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Case, L. K.

Publications and source records attributed to Case, L. K..

2 recordsLinked to original sources

Selective Nerve Block of A- or C-Afferents Confirms Dual Role in Touch Pleasantness but Not Touch-Pain Modulation

Gentle and deep pressure are distinct types of touch that often elicit pleasant sensations and modulate pain. Although touch pleasantness has traditionally been attributed to unmyelinated C-tactile afferents, growing evidence suggests an important contribution of myelinated A-fibers. However, the relative role of A- and C-fibers in touch-evoked pleasantness and pain modulation remains unclear. To test the role of A- and C-fibers in touch pleasantness, healthy adults underwent selective peripheral nerve block of the superficial radial nerve to preferentially impair either A- or C-fiber function. Touch pleasantness of brushing (Study 1; N = 24) or deep pressure (Study 2; N = 24) and touch-induced modulation of heat pain were assessed before and after the nerve block. Both nerve blocks significantly reduced the perceived pleasantness of both gentle brushing and deep pressure, supporting a substantial contribution of myelinated A-fibers and well as unmyelinated C-fibers (presumably C-tactile fibers) to affective touch. In addition, block of A-fibers did not diminish touch-induced modulation of experimental heat pain, suggesting a particular pain-inhibiting role for C-tactile fibers. These findings supply causal evidence in healthy adults that myelinated A-fibers are highly involved in touch pleasantness-alongside C-tactile fibers-but are not involved in touch-induced pain relief.

neuroscience↗

Genetic Analysis of Bphse: a Novel Gene Complementing Resistance to Bordetella pertussis-Induced Histamine Sensitization

AO_SCPLOWBSTRACTC_SCPLOWHistamine is a bioactive amine associated with a plethora of normal and pathophysiological processes, with the latter being dependent on both genetic and environmental factors including infectious agents. Previously, we showed in mice that susceptibility to Bordetella pertussis and pertussis toxin (PTX) induced histamine sensitization (Bphs) is controlled by histamine receptor H1 (Hrh1/HRH1) alleles. Bphs susceptible and resistant alleles (Bphss/Bphsr) encode for two-conserved protein haplotypes. Given the importance of HRH1 signaling in health and disease, we sequenced Hrh1 across an extended panel of laboratory and wild-derived inbred strains and phenotyped them for Bphs. Unexpectedly, eight strains homozygous for the Bphsr allele phenotyped as Bphss, suggesting the existence of a modifying locus segregating among the strains capable of complementing Bphsr. Genetic analyses mapped this modifier locus to mouse chromosome 6; designated Bphs-enhancer (Bphse), within a functional linkage disequilibrium domain encoding multiple loci controlling responsiveness to histamine (Bphs/Hrh1 and Histh1-4). Interval-specific single-nucleotide polymorphism (SNP) based association testing across 50 laboratory and wild-derived inbred mouse strains and functional prioritization analyses resulted in the identification of candidate genes for Bphse within a [~]5.5 Mb interval (Chr6:111.0-116.4 Mb), including Atg7, Plxnd1, Tmcc1, Mkrn2, Il17re, Pparg, Lhfpl4, Vgll4, Rho and Syn2. Taken together, these results demonstrate the power of combining network-based computational methods with the evolutionarily significant diversity of wild-derived inbred mice to identify novel genetic mechanisms controlling susceptibility and resistance to histamine shock.

genetics↗