Insomnia is one of the most common health complaints, with a high prevalence of 30~50% in the general population. In particular, neuroimaging research has revealed that widespread dysfunctions in brain regions involved in hyperarousal are strongly correlated with insomnia. However, whether the topology of the intrinsic connectivity is aberrant in insomnia remains largely unknown. In this study, resting-state functional magnetic resonance imaging (rsfMRI) in conjunction with graph theoretical analysis, was used to construct functional connectivity matrices and to extract the attribute features of the small-world networks in insomnia. We examined the alterations in global and local small-world network properties of the distributed brain regions that are predominantly implicated in the frontostriatal network between 30 healthy subjects with insomnia symptoms (IS) and 62 healthy subjects without insomnia symptoms (NIS). Correlations between the small-world properties and clinical measurements were also generated to identify the differences between the two groups. Both the IS group and the NIS group exhibited a small-worldness topology. Meanwhile, the global topological properties didn't show significant difference between the two groups. By contrast, participants in the IS group showed decreased regional degree and efficiency in the left inferior frontal gyrus (IFG) compared with subjects in the NIS group. More specifically, significantly decreased nodal efficiency in the IFG was found to be negatively associated with insomnia scores, whereas the abnormal changes in nodal betweenness centrality of the right putamen were positively correlated with insomnia scores. Our findings suggested that the aberrant topology of the salience network and frontostriatal connectivity is linked to insomnia, which can serve as an important biomarker for insomnia.

Introduction Ulinastatin, a broad-spectrum serine protease inhibitor, has been widely used to treat various diseases clinically. However, so far, the antinociceptive effect of ulinastatin remains less studied experimentally and the underlying mechanisms of ulinastatin for pain relief remain unclear. This study aimed to find evidence of the analgesic effect of ulinastatin on acute somatic and visceral pain. Methods The analgesic effect of ulinastatin on acute somatic and visceral pain was evaluated by using formalin and acetic acid-induced writhing test. The analgesic mechanism of ulinastatin was verified by detecting the peripheral inflammatory cell infiltration and spinal glial activation with hematoxylin-eosin (H&E) and immunohistochemistry staining. Results We found that both of intraperitoneal (i.p.) pre-administration and post-administration of ulinastatin could reduce the total number of flinching and the licking duration following intraplantar formalin injection in a dose-related manner. However, the inhibitory effect of ulinastatin existed only in the second phase (Phase 2) of formalin-induced spontaneous pain response, with no effect in the first phase (Phase 1). The formalin-induced edema and ulcer were also improved by i.p. administration of ulinastatin. Moreover, i.p. administration of ulinastatin was also able to delay the occurrence of acetic acid-induced writhing and reduced the total number of writhes dose-dependently. We further demonstrated that ulinastatin significantly decreased the local inflammatory cell infiltration in injured paw and peritoneum tissue under formalin and acetic acid test separately. The microglial and astrocytic activation in the spinal dorsal horn induced by intraplantar formalin and i.p. acetic acid injection were also dramatically inhibited by i.p. administration of ulinastatin. Conclusion Our results for the first time provided a new line of evidence showing that ulinastatin could attenuate acute somatic and visceral pain by inhibiting the peripheral and spinal inflammatory reaction.

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