Although pain is a common symptom of various diseases and disorders, its contribution to disease pathogenesis is not well understood. Here we show using murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), that pain induces EAE relapse. Mechanistic analysis showed that pain induction activates a sensory-sympathetic signal followed by a chemokine-mediated accumulation of MHC class II+CD11b+ cells that showed antigen-presentation activity at specific ventral vessels in the fifth lumbar cord of EAE-recovered mice. Following this accumulation, various immune cells including pathogenic CD4+ T cells recruited in the spinal cord in a manner dependent on a local chemokine inducer in endothelial cells, resulting in EAE relapse. Our results demonstrate that a pain-mediated neural signal can be transformed into an inflammation reaction at specific vessels to induce disease relapse, thus making this signal a potential therapeutic target.DOI: http://dx.doi.org/10.7554/eLife.08733.001

The amount of cardiovascular support at the end of cardiac surgery may predict morbidity and mortality in adults.

No abstract

Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress-gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure. Resulting micro-inflammation activated new neural pathway including neurons in paraventricular-nucleus, dorsomedial-nucleus-of-hypothalamus, and also vagal neurons to cause fatal gastrointestinal failure. Suppression of the brain micro-inflammation or blockage of these neural pathways inhibited the gastrointestinal failure. These results demonstrate direct link between brain micro-inflammation and fatal gastrointestinal disease via establishment of a new neural pathway under stress. They further suggest that brain micro-inflammation around specific vessels could be switch to activate new neural pathway(s) to regulate organ homeostasis.DOI: http://dx.doi.org/10.7554/eLife.25517.001

P Pu ur rp po os se e: : In order to examine the efficacy of tracheal lidocaine (TL) for attenuation of the cardiovascular responses to endotracheal intubation (EI), we compared the cardiovascular responses to TL alone and EI with TL, with those to EI without TL.M Me et th ho od ds s: : Seventy-five patients (ASA I-II) were studied. Anesthesia was induced with fentanyl 2 µg·kg 1 iv, thiamylal 5 mg·kg 1 iv and sevoflurane 1.0% in oxygen. Vecuronium 0.12 mg·kg 1 was used to facilitate EI. In Group A (n=25), three minutes after induction, EI was performed. In Group B (n=25), three minutes after induction, the patients received TL (4% lidocaine, 4 mL). This was followed by immediate EI. In Group C (n=25), EI was performed two minutes after TL. Heart rate, arterial blood pressure and rate-pressure product (RPP) were measured from one minute before induction until five minutes after EI.R Re es su ul lt ts s: : The changes of RPP caused by TL alone in Group C (TL; +34.6 ± 29.0%, mean ± SD) were significantly (P <0

We systematically elucidated the relationship between tissue factor and TFPI in patients with sepsis, severe sepsis, and septic shock. Activation of tissue factor-dependent coagulation pathway not adequately balanced by TFPI has important roles in sustaining DIC and systemic inflammatory response syndrome, and it contributes to multiple organ dysfunction syndrome and death. High concentrations of neutrophil elastase released from activated neutrophils may explain, in part, the imbalance of tissue factor and TFPI in sepsis.

As evidence of inflammatory responses in whole-body ischemia and reperfusion, our study demonstrates neutrophil-endothelium interaction with signs of endothelial injury in patients with out-of-hospital cardiac arrest. These inflammatory changes may have an important role in post-resuscitation syndrome after human cardiac arrest.

No abstract