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BACKGROUND: War and violence have a serious negative impact on the wellbeing and mental health of many children. Caregivers play an important role in mitigating or exacerbating this impact. OBJECTIVE: This study evaluates the impact of the nine session Caregiver Support Intervention on improving children's wellbeing and examines putative mediators of changes in children's psychosocial wellbeing. PARTICIPANTS AND SETTING: 240 female caregivers were randomly allocated (1:1) to the CSI or a waitlist control comparison condition. The study was implemented in Lebanon, in an area characterized by high levels of poverty and a high number of the Syrian refugees. METHODS: A parallel group Randomized Controlled Trial reporting on caregiver-reported child-level wellbeing. We used a combination of the Kid- and Kiddy-KINDL (parent version) for index children ages three to 12. Putative mediators of the CSI on children's psychosocial wellbeing included harsh parenting, caregiver psychological distress, caregiver wellbeing. Measurements were conducted at baseline, post-intervention and 3-months follow-up. RESULTS: We demonstrated a statistically significant change in caregiver reported children's psychosocial wellbeing at post-intervention (Mdiff =4.39, 95 % CI = 1.12, 7.65, p < 0.01, d = 0.28) but not at follow-up (Mdiff = -0.97, 95 % CI = -4.27, 2.32, p > 0.05). The proportion of the total effect of the CSI intervention on child psychosocial wellbeing mediated by caregiver distress, caregiver wellbeing and harsh parenting was 77 %. CONCLUSION: The CSI holds potential for down-stream short-term effect on improving children's psychosocial wellbeing, beyond the previously reported positive caregiver outcomes. This effect was not sustained three months post intervention. The study confirms caregiver wellbeing and parenting support as dual pathways mediating child psychosocial wellbeing. Prospective trial registration: ISRCTN22321773.
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AIMS: When the Interagency Standing Committee (IASC) adopted the composite term mental health and psychosocial support (MHPSS) and published its guidelines for MHPSS in emergency settings in 2007, it aimed to build consensus and strengthen coordination among relevant humanitarian actors. The term MHPSS offered an inclusive tent by welcoming the different terminologies, explanatory models and intervention methods of diverse actors across several humanitarian sectors (e.g., health, protection, education, nutrition). Since its introduction, the term has become well-established within the global humanitarian system. However, it has also been critiqued for papering over substantive differences in the intervention priorities and conceptual frameworks that inform the wide range of interventions described as MHPSS. Our aims are to clarify those conceptual frameworks, to argue for their essential complementarity and to illustrate the perils of failing to adequately consider the causal models and theories of change that underlie our interventions. METHODS: We describe the historical backdrop against which the term MHPSS and the IASC guidelines were developed, as well as their impact on improving relations and coordination among different aid sectors. We consider the conceptual fuzziness in the field of MHPSS and the lack of clear articulation of the different conceptual frameworks that guide interventions. We describe the explanatory models and intervention approaches of two primary frameworks within MHPSS, which we label clinical and social-environmental. Using the examples of intimate partner violence and compromised parenting in humanitarian settings, we illustrate the complementarity of these two frameworks, as well as the challenges that can arise when either framework is inappropriately applied. RESULTS: Clinical interventions prioritise the role of intrapersonal variables, biological and/or psychological, as mediators of change in the treatment of distress. Social-environmental interventions emphasise the role of social determinants of distress and target factors in the social and material environments in order to lower distress and increase resilience in the face of adversity. Both approaches play a critical role in humanitarian settings; however, the rationale for adopting one or the other approach is commonly insufficiently articulated and should be based on a thorough assessment of causal processes at multiple levels of the social ecology. CONCLUSIONS: Greater attention to the 'why' of our intervention choices and more explicit articulation of the causal models and theories of change that underlie those decisions (i.e., the 'how'), may strengthen intervention effects and minimise the risk of applying the inappropriate framework and actions to a particular problem.
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Altruismo , Conflictos Armados , Salud Mental , Sistemas de Apoyo Psicosocial , Medio Social , Humanos , RefugiadosRESUMEN
The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H2 ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second.
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BACKGROUND: Gastric emptying is a complex physiological process regulating the division of a meal into smaller partitions for the small intestine. Disrupted gastric emptying contributes to digestive disease, yet current measures may not reflect different mechanisms by which the process can be altered. METHODS: We have developed high temporal resolution solid and liquid gastric emptying breath tests in mice using [13 C]-octanoic acid and off axis- integrated cavity output spectroscopy (OA-ICOS). Stretched gamma variate and 2-component stretched gamma variate models fit measured breath excretion data. KEY RESULTS: These assays detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or physiological (nutrients, cold exposure stress, diabetes) manipulations and remain stable over time. High temporal resolution resolved complex excretion curves with 2 components, which was more prevalent in mice with delayed gastric emptying following streptozotocin-induced diabetes. There were differences in the gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a greater occurrence of two-phase gastric emptying curves in the latter strain. Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but with no effect on the occurrence of two-phase gastric emptying curves. A greater proportion of two-phase gastric emptying was induced in Balb/c mice with the administration of PYY (8-80 nmol) 60 min following meal ingestion. CONCLUSIONS AND INFERENCES: Collectively, these results demonstrate the utility of high temporal resolution gastric emptying assays. Two-phase gastric emptying is more prevalent than previously reported, likely involves intestinal feedback, but contributes little to the overall rate of gastric emptying.
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Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena-both in isolation and in interaction-to explore emergent cellular-level features under physiological and pathological conditions.
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Early research on the mental health of civilians displaced by armed conflict focused primarily on the direct effects of exposure to war-related violence and loss. Largely overlooked in this war exposure model were the powerful effects of ongoing stressors related to the experience of displacement itself. An ecological model of refugee distress is proposed, drawing on research demonstrating that mental health among refugees and asylum seekers stems not only from prior war exposure, but also from a host of ongoing stressors in their social ecology, or displacement-related stressors. Implications of this model for addressing the mental health and psychosocial needs of refugees and other displaced populations are considered.
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Conflictos Armados/psicología , Salud Mental , Refugiados/psicología , Trastornos por Estrés Postraumático/psicología , Estrés Psicológico/psicología , Violencia/psicología , Guerra , Adaptación Psicológica , Adulto , Femenino , Humanos , Acontecimientos que Cambian la Vida , Masculino , Medio Social , Exposición a la GuerraRESUMEN
The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C2 to C4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles. KEY POINTS: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.
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H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.
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Exobiología , Medio Ambiente Extraterrestre/química , Hidrocarburos Clorados/análisis , Marte , Compuestos Orgánicos Volátiles/análisis , Bahías , Dióxido de Carbono/análisis , Dióxido de Carbono/química , Sedimentos Geológicos/análisis , Sedimentos Geológicos/química , Oxígeno/análisis , Oxígeno/química , Sulfuros/análisis , Sulfuros/química , Agua/análisis , Agua/químicaRESUMEN
Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity's Sample Analysis at Mars instrument suite. H2O, SO2, CO2, and O2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H2O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO2. Evolved O2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.
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OBJECTIVE: This case series examines the feasibility, specificity, and preliminary effectiveness of NeuroGame Therapy (NGT) for improving wrist control in four children with cerebral palsy (CP). NGT uses surface electromyographic (sEMG) signals routed through motivating computer games to improve motor control. METHODS: Primary outcomes of NGT included feasibility (hours of play) and specificity (changes in sEMG activity during game play). Secondary outcomes included changes in co-contraction, range of motion, segmental alignment, and spontaneous upper extremity function following intervention. RESULTS: Participants completed a mean of 8.8 hours of NGT over 5-6 weeks. Participants demonstrated dramatic improvement of the sEMG activity during game play. Several participants also showed improvements in range of motion, co-contraction, and spontaneous upper extremity function following NGT. CONCLUSION: This case series provides evidence for the feasibility, specificity, and effectiveness of NGT. Future studies will pair NGT with functional practice to improve transfer of learning to daily activities.
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Parálisis Cerebral/rehabilitación , Terapia por Ejercicio/métodos , Rango del Movimiento Articular/fisiología , Muñeca/fisiopatología , Adolescente , Parálisis Cerebral/fisiopatología , Niño , Electromiografía , Estudios de Factibilidad , Femenino , Humanos , Masculino , Proyectos de Investigación , Resultado del TratamientoRESUMEN
Nerve growth factor (NGF) antagonism has long been proposed as a chronic pain treatment. In 2010, the FDA suspended clinical trials using tanezumab, a humanized monoclonal anti-NGF antibody, to treat osteoarthritis due to worsening joint damage in 16 patients. Increased physical activity in the absence of acute pain which normally prevents self-harm was purported as a potential cause. Such an adverse effect is consistent with an extension of tanezumab's primary mechanism of action by decreasing pain sensitivity below baseline levels. In animal inflammatory pain models, NGF antagonism decreases intraepidermal nerve fiber (IENF) density and attenuates increases in expression of nociception-related proteins, such as calcitonin gene-related peptide (CGRP) and substance P (SP). Little is known of the effects of NGF antagonism in noninflamed animals and the hypoalgesia that ensues. In the current study, we immunized rats with NGF or cytochrome C (cytC) and examined (1) nocifensive behaviors with thermal latencies, mechanical thresholds, the hot plate test, and the tail flick test, (2) IENF density, and (3) expression of CGRP, SP, voltage-gated sodium channel 1.8 (Nav1.8), and glutaminase in subpopulations of dorsal root ganglion (DRG) neurons separated by size and isolectin B4 (IB4) labeling. Rats with high anti-NGF titers had delayed responses on the hot plate test but no other behavioral abnormalities. Delayed hot plate responses correlated with lower IENF density. CGRP and SP expression was decreased principally in medium (400-800 µm(2)) and small neurons (<400 µm(2)), respectively, regardless of IB4 labeling. Expression of Nav1.8 was only decreased in small and medium IB4 negative neurons. NGF immunization appears to result in a more profound antagonism of NGF than tanezumab therapy, but we hypothesize that decreases in IENF density and nociception-related protein expression are potential mechanisms for tanezumab-induced hypoalgesia.
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Inmunoglobulinas/efectos adversos , Factor de Crecimiento Nervioso/inmunología , Umbral del Dolor/fisiología , Dolor/metabolismo , Factores de Edad , Animales , Anticuerpos Monoclonales Humanizados/uso terapéutico , Péptido Relacionado con Gen de Calcitonina/metabolismo , Citocromos c/inmunología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Glicoproteínas/metabolismo , Inflamación/inducido químicamente , Inflamación/complicaciones , Masculino , Canal de Sodio Activado por Voltaje NAV1.8 , Proteínas del Tejido Nervioso/metabolismo , Dolor/tratamiento farmacológico , Dolor/etiología , Dolor/inmunología , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Canales de Sodio/metabolismo , Sustancia P/metabolismoRESUMEN
There is clear evidence to support the use of pre-operative concurrent chemo-radiotherapy (CRT) in locally advanced rectal cancer. In the UK, most patients are selected for treatment if the resection margin is predicted to be involved. The selection criteria used includes primary tumours that threaten the resection margins on high-resolution pelvic MRI and low tumours requiring abdominoperineal excision. There is no consensus, however, to guide the treatment of patients who present with advanced rectal disease and synchronous, potentially resectable, metastatic disease. This case illustrates the potential risk of omitting radiation following a good response to neoadjuvant systemic chemotherapy.
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Adenocarcinoma/terapia , Neoplasias Hepáticas/terapia , Neoplasias del Recto/terapia , Adenocarcinoma/secundario , Humanos , Neoplasias Hepáticas/secundario , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Radioterapia Adyuvante , Neoplasias del Recto/patología , Tomografía Computarizada por Rayos X , Reino UnidoRESUMEN
Evidence of relaxation has appeared, for the first time, in the extremely high-beta, steady-state field-reversed configuration plasma states driven by rotating magnetic fields (RMF) in the translation, confinement, and sustainment experiment. The plasma self-organizes into a near-force-free state in the vicinity of the magnetic axis, with significant improvement in confinement. Associated with this change in magnetic topology is the appearance of an axial RMF component; this would, in turn, generate a current drive in the poloidal direction, thus sustaining the magnetic helicity. A newly developed two-dimensional "equilibrium-lite" model is employed to analyze the magnetic properties of the final high-confinement state, and shows a large q and a significant magnetic shear in the core.
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An extremely high-beta (over 85%) self-organized field-reversed configuration (FRC) with a spherical-torus- (ST-)like core is produced in the translation, confinement, and sustainment experiment by highly super-Alfvénic translation of a spheromaklike plasmoid. Substantial flux conversion from toroidal into poloidal occurs during the capture process, resulting in the ST-like core. This plasma state exhibits a remarkable stabilizing property for the ubiquitous centrifugally driven interchange modes present in theta-pinch formed FRCs. This is explained, for the first time, by a simple model taking into account magnetic shear and centrifugal effects. The FRC-ST configuration has up to 4 times improvement in flux confinement times over the scaling of conventional theta-pinch formed FRCs and, thus, a significant improvement in the resistivity and transport.
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Information processing in the inferior colliculus depends on interactions between ascending pathways and intrinsic circuitry, both of which exist within a functional tonotopic organization. To determine how local projections of neurons in the inferior colliculus are related to tonotopy, we placed a small iontophoretic injection of biodextran amine at a physiologically characterized location in the inferior colliculus. We then used electrophysiological recording to place a grid of small deposits of Chicago Sky Blue throughout the same frequency range to specify an isofrequency contour. Using three-dimensional computer reconstructions, we analyzed patterns of transport relative to the physiologically determined isofrequency contour to quantify the extent of the intrinsic connection lamina in all three dimensions. We also performed a quantitative analysis of the numbers of cells in different regions relative to the biodextran amine injection. Biodextran amine-labeled fibers were mainly located dorsomedial to the injection site, confined within the isofrequency contour, but biodextran amine-labeled cells were mainly located ventrolateral to the injection site. When we counted numbers of labeled cells classified by morphological type, we found that both elongate and multipolar cells were labeled within the isofrequency contour. Because the dendrites of multipolar cells typically extend outside the isofrequency lamina, it is likely that they receive input from other isofrequency contours and relay it to more dorsomedial portions of their specific isofrequency contour, along with the frequency-specific projections of the elongate cells. Within a given isofrequency contour, there is a consistent organization in which intrinsic connections ascend from the ventrolateral portion to more dorsomedial points along the contour, forming a cascaded system of intrinsic feedforward connections that seem ideally suited to provide the delay lines necessary to produce several forms of selectivity for temporal patterns in inferior colliculus neurons.
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Vías Auditivas/anatomía & histología , Vías Auditivas/fisiología , Colículos Inferiores/citología , Colículos Inferiores/fisiología , Neuronas/fisiología , Estimulación Acústica/métodos , Animales , Compuestos Azo , Biotina/análogos & derivados , Mapeo Encefálico , Recuento de Células , Quirópteros/anatomía & histología , Quirópteros/fisiología , Dextranos , Relación Dosis-Respuesta en la Radiación , Potenciales Evocados Auditivos/fisiología , Potenciales Evocados Auditivos/efectos de la radiación , Imagenología Tridimensional/métodos , Neuronas/clasificación , Azul de TripanoRESUMEN
A number of studies have implicated the interactions of the excitatory amino acid L-glutamate (Glu) with its ionotropic and metabotropic receptors as important components of the mechanism underlying the dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium [MPP(+)]. Furthermore, microdialysis experiments have demonstrated that perfusion of relatively high concentrations of MPP(+) into the rat striatum evoke a delayed, massive release of Glu. Interestingly, perfusion of MPP(+) also mediates a similar release of glutathione (GSH). Together, these observations raise the possibility that the rise of extracellular Glu mediated by MPP(+) may be the result of hydrolysis of released GSH by gamma-glutamyl transpeptidase (gamma-GT). In the present investigation it is demonstrated that perfusions of solutions of 0.7 and 1.3 mM MPP(+) dissolved in artificial cerebrospinal fluid into the rat striatum evoke neurotoxic damage to dopaminergic terminals, assessed by both a two-day test/challenge procedure and tyrosine hydroxylase immunoreactivity, but without the release of Glu. Perfusions of 2.5 mM MPP(+) cause more extensive dopaminergic neurotoxicity and a dose-dependent release of Glu. However, neither this release of Glu nor MPP(+)-induced dopaminergic neurotoxicity are blocked by the irreversible gamma-GT inhibitor acivicin. Together, these observations indicate that a rise of extracellular levels of Glu is not essential for the dopaminergic neurotoxicity of MPP(+). Furthermore, the rise of extracellular Glu caused by perfusion of 2.5 mM MPP(+) is not the result of the gamma-GT-mediated hydrolysis of released GSH. It is possible that the rise of extracellular levels of Glu, L-aspartate, L-glycine and L-taurine evoked by perfusions of 2.5 mM MPP(+) into the rat striatum may reflect, at least in part, the release of these amino acids from astrocytes.
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1-Metil-4-fenilpiridinio/toxicidad , Dopaminérgicos/toxicidad , Espacio Extracelular/metabolismo , Ácido Glutámico/metabolismo , Glutatión/metabolismo , Neostriado/metabolismo , Síndromes de Neurotoxicidad/metabolismo , Aminoácidos/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Dopamina/metabolismo , Electroquímica , Inhibidores Enzimáticos/farmacología , Espacio Extracelular/efectos de los fármacos , Inmunohistoquímica , Isoxazoles/farmacología , Masculino , Microdiálisis , Neostriado/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , gamma-Glutamiltransferasa/antagonistas & inhibidores , gamma-Glutamiltransferasa/metabolismoRESUMEN
Interchange modes have been a key limiting instability for many magnetic confinement fusion configurations. In previous studies intended to deal with these ubiquitous instabilities, complex, transport enhancing, minimum-B producing coils were added to the otherwise simple linear mirror plasma. Possible solutions for returning to a simple symmetric mirror configuration, such as ponderomotive fields, are weak and difficult to apply. A new method is demonstrated here for the first time, utilizing rotating magnetic fields that are simple to apply and highly effective. A simple and easily comprehensible theory has also been developed to explain the remarkable stabilizing properties. Although this work has been performed on field reversed configurations, it should have a wide application to other confinement schemes, and could become a cornerstone for high-beta plasma stability.
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High-beta plasmoids can survive the violent dynamics of supersonic reflection off mirror structures, producing a stable high-beta field-reversed configuration (FRC). This shows both the robustness of FRCs and their tendency to assume a preferred plasma state, possibly conforming to a relaxation principle. The key observations are (1) approximate preservation of the magnetic helicity, (2) substantial conversion from toroidal to poloidal magnetic flux, (3) substantial toroidal flow, and (4) a high-beta quiescent final state. These results are from the Translation, Confinement, and Sustainment experiment where a disorganized plasmoid is injected at super-Alfvenic speed into a confinement chamber. After successive reflections from end mirrors, the plasmoid settled into a near-FRC state with high beta and low toroidal magnetic field. The flux conversion and helicity preservation are inferred by an interpretive model.
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Effective pain management in the terminally ill patient requires an understanding of pain control strategies. Ongoing assessment of pain is crucial and can be accomplished using various forms and scales. It is also important to determine if the pain is nociceptive (somatic or visceral pain) or neuropathic (continuous dysesthesias or chronic lancinating or paroxysmal pain). Nociceptive pain can usually be controlled with nonsteroidal antiinflammatory drugs or corticosteroids, whereas neuropathic pain responds to tricyclic antidepressants or anticonvulsants. Relief of breakthrough pain requires the administration of an immediate-release analgesic medication. If a significant amount of medication for breakthrough pain is already being given, the baseline dose of sustained-release analgesic medication should be increased. If pain does not respond to one analgesic medication, physicians should use an equianalgesic dose chart when changing the medication or route of administration. Opioid rotation can be used if pain can no longer be controlled on a specific regimen. The impact of unresolved psychosocial or spiritual issues on pain management may need to be addressed.
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Analgésicos no Narcóticos/uso terapéutico , Analgésicos Opioides/uso terapéutico , Manejo del Dolor , Dolor/etiología , Cuidado Terminal/métodos , Hospitales para Enfermos Terminales , Humanos , Dolor/tratamiento farmacológico , Dimensión del Dolor , Encuestas y CuestionariosRESUMEN
Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C(1)--C(2) neurons. Extracellular potentials of single C(1)--C(2) neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2) spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C(1)-C(2) superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.