Adult-Age Inflammatory Pain Experience Enhances Long-Term Pain Vigilance in Rats

Background: Previous animal studies have illustrated a modulatory effect of neonatal pain experience on subsequent painrelated behaviors. However, the relationship between chronic pain status in adulthood and future pain perception remains unclear. Methodology/Principal Findings: In the current study, we investigated the effects of inflammatory pain experience on subsequent formalin-evoked pain behaviors and fear conditioning induced by noxious stimulation in adult rats. Our results demonstrated an increase of the second but not the first phase of formalin-induced pain behaviors in animals with a history of inflammatory pain that have recovered. Similarly, rats with persistent pain experience displayed facilitated acquisition and prolonged retention of pain-related conditioning. These effects of prior pain experience on subsequent behavior were prevented by repeated morphine administration at an early stage of inflammatory pain. Conclusions/Significance: These results suggest that chronic pain diseases, if not properly and promptly treated, may have a long-lasting impact on processing and perception of environmental threats. This may increase the susceptibility of patients to subsequent pain-related disorders, even when chronic pain develops in adulthood. These data highlight th

Diagnosis and management of glutaric aciduria type I – revised recommendations

Glutaric aciduria type I (synonym, glutaric acidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases, immunizations and surgery during a finite period of brain development, or develops insidiously without clinically apparent crises. Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and L-tryptophan. This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry (acylcarnitines). Glutaric aciduria type I is included in the panel of diseases that are identified by expanded newborn screening in some countries. It has been shown that in the majority of neonatally diagnosed patients striatal injury can be prevented by combined metabolic treatment. Metabolic treatment that includes a low lysine diet, carnitine supplementation and intensified emergency treatment during acute episodes of intercurrent illness should be introduced and monitored by an experienced interdisciplinary team. However, initiation of treatment after the onset of symptoms is generally not effective in preventing permanent damage. Secondary dystonia is often difficult to treat, and the efficacy of available drugs cannot be predicted precisely in individual patients. The major aim of this revision is to re-evaluate the previous diagnostic and therapeutic recommendations for patients with this disease and incorporate new research findings into the guideline

Does a patient’s physical activity predict recovery from an episode of acute low back pain?: a prospective cohort study

Background Advice to remain active and normalisation of activity are commonly prescribed in the management of low back pain (LBP). However, no research has assessed whether objective measurements of physical activity predict outcome and recovery in acute low back pain. Method The aims of this study were to assess the predictive relationship between activity and disability at 3 months in a sub-acute LBP population. This prospective cohort study recruited 101 consenting patients with sub-acute LBP (< 6 weeks) who completed the Roland Morris Disability Questionnaire (RMDQ), the Visual Analogue Scale, and resumption of full ‘normal’ activity question (Y/N), at baseline and 3 months. Physical activity was measured for 7 days at both baseline and at 3 months with an RT3 accelerometer and a recall questionnaire. Results Observed and self-reported measures of physical activity at baseline and change in activity from baseline to 3 months were not independent predictors of RMDQ (p > 0.05) or RMDQ change (p > 0.05) over 3 months. A self-report of a return to full ‘normal’ activities was significantly associated with greater RMDQ change score at 3 months (p < 0.001). Paired t-tests found no significant change in activity levels measured with the RT3 (p = 0.57) or the recall questionnaire (p = 0.38) from baseline to 3 months. Conclusions These results question the predictive role of physical activity in LBP recovery, and the assumption that activity levels change as LBP symptoms resolve. The importance of a patient’s perception of activity limitation in recovery from acute LBP was also highlighted. Trial registration Clinical Trial Registration Number, ACTRN1260900028228

l-Arginine Metabolism Impairment in Sepsis and Diseases: Causes and Consequences

International audienceSepsis is recognized as a common cause for admission in ICUs. In general, sepsis and many diseases lead to alterations of the metabolism of amino acids (AA), among them arginine (Ventura et al. Amino Acids 39:1417–1426, 2010) more especially. Indeed, in humans, sepsis is characterized by a substantial decrease in arginine pools. This decrease of arginine concentration is usually due to a major increase of its consumption and a decrease of its endogenous production leading to the concept of “arginine deficiency” (Ventura et al. Amino Acids 39:1417–1426, 2010). Hence, in sepsis, it is generally admitted that endogenous synthesis (i.e., arginine is a non-essential amino acid) cannot meet the needs and arginine becomes a conditionally essential AA (Pribis et al. JPEN J Parenter Enteral Nutr 36:53–59, 2012). This may have important consequences. As a matter of fact, arginine is not only a component of proteins but also a molecule that can generate a number of active metabolites (Fig. 12.1): arginine may be the precursor of nitric oxide (NO, which is essential for the immune system), of ornithine (which is recognized as a polyamine precursor), or of agmatine (which is a major regulator of cell functions). Moreover, arginine is an important element in muscle energy: after reacting with glycine and methionine, it allows the formation of creatine. Finally, arginine acts as a secretagogue (such as insulin, glucagon, growth hormones, prolactin, and catecholamines) (Wu. Amino Acids 37:1–17, 2009). This could explain why the impairment of arginine homeostasis in sepsis and several diseases can contribute to pathophysiological alterations

Investigation of copy number variations on chromosome 21 detected by comparative genomic hybridization (CGH) microarray in patients with congenital anomalies

Abstract Background The clinical features of Down syndrome vary among individuals, with those most common being congenital heart disease, intellectual disability, developmental abnormity and dysmorphic features. Complex combination of Down syndrome phenotype could be produced by partially copy number variations (CNVs) on chromosome 21 as well. By comparing individual with partial CNVs of chromosome 21 with other patients of known CNVs and clinical phenotypes, we hope to provide a better understanding of the genotype-phenotype correlation of chromosome 21. Methods A total of 2768 pediatric patients sample collected at the Genetics Laboratory at Oklahoma University Health Science Center were screened using CGH Microarray for CNVs on chromosome 21. Results We report comprehensive clinical and molecular descriptions of six patients with microduplication and seven patients with microdeletion on the long arm of chromosome 21. Patients with microduplication have varied clinical features including developmental delay, microcephaly, facial dysmorphic features, pulmonary stenosis, autism, preauricular skin tag, eye pterygium, speech delay and pain insensitivity. We found that patients with microdeletion presented with developmental delay, microcephaly, intrauterine fetal demise, epilepsia partialis continua, congenital coronary anomaly and seizures. Conclusion Three patients from our study combine with four patients in public database suggests an association between 21q21.1 microduplication of CXADR gene and patients with developmental delay. One patient with 21q22.13 microdeletion of DYRK1A shows association with microcephaly and scoliosis. Our findings helped pinpoint critical genes in the genotype-phenotype association with a high resolution of 0.1 Mb and expanded the clinical features observed in patients with CNVs on the long arm of chromosome 21