Stress induces a switch of intracellular signaling in sensory neurons in a model of generalized pain.

Stress dramatically exacerbates pain in diseases such as fibromyalgia and rheumatoid arthritis, but the underlying mechanisms are unknown. We tested the hypothesis that stress causes generalized hyperalgesia by enhancing pronociceptive effects of immune mediators. Rats exposed to nonhabituating sound stress exhibited no change in mechanical nociceptive threshold, but showed a marked increase in hyperalgesia evoked by local injections of prostaglandin E(2) or epinephrine. This enhancement, which developed more than a week after exposure to stress, required concerted action of glucocorticoids and catecholamines at receptors located in the periphery on sensory afferents. The altered response to pronociceptive mediators involved a switch in coupling of their receptors from predominantly stimulatory to inhibitory G-proteins (G(s) to G(i)), and for prostaglandin E(2), emergence of novel dependence on protein kinase C epsilon. Thus, an important mechanism in generalized pain syndromes may be stress-induced coactivation of the hypothalamo-pituitary-adrenal and sympathoadrenal axes, causing a long-lasting alteration in intracellular signaling pathways, enabling normally innocuous levels of immune mediators to produce chronic hyperalgesia.

Lasting syndrome of depression produced by reduction in serotonin uptake during postnatal development: evidence from sleep, stress, and behavior.

Dysfunction of the serotonin system is implicated in sleep and emotional disorders. To test whether these impairments could arise during development, we studied the impact of early-life, transient versus genetic, permanent alterations of serotonin reuptake on sleep-wakefulness patterns, depression-related behavior, and associated physiological features. Here, we show that female mice treated neonatally with a highly selective serotonin reuptake inhibitor, escitalopram, exhibited signs of depression in the form of sleep anomalies, anhedonia, increased helplessness reversed by chronic antidepressant treatment, enhanced response to acute stress, and increased serotoninergic autoinhibitory feedback. This syndrome was not reproduced by treatment in naive adults but resembled the phenotype of mutant mice lacking the serotonin transporter, except that these exhibited decreased serotonin autoreceptor sensitivity and additional anxiety-like behavior. Thus, alteration of serotonin reuptake during development, whether induced by external or genetic factors, causes a depressive syndrome lasting into adulthood. Such early-life impairments might predispose individuals to sleep and/or mood disorders.

Prion protein aggresomes are poly(A)+ ribonucleoprotein complexes that induce a PKR-mediated deficient cell stress response.

In mammalian cells, cytoplasmic protein aggregates generally coalesce to form aggresomal particles. Recent studies indicate that prion-infected cells produce prion protein (PrP) aggresomes, and that such aggregates may be present in the brain of infected mice. The molecular activity of PrP aggresomes has not been fully investigated. We report that PrP aggresomes initiate a cell stress response by activating the RNA-dependent protein kinase (PKR). Activated PKR phosphorylates the translation initiation factor eIF2alpha, resulting in protein synthesis shut-off. However, other components of the stress response, including the assembly of poly(A)+ RNA-containing stress granules and the synthesis of heat shock protein 70, are repressed. In situ hybridization experiments and affinity chromatography on oligo(dT)-cellulose showed that PrP aggresomes bind poly(A)+ RNA, and are therefore poly(A)+ ribonucleoprotein complexes. These findings support a model in which PrP aggresomes send neuronal cells into untimely demise by modifying the cell stress response, and by inducing the aggregation of poly(A)+ RNA.

Involvement of hypoxia-triggered endoplasmic reticulum stress in outlet obstruction-induced apoptosis in the urinary bladder.

In bladder outlet obstruction (BOO), mechanical stress and ischemia/hypoxia are implicated in structural and functional alterations of the urinary bladder. Because mechanical stress and hypoxia may trigger endoplasmic reticulum (ER) stress, we examined involvement of ER stress in the damage of the bladder caused by BOO. An experimental model of BOO was established in rats by complete ligature of the urethra for 24 h, and bladders were subjected to northern blot analysis and assessment of apoptosis. Isolated urinary bladders and bladder-derived smooth muscle cells (BSMCs) were also exposed to mechanical strain and hypoxia and used for analyses. To examine involvement of ER stress in the damage of the bladder, the effects of a chemical chaperone 4-phenylbutyrate (4-PBA) were evaluated in vitro and in vivo. Outlet obstruction for 24 h induced expression of ER stress markers, GRP78 and CCAAT/enhancer-binding protein-homologous protein (CHOP), in the bladder. It was associated with induction of markers for mechanical stress (cyclooxygenases 2) and hypoxia (vascular endothelial growth factor and glyceraldehyde-3-phosphate dehydrogenase). When isolated bladders and BSMCs were subjected to mechanical strain, induction of GRP78 and CHOP was not observed. In contrast, when BSMCs were exposed to hypoxic stress caused by CoCl2 or thenoyltrifluoroacetone (TTFA), substantial upregulation of GRP78 and CHOP was observed, suggesting involvement of hypoxia in the induction of ER stress. In the bladder subjected to BOO, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells increased in the epithelial cells and BSMCs. Similarly, treatment with TTFA or CoCl2 induced apoptosis of BSMCs, and 4-PBA significantly attenuated ER stress and apoptosis triggered by these agents. Furthermore, in vivo administration with 4-PBA significantly reduced apoptosis in the bladder subjected to BOO. These results suggested that outlet obstruction caused ER stress via hypoxic stress in the bladder and that hypoxia-triggered ER stress may be involved in the induction of apoptosis in BOO.

Cross-sensitization and cross-tolerance between exogenous cannabinoid antinociception and endocannabinoid-mediated stress-induced analgesia.

Footshock stress induces both endocannabinoid mobilization and antinociception. The present studies investigated behavioral plasticity in cannabinoid antinociceptive mechanisms following repeated activation using the tail-flick test. A secondary objective was to ascertain whether blockade of stress antinociception by the CB(1) antagonist rimonabant could be attributed to changes in locomotor activity. The cannabinoid agonist WIN55,212-2 induced hypoactivity in the open field relative to vehicle-treated controls. By contrast, rimonabant, administered at a dose that virtually eliminated endocannabinoid-mediated stress antinociception, failed to alter locomotor behavior (i.e. time resting, ambulatory counts, distance traveled) in rats subjected to the same stressor. Rats exposed acutely to footshock were hypersensitive to the antinociceptive effects of WIN55,212-2 and Delta(9)-tetrahydrocannabinol (Delta(9)-THC). The converse was also true; acute Delta(9)-THC and WIN55,212-2 administration potentiated stress antinociception, suggesting a bidirectional sensitization between endocannabinoid-mediated stress antinociception and exogenous cannabinoid antinociception. Stress antinociception was also attenuated following chronic relative to acute treatment with WIN55,212-2 or Delta(9)-THC. Repeated exposure to footshock (3 min/day for 15 days), however, failed to attenuate antinociception induced by either footshock stress or WIN55,212-2. Our results demonstrate that endocannabinoid-mediated stress antinociception cannot be attributed to motor suppression. Our results further identify a functional plasticity of the cannabinoid system in response to repeated activation. The existence of cross-sensitization between endocannabinoid-mediated stress antinociception and exogenous cannabinoid antinociception suggests that these phenomena are mediated by a common mechanism. The observation of stress-induced hypersensitivity to effects of exogenous cannabinoids may have clinical implications for understanding marijuana abuse liability in humans.

Toll-like receptor 4 mediates chronic restraint stress-induced immune suppression.

Stress, either physical or psychological, can have a dramatic impact on the immune system. Little progress, however, has been made in understanding stress-induced immune suppression. We report here that mice subjected to chronic 12-hour daily physical restraint for two days significantly increased the expression of Toll-like receptor 4 (TLR4). Interestingly, TLR4-deficient mice are resistant to stress-induced lymphocyte reduction. In addition, restraint stress caused dramatic decrease in T help 1 (Th1) cytokine IFN-gamma and IL-2 levels but increase in Th2 cytokine IL-4 in wild type mice. Moreover, the restraint stress significantly inhibits changes of Th1 and Th2 cytokines in TLR4-deficient mice compared with the wild type mice. Therefore, stress modulates the immune system through a TLR4-dependent mechanism.

Physical exercise as adjuvant therapy for patients undergoing hematopoietic stem cell transplantation.

Even when the procedures are successful, patients experience considerable physical, psychological and psychosocial stress before, during and after hematopoietic stem cell transplantation (HSCT). Physical exercise therapy constitutes a potentially promising intervention to reduce such stress within the framework of HSCT because of its multidimensional effectiveness. Up to May 2007, fifteen published studies have examined physical exercise interventions in the context of HSCT, with no study reporting any unexpected or negative effects. The most common intervention involved isolated aerobic exercise programs and occurred during or after the transplantation process; strength training programs and combined intervention strategies are being examined more rarely. Significant benefits from the exercise interventions have been predominantly reported for physical performance, quality of life and fatigue status of the patients. Several other benefits like a faster recurrence of immune cells or reduced severity of therapy-related side effects can be estimated. Future research is needed for the purpose of evidence-based medicine/therapy to provide more rigorous examinations of these interventions, to address existing methodological problems and to identify further effect levels of physical exercise therapy in the context of HSCT.

Stressor-specific alterations in corticosterone and immune responses in mice.

Different stressors likely elicit different physiological and behavioral responses. Previously reported differences in the effects of stressors on immune function may reflect qualitatively different physiological responses to stressors; alternatively, both large and subtle differences in testing protocols and methods among laboratories may make direct comparisons among studies difficult. Here we examine the effects of chronic stressors on plasma corticosterone concentrations, leukocyte redistribution, and skin delayed-type hypersensitivity (DTH), and the effects of acute stressors on plasma corticosterone and leukocyte redistribution. The effects of several commonly used laboratory stressors including restraint, forced swim, isolation, and low ambient temperatures (4 degrees C) were examined. Exposure to each stressor elevated corticosterone concentrations, with restraint (a putative psychological stressor) evoking a significantly higher glucocorticoid response than other stressors. Chronic restraint and forced swim enhanced the DTH response compared to the handled, low temperature, or isolation conditions. Restraint, low temperature, and isolation significantly increased trafficking of lymphocytes and monocytes compared to forced swim or handling. Generally, acute restraint, low temperature, isolation, and handling increased trafficking of lymphocytes and monocytes. Considered together, our results suggest that the different stressors commonly used in psychoneuroimmunology research may not activate the physiological stress response to the same extent. The variation observed in the measured immune responses may reflect differential glucocorticoid activation, differential metabolic adjustments, or both processes in response to specific stressors.

Lipopolysaccharide does not affect acoustic startle reflex in mice.

Bacterial endotoxin (lipopolysaccharide; LPS) evokes in rodents an adaptive sickness behavior. It also produces changes in stress hormones secretion and activity of brain serotonergic and noradrenergic systems that have been implicated in stress responses, fear, and anxiety. Acoustic startle reflex (ASR) is regarded as a protective behavioral response that is enhanced in threatening situations or following an aversive event, and it can be modulated by physiological and emotional state of an animal. Effects of intraperitoneal injections of LPS on ASR, prepulse inhibition (PPI), locomotor activity in open field, and blood plasma corticosterone concentration were studied in lines of mice that display high (HA line) or low (LA line) swim stress-induced analgesia and also differ in emotional behaviors, including the magnitude of ASR. In both lines LPS produced robust sickness behavior, as evidenced by a decrease in locomotion and body weight, and an increase in corticosterone concentration. However, in neither line LPS injections affected responses to acoustic stimuli as assessed by the ASR and PPI magnitudes. The findings suggest that in sickness behavior induced by LPS the protective responses to salient environmental stimuli are not impaired. The significance of this finding for the concept of sickness behavior is discussed.

Mind-body medicine and cancer.

Mind-body medicine, grounded in a respectful, therapeutic partnership, should be a central element in the care of every person diagnosed with cancer. This article reviews some of the physiologic foundations of mind-body medicine, the introduction of mind-body approaches to cancer care in the 1970s, the specific mind-body approaches that have been used, and the evidence that supports their use. The importance of group support for enhancing the effectiveness of these approaches is discussed. Guidelines are offered for integrating mind-body approaches and perspectives in the care of people who have cancer.

Sustained elevation of serum cortisol level causes sensitization of coronary vasoconstricting responses in pigs in vivo: a possible link between stress and coronary vasospasm.

Vasospastic angina is induced by stress, for which cortisol secreted by activated hypothalamic/pituitary/adrenal axis may play an important role. However, direct evidence for this notion is still lacking. In this study, we examined whether sustained elevation of serum cortisol level sensitizes coronary vasoconstricting responses in pigs in vivo and, if so, whether Rho-kinase, which we found is a key molecule of coronary vasospasm, is involved. Oral administration of cortisol (20 mg/kg per day) increased its serum level to that seen in restraint stress in pigs. Thus, we examined coronary vasomotor responses in the following 4 groups: (1) control (without cortisol); (2) cortisol (20 mg/kg per day, p.o.) for 9 days; (3) cortisol plus RU38486 (a glucocorticoids receptor antagonist, 10 mg/kg per day, p.o.) for 9 days; and (4) cortisol for 9 days followed by 6-week withdrawal. Coronary angiography showed that intracoronary serotonin caused coronary hyperconstriction and reduction in coronary blood flow associated with ischemic ECG changes (coronary vasospasm) in only the cortisol group. All of these responses were abolished by hydroxyfasudil, a specific Rho-kinase inhibitor, in vivo. Organ chamber experiments demonstrated that serotonin concentration-dependently caused hypercontractions of coronary vascular smooth muscle associated with Rho-kinase activation (as evidenced by the enhanced phosphorylation of myosin binding subunit, a substrate of Rho-kinase) in only the cortisol group. All of these responses were again inhibited by hydroxyfasudil in vitro. These results indicate that sustained elevation of serum cortisol level sensitizes coronary vasoconstricting responses through Rho-kinase activation, suggesting the link between stress and coronary vasospasm.

Acute stress increases neuropsin mRNA expression in the mouse hippocampus through the glucocorticoid pathway.

Stress affects synaptic plasticity and may alter various types of behaviour, including anxiety or memory formation. In the present study, we examined the effects of acute stress (1 h restraint with or without tail-shock) on mRNA levels of a plasticity-related serine protease neuropsin (NP) in the hippocampus using semiquantitative RT-PCR and in situ hybridization. We found that NP mRNA expression was dramatically increased shortly after exposure to the acute restraint tail-shock stress and remained at high level for at least 24 h. The level of NP mRNA would be correlated to the elevated plasma concentration of the glucocorticoid corticosterone (CORT) and to the stress intensity. Application of CORT either onto primary cultured hippocampal neurons (5 nM) or in vivo to adrenalectomized (ADX) mice (10 mg/kg B.W., s.c.) mimicked the effect of stress and significantly elevated NP mRNA. These results suggest that the upregulation of NP mRNA after stress is CORT-dependent and point to a role for neuropsin in stress-induced neuronal plasticity.

Depth of anesthesia with desflurane does not influence the endocrine-metabolic response to pelvic surgery.

BACKGROUND: It has been reported that, with deep levels of anesthesia achieved with general anesthetic agents and opioids, post-operative consumption of morphine and pain intensity can be reduced. It is not clear whether the depth of anesthesia modifies pain intensity by influencing the endocrine-metabolic stress response. The purpose of this study was to assess the influence of a high concentration of desflurane on peri-operative plasma cortisol. METHODS: The study was prospective and observer blinded, and included 20 women scheduled for elective total abdominal hysterectomy. They were randomly divided in to two groups: a deep group (D) (n=10) and a light group (L) (n=10). Anesthesia was induced with propofol, fentanyl and rocuronium: desflurane was administered at two different concentrations according to Bispectral Index monitoring (deep, 25 and light, 50). Post-operative pain relief was achieved with patient-controlled analgesia (PCA) with intravenous morphine. Blood samples were taken before, during and after surgery for the measurement of plasma cortisol, glucose and lactate. Post-operative pain visual analog scale (VAS) and morphine consumption were recorded at regular intervals for the first 24 h. RESULTS: The Concentrations of plasma cortisol, glucose and lactate increased with surgery in both groups, and remained elevated, with no difference between the two groups. VAS and morphine consumptions were similar in both groups. CONCLUSION: The results show that there is no relationship between the intra-operative level of anesthesia depth achieved with desflurane and the extent of endocrine-metabolic stress response.

Antibodies in cold stressed mice recognize a surface protein in Toxoplasma gondii tachyzoites.

Physical or psychological stressors are known to have significant consequences for immune function and the outcome of disease in human and animal models. In mice, cold water stress (CWS) has been shown to delay control of acute infection and reactivation of latent infections. Increased levels of parasite-specific IgG and IgM antibodies are observed when CWS is applied in the chronic phase. The present study examined the effects of a physical stressor, CWS, on tachyzoites antigens of Toxoplasma gondii, with particular emphasis on a low molecular weight antigen, 5 kDa, which seems to be recognized by antibodies from mice subjected to CWS in the chronic phase. This antigen is not recognized by antibodies from infected mice not subjected to CWS. Sera obtained from stressed and infected (CWS + INF) mice subjected to CWS during the chronic phase (CWS + INF + CWS) were used to harvest anti-5-kDa antibodies for immunolocalization studies. Tachyzoite lysate preparations were electrophoretically separated and transferred to nitrocellulose membranes. Strips of nitrocellulose containing tachyzoite antigens in the 4-10-kDa range were used to select for anti-5-kDa antibodies. Harvested anti-5-kDa localized this antigen on the surface of tachyzoites. This antigen was not present in bradyzoite preparations. Treatment with phosphatidylinositol-specific phospholipase C showed this antigen was not anchored to the cell membrane through glycosyl-phosphatidylinositol. Strong antibody responses in stressed animals during the chronic phase are associated with parasite reactivation. The 5-kDa antigen constitutes a unique immunogenic component of T. gondii, with significant diagnostic potential for identifying reactivation of latent infections.

Differential effects comparing exercise and pharmacologic stress on left ventricular function using gated Tc-99m sestamibi SPECT.

OBJECTIVE: Although post-ischemic stunning has emerged as an important marker for severe coronary artery disease (CAD), differences in stress methods may have different effects on left ventricular (LV) volumes and function. METHODS: To assess differential effects comparing exercise and pharmacologic stress on the LV measurements, (99m)Tc-sestamibi gated single-photon emission computed tomography (SPECT) acquired more than 30 min after stress and at rest was evaluated in 38 patients undergoing adenosine triphosphate (ATP) stress (ATP group) and 38 age-and sex-matched patients subjected to exercise stress (Ex group) among 268 patients with normal SPECT findings. RESULTS: Coronary risk factors and LV volumetric measurements at baseline were similar in the two groups. Compared with volumetric measurements at rest, end-diastolic volume (EDV) increased (72 +/- 21 ml to 74 +/- 21 ml; P = 0.01), end-systolic volume increased (25 +/- 12 ml to 28 +/- 13 ml; P = 0.001), and ejection fraction (EF) decreased after stress (66% +/- 8% to 63% +/- 9%; P < 0.002) in the ATP group. In the Ex group, by contrast, no such change was observed. In addition, changes in EDV (3 +/- 6 vs. -1 +/- 5 ml; P = 0.01) and the stress-to-rest ratio of EDV (1.04 +/- 0.09 vs. 0.99 +/- 0.08; P < 0.02) after stress were greater in the ATP than in the Ex group. CONCLUSIONS: Differential effects of stress methods on LV volumes persist more than 30 min after the stress. These findings should be kept in mind when interpreting post-ischemic stunning.

The effects on heart rate and temperature of mice and vas deferens responses to noradrenaline when their cage mates are subjected to daily restraint stress.

Performing stressful procedures in view of cage mates may cause stress in observer animals. However, it is not known if stressful procedures performed in close proximity to, but not in view of cage mates are stressful for the (observer) cage mates. Radiotelemetry and postmortem in vitro studies of the vas deferens were used to determine the effects of stress on observers. Heart rate (HR) and core body temperature (cBT) were recorded for 1 h following weighing of a cage mate or 1 h during restraint of a cage mate and the hour following return of the restrained mouse to the cage. This procedure was repeated daily for 15 days. HR and cBT were increased in observers during both restraint and weighing of cage mates. Analysis of the area under the curve showed that HR and cBT in observers were significantly higher during restraint of a cage mate than after weighing of a cage mate. When mice were returned to the cage after weighing or restraint, HR and cBT were significantly higher in the cage mates of restrained animals. Comparison between days 1, 3, 7 and 14 found that, as the experiment progressed, HR and cBT were significantly reduced in the observer mice during the hour following return of the cage mates after restraint. Results from previous studies have shown that chronic stress causes the vas deferens to become hypersensitive to exogenous application of noradrenaline (NAd). In this study, vas deferens from observers of restraint had a significantly increased response to NAd. These results indicate that stressful procedures should be conducted in isolation from other mice.

Effect of bad collocation of wing tag on feather amelanosis, heterophil-to-lymphocyte ratio, fluctuating asymmetry, and tonic immobility duration in white-faced black spanish hens.

The purpose of the present study was to analyze the effects of bad collocation of the wing tag on feather amelanosis, the heterophil-to-lymphocyte ratio, fluctuating asymmetry, and tonic immobility duration at 140 d of age in hens from the White-Faced Black Spanish breed. A total of 52 females were used. There was a significant difference (P < 0.05) for the heterophil-to-lymphocyte ratio and the tonic immobility duration between groups of females with bad or good collocation of the wing tag, with the ratio being higher and the duration being longer in the former group. Females with bad collocation of the wing tag had significant heterophilia and lymphopenia (P < 0.05). There was a significant difference (P < 0.05) in the fluctuating asymmetry of the middle and hind toe lengths, the combined asymmetry of the 4 toes, the fluctuating asymmetry of the earlobe area, and the combined asymmetry of toe and leg lengths and earlobe and wattle areas, with the asymmetry of birds with bad collocation of the wing tag being larger than that of birds with good collocation of the wing tag. Results indicate that bad collocation of the wing tag negatively affects measures of stress, such as the heterophil-to-lymphocyte ratio, fluctuating asymmetry, and tonic immobility duration.

Appearance matters: artificial marking alters aggression and stress.

Artificial marking of animals for identification is frequently employed by researchers in the behavioral, biomedical, agricultural, and environmental sciences. The impact of artificial marking on experimental results is rarely explicitly considered despite evidence demonstrating that changes in phenotypic appearance can modify animal behavior and reproductive success. Here we present evidence that artificial marking of individuals within a social group has frequency-dependent effects on the behavior and physiology of domestic fowl (Gallus gallus domesticus). We demonstrate that when only 20 or 50% of individuals within a group were artificially marked, the marked birds received more aggression and had lesser body mass than the unmarked individuals within the same group. Furthermore, in groups in which only a small proportion of the individuals were marked, we report altered plasma epinephrine and dopamine levels in marked individuals. These effects of marking were imperceptible when all birds in a group were marked. This finding has important implications for animal research because, when only a subset of group members is artificially marked and used for data collection, the results obtained may not be representative of the population.

Epidemiology and treatment of painful procedures in neonates in intensive care units.

CONTEXT: Effective strategies to improve pain management in neonates require a clear understanding of the epidemiology and management of procedural pain. OBJECTIVE: To report epidemiological data on neonatal pain collected from a geographically defined region, based on direct bedside observation of neonates. DESIGN, SETTING, AND PATIENTS: Between September 2005 and January 2006, data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospectively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France (11.3 millions inhabitants) for the Epidemiology of Procedural Pain in Neonates (EPIPPAIN) study. MAIN OUTCOME MEASURE: Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy. RESULTS: The mean (SD) gestational age and intensive care unit stay were 33.0 (4.6) weeks and 8.4 (4.6) calendar days, respectively. Neonates experienced 60,969 first-attempt procedures, with 42,413 (69.6%) painful and 18,556 (30.4%) stressful procedures; 11,546 supplemental attempts were performed during procedures including 10,366 (89.8%) for painful and 1180 (10.2%) for stressful procedures. Each neonate experienced a median of 115 (range, 4-613) procedures during the study period and 16 (range, 0-62) procedures per day of hospitalization. Of these, each neonate experienced a median of 75 (range, 3-364) painful procedures during the study period and 10 (range, 0-51) painful procedures per day of hospitalization. Of the 42,413 painful procedures, 2.1% were performed with pharmacological-only therapy; 18.2% with nonpharmacological-only interventions, 20.8% with pharmacological, nonpharmacological, or both types of therapy; and 79.2% without specific analgesia, and 34.2% were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons. Prematurity, category of procedure, parental presence, surgery, daytime, and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia, whereas mechanical ventilation, noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia. CONCLUSION: During neonatal intensive care in the Paris region, large numbers of painful and stressful procedures were performed, the majority of which were not accompanied by analgesia.

Combat stress or hemorrhage? Evidence for a decision-assist algorithm for remote triage.

INTRODUCTION: In the setting of remote military triage, when physical access to the patient is not possible, traditional physiological measurements available to a combat medic may not differentiate between a wounded soldier and an active soldier. We tested the hypothesis that changes in high-frequency R-R interval spectral power (RRI HF) and pulse pressure (PP) would differ between progressive central hypovolemia (simulated hemorrhage) and exercise to evaluate their potential for remotely distinguishing active from bleeding soldiers. The RRI HF and PP were used because of their ability to track central hypovolemia. METHODS: There were 12 (8 female/4 male) healthy, normotensive, nonsmoking subjects (age 27 +/- 2 yr; height 169 +/- 3 cm; weight 68 +/- 5 kg) who were exposed to progressive lower body negative pressure (LBNP) and a supine cycle ergometer protocol. ECG and blood pressure were measured continuously. Exercise workloads were determined by matching the heart rate (HR) responses to each LBNP level. Data were analyzed in time and frequency domains. RESULTS: HR increased from 67 +/- 3 bpm at rest to 101 +/- 4 bpm by -60 mmHg LBNP and was matched within 5% during exercise. By the final stage, RRI HF decreased by a similar magnitude during both LBNP (-78 +/- 7%) and exercise (-85 +/- 6%). PP decreased by 30 +/- 4% with LBNP compared with an increase of 20 +/- 6% during exercise. CONCLUSION: Monitoring PP in combination with RRI HF would distinguish a bleeding from an active soldier. Technologies that incorporate telemetry to track these derived vital signs would provide a combat medic with remote decision support to assess soldier status on the battlefield.