Positional cloning of a quantitative trait locus contributing to pain sensitivity: possible mediation by Tyrp1.

To identify novel pain-relevant genes, a set of 35 recombinant congenic strains derived from the sensitive C57BL/6 and resistant A/J strains were tested for their sensitivity to noxious heat on the radiant heat paw-withdrawal test. Nine strains were found to display differential sensitivity, and the two most extreme responders were used to generate independent secondary crosses for quantitative trait locus (QTL) mapping. From these genetic analyses, a QTL, which we call Tpnr5, was mapped to a 14-Mb interval of mouse chromosome 4 containing 39 genes. In addition to the paw-withdrawal test phenotype, Tpnr5 may be relevant to mechanical and inflammatory nociception. A series of strategies - including in silico analyses, reverse transcriptase polymerase chain reaction (RT-PCR) in multiple tissues and exonic DNA sequencing - were used to generate a list of six prioritized candidate genes. One of these, tyrosinase-related protein 1 (Tyrp1), displayed enriched expression in the dorsal root ganglia, an inactivating (C110Y) mutation in the resistant A/J strain, and a null mutant found to be more resistant to thermal nociception compared to its wild-type counterpart. Although other genes cannot be definitively ruled out, existing data are supportive of the candidacy of Tyrp1 as representing the Tpnr5 QTL. Tyrosinase-related protein 1 is the rate-limiting enzyme in the production of eumelanin, and possible relationships between eumelanin-expressing cells and thermal nociception are discussed. The positional cloning of Tpnr5 is also considered in light of the heuristic value but continuing challenges of QTL mapping in the mouse.

The sharpening of scaling instruments: I. An examination of principles.

The theory and practice of sharpening with particular emphasis upon dental scalers and periodontal curettes have been discussed in Part I of this series. Various cutting modes and edge characteristics are described together with the special requirements they present in sharpening. Different approaches to sharpening are examined. Stressed are the advantages of using powered rotary stones on the sides of the blade instead of the blade face in sharpening scalers and curettes. Part II will describe the sharpening procedure--materials and technique--used and preferred by the authors.

The sharpening of scaling instruments: II. A preferred technique.

The authors' preferred procedure for sharpening scalers and curettes is described in detail; powered rotary stones are used in grinding the sides of the blade. Selected sharpening materials are discussed and evaluated and the control and removal of edge burrs are described. A regular sharpening schedule is recommended, both to simplify sharpening and to extend the useful life of the armamentarium.