title: Linkage between increased nociception and olfaction via a SCN9A haplotype.
abstract: OBJECTIVE
  Mutations reducing the function of Nav1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Nav1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity.
  
  
  METHODS
  SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14) or rs6746030C>T (R1150W; n = 21) were compared with non-carriers (n = 40). Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli).
  
  
  RESULTS
  The number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1), 1 allele: 10.6±2.6 (n = 34), 2 alleles: 9.5±2.1 (n = 40)). The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m(2), 1 allele: 29.8±10.4 N/m(2), 2 alleles: 33.5±10.2 N/m(2)).
  
  
  CONCLUSIONS
  The findings established a working link between nociception and olfaction via Nav1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Nav1.7 level.
authors.affiliation: Institute of Clinical Pharmacology, Goethe - University, Frankfurt am Main, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Heimann
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Hummel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Doehring
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Oertel
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000235:genetics*; D059225:Nociception / Q000502:physiology*; D010146:Pain / Q000235:genetics*; D017288:Pain Threshold / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D012903:Smell / Q000235:genetics*; D055815:Young Adult
chemical_list: D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human