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      Journal of Pain Research (submit here)

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      Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

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          Abstract

          Background

          Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis.

          Materials and methods

          Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70–120 m/s), and the second component originated from fibers (Type A γ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed.

          Results

          We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed.

          Conclusion

          Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

          Most cited references36

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          Epidemiology of severe sepsis

          Severe sepsis is a leading cause of death in the United States and the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Respiratory tract infections, particularly pneumonia, are the most common site of infection, and associated with the highest mortality. The type of organism causing severe sepsis is an important determinant of outcome, and gram-positive organisms as a cause of sepsis have increased in frequency over time and are now more common than gram-negative infections. Recent studies suggest that acute infections worsen pre-existing chronic diseases or result in new chronic diseases, leading to poor long-term outcomes in acute illness survivors. People of older age, male gender, black race, and preexisting chronic health conditions are particularly prone to develop severe sepsis; hence prevention strategies should be targeted at these vulnerable populations in future studies.
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            Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients.

            To determine risk factors and clinical consequences of critical illness polyneuropathy (CIP) evaluated by the impact on duration of mechanical ventilation, length of stay and mortality. Inception cohort study. Intensive care unit of a tertiary hospital. Septic patients with multiple organ dysfunction syndrome requiring mechanical ventilation and without previous history of polyneuropathy. Patients underwent two scheduled electrophysiologic studies (EPS): on the 10th and 21st days after the onset of mechanical ventilation. Eighty-two patients were enrolled, although nine of them were not analyzed. Forty-six of the 73 patients presented CIP on the first EPS and 4 other subjects were diagnosed with CIP on the second evaluation. The APACHE II scores of patients with and without CIP were similar on admission and on the day of the first EPS. However, days of mechanical ventilation [32.3 (21.1) versus 18.5 (5.8); p=0.002], length of ICU and hospital stay in patients discharged alive from the ICU as well as in-hospital mortality were greater in patients with CIP (42/50, 84% versus 13/23, 56.5%; p=0.01). After multivariate analysis, independent risk factors were hyperosmolality [odds ratio (OR) 4.8; 95% confidence intervals (95% CI) 1.05-24.38; p=0.046], parenteral nutrition (OR 5.11; 95% CI 1.14-22.88; p=0.02), use of neuromuscular blocking agents (OR 16.32; 95% CI 1.34-199; p=0.0008) and neurologic failure (GCS below 10) (OR 24.02; 95% CI 3.68-156.7; p<0.001), while patients with renal replacement therapy had a lower risk for CIP development (OR 0.02; 95% CI 0.05-0.15; p<0.001). By multivariate analysis, CIP (OR 7.11; 95% CI 1.54-32.75; p<0.007), age over 60 years (OR 9.07; 95% CI 2.02-40.68; p<0.002) and the worst renal SOFA (OR 2.18; 95% CI 1.27-3.74; p<0.002) were independent predictors of in-hospital mortality. CIP is associated with increased duration of mechanical ventilation and in-hospital mortality. Hyperosmolality, parenteral nutrition, non-depolarizing neuromuscular blockers and neurologic failure can favor CIP development.
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              The vagal innervation of the gut and immune homeostasis

              The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2018
                26 April 2018
                : 11
                : 783-790
                Affiliations
                [1 ]Department of Physiology, Federal University of Sergipe, São Cristóvão, Brazil
                [2 ]Department of Physiology, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, Brazil
                [3 ]Laboratory of Morphology and Structural Biology, Science and Technology Institute – ITP, Aracaju, Brazil
                Author notes
                Correspondence: Lúcio Ricardo Leite Diniz, Department of Physiology, Universidade Federal de Sergipe (UFS), São Cristovão, 49100-000 SE, Brazil, Tel +55 79 2105 6644, Email luciodiniz@ 123456yahoo.com.br
                Article
                jpr-11-783
                10.2147/JPR.S144220
                5927063
                d15f1f79-2312-4714-8033-255906f3a5e4
                © 2018 Diniz et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Anesthesiology & Pain management
                sepsis,sciatic nerve,vagus nerve,neuronal excitability,neuropathy,peripheral nerves

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