Central Sensitization (CS) is a proposed physiological phenomenon in which central nervous system neurons become hyper-excitable, resulting in hypersensitivity to both noxious and non-noxious stimuli. The term Central Sensitivity Syndrome (CSS) describes a group of medically-indistinct (or nonspecific) disorders, such as fibromyalgia, chronic fatigue, and irritable bowel, for which CS may be a common etiology. In a previous study, the Central Sensitization Inventory (CSI) was introduced as a screening instrument for clinicians to help identify patients with a CSS. It was found to have high reliability and validity (test-retest reliability = 0.82; Cronbach’s alpha = 0.88). The present study investigated a cohort of 121 patients who were referred to a multidisciplinary pain center, which specialized in the assessment and treatment of complex pain and psychophysiological disorders, including CSSs. A large percentage of patients (n = 89, 74%) met clinical criteria for one or more CSSs, and CSI scores were positively correlated with the number of diagnosed CSSs. A Receiver Operating Characteristic (ROC) analysis determined that a CSI score of 40 out of 100 best distinguished between the CSS patient group and a non-patient comparison sample (n = 129) (AUC= 0.86, Sensitivity = 81%, Specicifity = 75%). PERSPECTIVE The Central Sensitization Inventory (CSI) is a new self-report screening instrument to help identify patients with Central Sensitivity Syndromes, including fibromyalgia. The present study investigated CSI scores in a heterogeneous pain population, with a large percentage of CSSs, and a normative non-clinical sample, to determine a clinically-relevant cutoff value.

The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an important role in the development of breast carcinomas. This orphan receptor is efficiently downregulated by the unusual co-repressor SHP and has been thought to be ligand-independent. We present the crystal structure at a resolution of 1.9 A of the ligand-binding domain of hLRH-1 in complex with the NR box 1 motif of human SHP, which we find contacts the AF-2 region of hLRH-1 using selective structural motifs. Electron density indicates phospholipid bound within the ligand-binding pocket, which we confirm using mass spectrometry of solvent-extracted samples. We further show that pocket mutations reduce phospholipid binding and receptor activity in vivo. Our results indicate that hLRH-1's control of gene expression is mediated by phospholipid binding, and establish hLRH-1 as a novel target for compounds designed to slow breast cancer development.

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The small heterodimer partner (SHP; NROB2), a member of the nuclear receptor superfamily, contributes to the biological regulation of several major functions of the liver. However, the role of SHP in cellular proliferation and tumorigenesis has not been investigated before. Here we report that SHP negatively regulates tumorigenesis both in vivo and in vitro. SHP−/− mice aged 12 to 15 months old developed spontaneous hepatocellular carcinoma, which was found to be strongly associated with enhanced hepatocyte proliferation and increased cyclin D1 expression. In contrast, overexpressing SHP in hepatocytes of SHP-transgenic mice reversed this effect. Embryonic fibroblasts lacking SHP showed enhanced proliferation and produced increased cyclin D1 messenger RNA and protein, and SHP was shown to be a direct negative regulator of cyclin D1 gene transcription. The immortal SHP−/− fibroblasts displayed characteristics of malignant transformed cells and formed tumors in nude mice. Conclusion These results provide first evidence that SHP plays tumor suppressor function by negatively regulating cellular growth.

This finding suggests that most anti-LGI1 encephalitis develops in a population with specific HLA subtypes, providing insight into a novel disease mechanism. Ann Neurol 2017;81:183-192.