Mol Pain
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Congenital insensitivity to pain (OMIM 243000) is an extremely rare disorder caused by loss-of-function mutations in SCN9A encoding Nav1.7. Although the SCN9A mutations and phenotypes of painlessness and anosmia/hyposmia in patients are previously well documented, the complex relationship between genotype and phenotype of congenital insensitivity to pain remains unclear. Here, we report a congenital insensitivity to pain patient with novel SCN9A mutations. ⋯ Arg99His significantly decreased current density and reduced total Nav1.7 protein levels, whereas p. Trp917Gly almost abolished Nav1.7 sodium current without affecting its protein expression. These revealed that mutations in Nav1.7 in this congenital insensitivity to pain patient still retained partial channel function, but the patient showed completely painlessness, the unexpected genotypic-phenotypic relationship of SCN9A mutations in our patient may challenge the previous findings "Nav1.7 total loss-of-function leads to painlessness." Additionally, these findings are helpful for understanding the critical amino acid for maintaining function of Nav1.7, thus contributing to the development of Nav1.7-targeted analgesics.
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One out of seven women will develop a state of chronic postoperative pain following robot-assisted hysterectomy for endometrial cancer. Recently, metabolic studies have indicated that circulating lipids and lipoproteins could act as nociceptive modulators and thereby influence the induction and perpetuation of pain. The objectives of this explorative study were (1) to examine the preoperative serologic variations in concentrations of lipids, lipoproteins, and various low-molecular metabolites in patients with and without chronic postoperative pain after robot-assisted hysterectomy and (2) to explore if any of these serological biomarkers were predictive for development of chronic postoperative pain. ⋯ This explorative study substantiates the hypothesis that certain lipids, lipoproteins, and fatty acids are associated with chronic postoperative pain.
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An electrophysiological technique that can record nerve impulses from a single nerve fiber is indispensable for studying modality-specific sensory receptors such as low threshold mechanoreceptors, thermal receptors, and nociceptors. The teased-fiber single-unit recording technique has long been used to resolve impulses that are likely to be from a single nerve fiber. The teased-fiber single-unit recording technique involves tedious nerve separation procedures, causes nerve fiber impairment, and is not a true single-fiber recording method. ⋯ This new approach can record impulses from rapidly adapting mechanoreceptors (RA), slowly adapting type 1 mechanoreceptors (SA1), and slowly adapting type 2 mechanoreceptors (SA2) in these tissue preparations. We have also applied the pressure-clamped single-fiber recordings to record impulses on Aβ-fibers, Aδ-fibers, and C-fibers. The pressure-clamped single-fiber recording technique provides a new tool for sensory physiology and pain research.