Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult

<p>Abstract</p> <p>Background</p> <p>Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood.</p> <p>Results</p> <p>A decrease in paw withdrawal latency (PWL) after a heat stimulus was documented in rats that received inflammatory injections in their left hind paws on postnatal day one (P1) and a reinflammation stimulus at postnatal 6-8 weeks of age, compared with normal rats. An increase in the expression of the prodynorphin (<it>proDYN</it>) gene was noted after reinflammation in the spinal cord ipsilateral to the afferents of the neonatally treated hind paw. The involvement of the activation of extracellular signal-regulated kinases (ERK) in peripheral inflammatory pain hypersensitivity was evidenced evident by the increase in phospho-ERK (pERK) activity after reinflammation.</p> <p>Conclusions</p> <p>Our results indicate that peripheral inflammation in neonates can permanently alter the pain processing pathway during the subsequent sensory stimulation of the region. Elucidation of the mechanism underlying the developing pain circuitry will provide new insights into the understanding of the early pain behaviours and the subsequent adaptation to pain.</p

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

以ct引導脊柱小面關節內注射時針刺定位及注 射體積之初步研究

腰權小面關節注射是治療小面關節症候群的常見技術，但其治療效果決定於正確可靠 的關節腔內注射。傳統的X光透視引導術需要側轉病患身體，以便利用顯影劑確定注 射針尖的位置，然而，我們在電腦斷層檢視(CT)下，發現退化的小面關節長出的骨剌 ，常常會遮蓋關節入口並阻礙注射針剌入關節。我們同時證實關節腔內注射0.5ml空 氣，比起對比顯影劑有更好的顯影效果，同時可以增加注射藥物的劑量。本實驗證實 了以CT輔助的小面關節內注射術比起傳統的X光透視引導術，可以有較優良的關節面 顯影，正確的注射針定位，可避免對比顯影劑的副作用，及較高的成功比率。 Lumbar facet joint injection has been a common technique for treatment of facet joint syndrome, but its therapeutic role depends on a reliable injection technique. In the standard fluoroscopy- guided method, an oblique placement of torso to the X-ray beam and confirmation of needle position by contrast-media arthrogram are necessary. However, we have shown that inward growth of osteophyte in degenerative facets often covered the inlet opening and obstructed the needle insertion into the capsule. We also demonstrated that small amount of air ( 0.5 ml), compared to the contrast medium, could better delineate the entire facet joint structures (joint space and capsule) under computed tomography (CT) and allowed repeated injections to the same joint for correct placement. This investigation indicated that intra-articular injection under CT guidance has the advantages over conventional fluoroscopic method in having better visualization of the articular planes, more accurate orientation of the needle pathway, the benefit of air arthrogram, and increased success rate

A Minimal Stress Model for the Assessment of Electroacupuncture Analgesia in Rats under Halothane

use of anesthetics in acupuncture analgesia is controversial . We evaluate a steady-state light anesthesia model to test whether minimal stress manipulation and reliable measurement of analgesia could be simultaneously achieved during electroacupuncture (EA) in animals. A series of experiments were performed. Firstly, EA compliance and tail- flick latencies (TFL) were compared in rats under 0.1%, 0.3%. 0.5% . 0.7%, or 1. 1% halothane for 120 min. Under 0.5% halothane , TEL were then measured in groups receiving EA at intensity of 3, 10 or 20 volt (V), I or 2 mg/kg morphine, 20 V EA plus naloxone, or control. Subsequently, the effect of EA on formalininduced hyperalgesia was tested and c-fos expression in the spinal dorsal horn was analyzed. Rats exhibited profound irritable behaviors and highly variable TFL under 0.1% or 0.3% halothane, as well as a time- dependent increase of TFL under 0.7% or 1.1% halothane . TEL remained constant at 0.5% halothane, and needle insertion and electrical stimulation were well tolerated. Under 0.5% halothane, EA increased TFI and suppressed formalin-induced hyperalgesia in an intensity -dependent and naloxone- reversible manner. EA of 20 V prolonged TFL by 74 %, suppressed formalin-induced hyperalgesia by 32.6% and decreased c-fos expression by 29.7% at the superficial and deep dorsal horn with statistically significant difference. In conclusion, 0.5% halothane provides a steady-state anesthetic level which enables the humane application of EA stimulus with the least interference on analgesic assessment . This condition serves as a minimal stress EA model in animals devoid of stress-induced analszesia while maintaining physiological and biochemical response in the experiment. (c) 2006 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved