Corneal afferents differentially target thalamic- and parabrachial-projecting neurons in spinal trigeminal nucleus caudalis.

Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal nucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway.

Distribution of CB1 cannabinoid receptors and their relationship with mu-opioid receptors in the rat periaqueductal gray.

The periaqueductal gray (PAG) is part of a descending pain modulatory system that, when activated, produces widespread and profound antinociception. Microinjection of either opioids or cannabinoids into the PAG elicits antinociception. Moreover, microinjection of the cannabinoid 1 (CB1) receptor agonist HU-210 into the PAG enhances the antinociceptive effect of subsequent morphine injections, indicating a direct relationship between these two systems. The objective of this study was to characterize the distribution of CB1 receptors in the dorsolateral and ventrolateral PAG in relationship to mu-opioid peptide (MOP) receptors. Immunocytochemical analysis revealed extensive and diffuse CB1 receptor labeling in the PAG, 60% of which was found in somatodendritic profiles. CB1 and MOP receptor immunolabeling were co-localized in 32% of fluorescent Nissl-stained cells that were analyzed. Eight percent (8%) of PAG neurons that were MOP receptor-immunoreactive (-ir) received CB1 receptor-ir appositions. Ultrastructural analysis confirmed the presence of CB1 receptor-ir somata, dendrites and axon terminals in the PAG. These results indicate that behavioral interactions between cannabinoids and opioids may be the result of cellular adaptations within PAG neurons co-expressing CB1 and MOP receptors.

Opioid receptor internalization contributes to dermorphin-mediated antinociception.

Microinjection of opioids into the ventrolateral periaqueductal gray (vlPAG) produces antinociception in part by binding to mu-opioid receptors (MOPrs). Although both high and low efficacy agonists produce antinociception, low efficacy agonists such as morphine produce limited MOPr internalization suggesting that MOPr internalization and signaling leading to antinociception are independent. This hypothesis was tested in awake, behaving rats using DERM-A594, a fluorescently labeled dermorphin analog, and internalization blockers. Microinjection of DERM-A594 into the vlPAG produced both antinociception and internalization of DERM-A594. Administration of the irreversible opioid receptor antagonist beta-chlornaltrexamine (beta-CNA) prior to DERM-A594 microinjection reduced both the antinociceptive effect and the number of DERM-A594 labeled cells demonstrating that both effects are opioid receptor-mediated. Pretreatment with the internalization blockers dynamin dominant-negative inhibitory peptide (dynamin-DN) and concanavalinA (ConA) attenuated both DERM-A594 internalization and antinociception. Microinjection of dynamin-DN and ConA also decreased the antinociceptive potency of the unlabeled opioid agonist dermorphin when microinjected into the vlPAG as demonstrated by rightward shifts in the dose-response curves. In contrast, administration of dynamin-DN had no effect on the antinociceptive effect of microinjecting the GABA(A) receptor antagonist bicuculline into the vlPAG. The finding that dermorphin-induced antinociception is attenuated by blocking receptor internalization indicates that key parts of opioid receptor-mediated signaling depend on internalization.

DNW--"did not wait" or "demographic needing work": a study of the profile of patients who did not wait to be seen in an Irish emergency department.

BACKGROUND: Patients who fail to wait for medical assessment in the emergency department (ED) have been referred to in the international literature as "did not wait" (DNW) or "left without being seen" (LWBS) patients or, indeed, simply as "walkouts". This is taken as a performance indicator internationally. In common with many countries, Ireland has very considerable problems in the delivery of ED care due largely to inadequate resources and the inappropriate use of EDs as holding bays for admitted patients. This is the first study of this size to profile the DNW phenomenon in Ireland. METHODS: The charts of DNW patients were identified and the DNW status was entered into the ED computer record. Data concerning age, sex, time of arrival, date of arrival, triage category and presenting complaint were recorded. RESULTS: In the study period there were 11 662 patient attendances, of whom 871 patients (7.47%) did not wait for assessment. Triage category was highly statistically significant, with those in the lowest triage category having the highest numbers not waiting to be seen (p<0.001). Those attending at night (p<0.001) and at the weekend (p = 0.03) were most likely to leave without being assessed. CONCLUSION: Failure to provide the service in a timely manner gives rise to patients leaving without receiving the medical assessment they came to obtain. This is a serious clinical problem and puts both those requiring care and those providing it at risk of adverse outcomes.

The Transit/Admission Lounge study.

In response to persistent overcrowding of Emergency Departments in Ireland, the Department of Health and Health Service Executive provided funding for "Transit Lounge" areas to be built. These lounges were to provide a location for patients to wait in beds pending the availability of a ward bed. This research was performed to assess the impact of such a lounge on the overcrowding of the Emergency Department and on patient outcomes. The time period from the opening of the Transit Lounge was compared with the same period a year earlier. The Transit Lounge delivers a comfortable place for patients to wait. It does not reduce Emergency Department overcrowding and has been associated with an increased time waiting for a ward bed. The solution to overcrowding is the creation of real capacity in the system so that ward beds are available in acute hospitals for the "unscheduled unwell".

Inflammatory pain-induced signaling events following a conditional deletion of the N-methyl-D-aspartate receptor in spinal cord dorsal horn.

The N-methyl-d-aspartate (NMDA) receptor in the spinal cord dorsal horn (SCDH) is one of the mechanisms involved in central sensitization during chronic pain. Previously, this laboratory created a spatio-temporal knockout (KO) of the N-methyl-d-aspartate receptor I (NR1) subunit in the mouse SCDH. The NR1 KO completely blocks NR1 gene and subsequent NMDA receptor expression and function in SCDH neurons. In the NR1 KO mice, the mechanical and cold allodynia induced at 24 h after complete Freund's adjuvant (CFA) was reduced. However, the protective effects of KO were transient and were not seen at 48 h after CFA. These observations suggest the presence of NMDA-independent pathways that contribute to CFA-induced pain. CFA induces the activation of several signaling cascades in the SCDH, including protein kinase C (PKC)gamma and extracellular signal-regulated kinases (ERK1/2). The phosphorylation of PKCgamma and ERK1/2 was inhibited in the SCDH of NR1 KO mice up to 48 h after CFA treatment, suggesting that these pathways are NMDA receptor-dependent. Interestingly, neuronal cyclooxygenase (COX) -2 expression and microglial p38 phosphorylation were induced in the SCDH of the NR1 KO at 48 h after CFA. Our findings provide evidence that inflammatory reactions are responsible for the recurrence of pain after NR1 KO in the SCDH.

The Boarders in the Emergency Department (BED) study.

BACKGROUND AND OBJECTIVES: In the Boarders in the Emergency Department (BED) study the impact of overcrowding due to boarders on patients' mortality and the likelihood of being diagnosed with methicillin resistant Staphylococcus aureus (MRSA) during admission was examined. With regard to efficiency, the impact of overcrowding on the time to first medical assessment for admitted patients, the number of patients leaving without being seen, and the rate of admission as a percentage of total emergency department attendances was explored. METHODS: The retrospective cohort analysis study of all emergency department admissions was performed using information accessed via the Diver Solution. The software integrated information from several databases. RESULTS: The average number of patients awaiting hospital admission in the emergency department at 09:00 was 20.4 (range 0-45). The average duration of stay in the emergency department following the decision to admit was 16.1 h (range 0-161 h). The number who did not wait (DNW) to be seen was strongly correlated with the time waiting for medical assessment, which in turn was correlated with the total number of attendances to the emergency department (p<0.001). The elderly waited longer for admission and had the highest mortality and the highest chance of being diagnosed with MRSA during their overall admission. CONCLUSION: It is wrong for patients who are sick enough to require admission to hospital to be kept in the emergency department, and the entire health system must respond to their plight.

Why are we waiting? A study of the patients' perspectives about their protracted stays in an emergency department.

The overcrowding of Emergency Departments compromises their critical function and the safety of patients and staff. This study asked the patients how the wait in overcrowded conditions impacted on them and the care they received and what they believed the reasons for the overcrowding were. A prospective questionnaire based structured interview study was performed. Over half (57.7%) of patients felt that the lack of inpatient beds and wards was the main reason that they experienced delays. An overwhelming 85.9% felt that the Health Authorities were not doing enough to address the overcrowding issue. Overcrowding of Emergency Departments has been identified as a major problem the solution is to be found in increasing the capacity of the acute hospital system according to the majority of our study population.

To lead or not to lead? Prospective controlled study of emergency nurses' provision of advanced life support team leadership.

BACKGROUND AND OBJECTIVES: In many emergency departments advanced life support (ALS) trained nurses do not assume a lead role in advanced resuscitation. This study investigated whether emergency nurses with previous ALS training provided good team leadership in a simulated cardiac arrest situation. METHODS: A prospective study was conducted at five emergency departments and one nurses' association meeting. All participants went through the same scenario. Details recorded included baseline blood pressure and pulse rate, time in post, time of ALS training, and subjective stress score (1 = hardly stressed; 10 = extremely stressed). Scoring took into account scenario understanding, rhythm recognition, time to defibrillation, appropriateness of interventions, and theoretical knowledge. RESULTS: Of 57 participants, 20 were ALS trained nurses, 19 were ALS trained emergency senior house officers (SHOs), and 18 were emergency SHOs without formal ALS training. The overall mean score for doctors without ALS training was 69.5%, compared with 72.3% for ALS trained doctors and 73.7% for ALS trained nurses. Nurses found the experience less stressful (subjective stress score 5.78/10) compared with doctors without ALS training (6.5/10). The mean time taken to defibrillate from the appearance of a shockable rhythm on the monitor by the nurses and those SHOs without ALS training was 42 and 40.8 seconds, respectively. CONCLUSION: ALS trained nurses performed as well as ALS trained and non ALS trained emergency SHOs in a simulated cardiac arrest situation and had greater awareness of the potentially reversible causes of cardiac arrest. Thus if a senior or middle grade doctor is not available to lead the resuscitation team, it may be appropriate for experienced nursing staff with ALS training to act as ALS team leaders rather than SHOs.