which respond to various sensory stimuli such as pain, and the variant rs11988795 G>A in TRPA1 is known to enhance cold pain perception. 12,16 COMT is an enzyme involved in catecholamine metabolism, influencing concentrations of dopamine and norepinephrine in the brain and affecting mood…”

“…4,6,[12][13][14][15] TRPA1 is an ion channel that belongs to a family of transient receptor potential channels, which respond to various sensory stimuli such as pain, and the variant rs11988795 G>A in TRPA1 is known to enhance cold pain perception. 12,16 COMT is an enzyme involved in catecholamine metabolism, influencing concentrations of dopamine and norepinephrine in the brain and affecting mood…”

Transient receptor potential ankyrin 1 (TRPA1) antagonists

“…Obviously, these safety concerns can be mitigated by site-specific administration protocols (e.g., topical TRPA1 antagonist creams for itch). A less dangerous (but potentially not less annoying) side effect of TRPA1 antagonists may be an altered perception of odors [133]. Though not strictly an environmental irritant, it should be mentioned here that UV light was reported to activate melanocytes via TRPA1 to protect against sun damage [134,135].…”