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To discover mechanisms of individual differences in punctate mechanosensation, we performed quantitative trait locus (QTL) mapping of the response to von Frey monofilament stimulation in BXD recombinant inbred (BXD) mice. Significant loci were detected on mouse chromosome (Chr) 5 and 15, indicating the location of underlying polymorphisms that cause heritable variation in von Frey response. Convergent evidence from public gene expression data implicates candidate genes within the loci: von Frey thresholds were strongly correlated with baseline expression of<jats:italic>Cacna2d1<\/jats:italic>,<jats:italic>Ift27<\/jats:italic>and<jats:italic>Csnk1e<\/jats:italic>in multiple brain regions of BXD strains. Systemic gabapentin and PF\u2010670462, which target the protein products of<jats:italic>Cacna2d1<\/jats:italic>and<jats:italic>Csnk1e<\/jats:italic>, respectively, significantly increased von Frey thresholds in a genotype\u2010dependent manner in progenitors and BXD strains. Real\u2010time polymerase chain reaction confirmed differential expression of<jats:italic>Cacna2d1<\/jats:italic>and<jats:italic>Csnk1e<\/jats:italic>in multiple brain regions in progenitors and showed differential expression of<jats:italic>Cacna2d1<\/jats:italic>and<jats:italic>Csnk1e<\/jats:italic>in the dorsal root ganglia of the progenitors and BXD strains grouped by QTL genotype. Thus, linkage mapping, transcript covariance and pharmacological testing suggest that genetic variation affecting<jats:italic>Cacna2d1<\/jats:italic>and<jats:italic>Csnk1e<\/jats:italic>may contribute to individual differences in von Frey filament response. This study implicates<jats:italic>Cacna2d1<\/jats:italic>and<jats:italic>Ift27<\/jats:italic>in basal mechanosensation in line with their previously suspected role in mechanical hypersensitivity.<jats:italic>Csnk1e<\/jats:italic>is implicated for von Frey response for the first time. Further investigation is warranted to identify the specific polymorphisms involved and assess the relevance of these findings to clinical conditions of disturbed mechanosensation.<\/jats:p>","DOI":"10.1111\/gbb.12302","type":"journal-article","created":{"date-parts":[[2016,5,27]],"date-time":"2016-05-27T09:47:30Z","timestamp":1464342450000},"page":"604-615","source":"Crossref","is-referenced-by-count":15,"title":["Systems genetic and pharmacological analysis identifies candidate genes underlying mechanosensation in the von Frey test"],"prefix":"10.1111","volume":"15","author":[{"given":"E. E.","family":"Young","sequence":"first","affiliation":[{"name":"Department of Anesthesiology University of Pittsburgh School of Medicine Pittsburgh PA USA"},{"name":"School of Nursing University of Connecticut Storrs CT USA"},{"name":"Institute for Systems Genomics University of Connecticut Storrs CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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