Central Sensitization (CS) has been proposed as a common pathophysiological mechanism to explain related syndromes for which no specific organic cause can be found. The term Central Sensitivity Syndrome (CSS) has been proposed to describe these poorly understood disorders related to CS. The goal of this investigation was to develop the Central Sensitization Inventory (CSI), which identifies key symptoms associated with CSSs, and quantifies the degree of these symptoms. The utility of the CSI, to differentiate among different types of chronic pain patients that presumably have different levels of CS impairment, was then evaluated. Study 1 demonstrated strong psychometric properties (test-retest reliability = 0.817; Cronbach's alpha = 0.879) of the CSI in a cohort of normative subjects. A factor analysis (including both normative and chronic pain subjects) yielded 4 major factors (all related to somatic and emotional symptoms), accounting for 53.4% of the variance in the dataset. In Study 2, the CSI was administered to four groups: fibromyalgia (FM); chronic widespread pain (CWP) without FM; work-related regional chronic low back pain (CLBP); and normative control group. Analyses revealed that the FM patients reported the highest CSI scores, and the normative population the lowest (p<.05). Analyses also demonstrated that the prevalence of previously diagnosed CSSs and related disorders was highest in the FM group and lowest in the normative group (p<.001). Taken together, these two studies demonstrate the psychometric strength, clinical utility, and the initial construct validity of the CSI in evaluating CS-related clinical symptoms in chronic pain populations.

p18 was first identified as a factor associated with a macromolecular tRNA synthetase complex. Here we describe the mouse p18 loss-of-function phenotype and a role for p18 in the DNA damage response. Inactivation of both p18 alleles caused embryonic lethality, while heterozygous mice showed high susceptibility to spontaneous tumors. p18 was induced and translocated to the nucleus in response to DNA damage. Expression of p18 resulted in elevated p53 levels, while p18 depletion blocked p53 induction. p18 directly interacted with ATM/ATR in response to DNA damage. The activity of ATM was dependent on the level of p18, suggesting the requirement of p18 for the activation of ATM. Low p18 expression was frequently observed in different human cancer cell lines and tissues. These results suggest that p18 is a haploinsufficient tumor suppressor and a key factor for ATM/ATR-mediated p53 activation.

The CSI is a useful and valid instrument for screening patients for the possibility of a CSS, although the chances of false positives are relatively high when evaluating patients with complex pain and psychophysiological disorders.