Animal models of congenital hypoalgesia: Untapped potential for assessing pain-related plasticity.

Over the last 20 years a large number of transgenic mouse models have been produced showing different degrees of congenital hypoalgesia; some of these models mimic known human conditions while others seemingly have no human counterpart. However, very little significant contributions to our understanding of pain neurobiology were obtained from this multitude of animal models; in most cases the study of these animals was limited to the characterization of its pain perception without addressing the long term consequences of their hypoalgesic condition. In this review we discuss the untapped potential that these animal models of congenital hypoalgesia hold for future studies addressing brain plasticity during permanent conditions of reduced pain perception, and that may result in important insights on the interplay between pain, emotion, and cognition. Revisiting hypoalgesia using modern techniques of functional neurophysiology in awake animals may complement the recent literature of functional clinical and preclinical studies that improve our understanding of the central malplasticity caused by pain.

Evaluación de los conocimientos y de la aplicación de la tetanalgesia en una unidad de neonatología / Assessment of knowledge and application of tetanalgesia in a unit of neonatology

Introducción: Durante la hospitalización, los neonatos están sometidos a constantes procedimientos dolorosos y estresantes. Está demostrado que la lactancia materna realiza un efecto analgésico. Este beneficio analgésico se conoce como tetanalgesia. Objetivo: Valorar el conocimiento de los profesionales sanitarios sobre la tetanalgesia y analizar las causas de su falta de implantación durante los procedimientos dolorosos realizados en el neonato hospitalizado. Material y Métodos: Se realizó un estudio observacional, transversal y descriptivo, mediante un cuestionario validado autocumplimentado por los profesionales sanitarios en la Unidad de Neonatología del Hospital Universitario Virgen del Rocío (Sevilla). Resultados y Conclusiones: Del total de la población estudiada, 51 profesionales sanitarios, sólo el 45% conoce el concepto de tetanalgesia lo que denota el déficit de formación al respecto. De estos, sólo el 22% lo aplica. Las causas principales de la no aplicabilidad fueron la falta de consenso de los profesionales (55,56%) y la falta de tiempo (38,89%), factores relacionados con el trabajo de equipo y con las condiciones de trabajo (AU)

Introduction: During the hospitalization, newborn children are subjected to constant painful and stressful procedures. There is evidence that breastfeeding makes an analgesic effect. This is known as Tetanalgesia. Objective: To value the knowledge of health professionals on tetanalgesia and analyze the causes of their lack of implantation during painful procedures realized to hospitalize newborn children. Material and Methods: Was realized an observational, cross-sectional and descriptive study, using a validated questionnaire auto completed by health professionals in the Unit of Neonatology of the Hospital University Virgen del Rocío (Seville). Results and Conclusions: Of the total study population (51 health professionals), only 45% knew the concept of tetanalgesia what it denotes the deficit of formation in the matter. Of these, only 22% apply it. The main causes of non-applicability were lack of consensus among the professionals (55,56%) and lack of time (38,89%),factors related to teamwork and working conditions (AU)

Comparación de los conocimientos sobre dolor infantil en 2 poblaciones de profesionales de enfermería / Comparison between 2 groups of nursing professionals on the knowledge of pediatric pain

OBJETIVO: Comparar los conocimientos sobre dolor infantil entre un grupo de profesionales de enfermería de un hospital pediátrico y otro de un hospital general. MATERIAL Y MÉTODOS: Estudio descriptivo basado en la utilización de un cuestionario validado para la valoración de los conocimientos y actitudes del personal de enfermería sobre el dolor pediátrico (Pediatric Nurses' Knowledge and Attitude Survey Regarding Pain [PNKAS]). Se distribuyó el cuestionario entre el personal de enfermería de un hospital pediátrico y de un hospital general. RESULTADOS: La puntuación obtenida en el hospital pediátrico vs. hospital general fue: media, 51,7 vs. 47,2%, intervalo de confianza 95%: 47,5-56% vs. 43,6-50,8% (p = 0,098). CONCLUSIONES: No existió una mejor puntuación en el cuestionario PNKAS en la enfermería que trabaja exclusivamente con niños que en la enfermería que trabaja con población general. Resulta necesario mejorar la formación sobre el dolor pediátrico en la enfermería que atiende al niño enfermo hospitalizado

OBJECTIVE: To compare infant pain knowledge between a group of nurses who work in a pediatric hospital and one that works in a general hospital. MATERIAL AND METHODS: Descriptive study based on the use of a validated questionnaire for assessing the knowledge and attitudes of nurses about pediatric pain (Pediatric Nurses Knowledge and Attitude Survey Regarding Pain [PNKAS]). PNKAS questionnaire was distributed to the nursing staff of a pediatric hospital and a general hospital and the results were compared. RESULTS: The average score obtained in the pediatric vs. the general hospital was: mean, 51.7% vs. 47.2%, 95% confidence interval, 47.5 to 56% vs. 43.6 to 50.8% (P = .098). CONCLUSIONS: There were no differences between the scores in the PNKAS questionnaire between nurses working exclusively with children and nurses working with general population. Training on pediatric pain needs to be improved in nurses caring for sick children

Neonatal morphine in extremely and very preterm neonates: its effect on the developing brain - a review.

OBJECTIVE: Preterm infants requiring intensive care experience a large number of stressful and painful procedures. Management of stress and pain is therefore an important issue. This review provides an overview of the research on the use of morphine and its neurodevelopmental effects on this vulnerable group of neonates. METHODS: A structural literature search of both experimental and clinical data has been done using an electronic database (PubMed), but also relevant reference lists and related articles were used. RESULTS: A total of 39 sources were considered relevant for this review to elucidate the effects of morphine on the developing brain. The results showed that both animal experimental and clinical data displayed conflicting results on the effects of neonatal morphine on neurodevelopmental outcome. However, in contrast to specific short-term neurological outcomes long-term neurodevelopmental outcome does not seem to be adversely affected by morphine. CONCLUSION: After a careful review of the literature, no definite conclusions concerning the effects of neonatal morphine on the long-term neurodevelopmental outcome in extremely premature neonates can be drawn. More prospectively designed trials should be conducted using reliable and validated pain assessment scores to evaluate effects of morphine on long-term neurodevelopmental outcome to demonstrate a beneficial or adverse effect of morphine in preterm infants.

Associations between pain conditions and borderline personality disorder symptoms: findings from the National Comorbidity Survey Replication.

OBJECTIVES: Associations between 4 forms of pain (ie, arthritis, severe/frequent headaches, chronic spinal pain, and other chronic pain) and borderline personality disorder (BPD) symptoms were investigated in the general population. METHODS: Data from part II of the National Comorbidity Survey Replication (N=5692) were used. Pain conditions were assessed with self-reports. Arthritis was assessed on a lifetime basis. For the other pain conditions, variables were created to identify those with a remitted condition and those experiencing the condition in the past year. BPD symptoms were assessed with items from the International Personality Disorder Examination Screening Questionnaire. Axis I disorders were assessed with the Composite International Diagnostic Interview. RESULTS: Multiple regression analyses adjusting for sociodemographic variables and past-year psychiatric disorders indicated that those with a history of each pain condition (either remitted or past-year) had higher levels of BPD symptoms relative to those with a lifetime absence of the condition. For each condition, follow-up analyses indicated that those experiencing the condition in the past year had higher levels of BPD symptoms than those reporting a remitted condition. After adjusting for axis I psychiatric disorders, only the difference between the remitted and past-year severe/frequent headache groups remained significant. DISCUSSION: This is the first study to demonstrate that BPD symptoms are positively associated with chronic spinal pain, severe/frequent headaches, and other chronic pain conditions in a sample representative of the general population. The findings also suggest that relationships between remitted pain conditions and BPD symptoms warrant additional study.

Effects of repetitive exposure to pain and morphine treatment on the neonatal rat brain.

BACKGROUND: Untreated exposure to pain in preterm neonates might damage the vulnerable premature brain and alter development. Pain treatment is limited because analgesic agents may also have adverse neurodevelopmental consequences in newborns. OBJECTIVE: To study the effects of neonatal pain and morphine treatment on the developing brain in a neonatal rat model. METHODS: Newborn rats were randomly assigned to: treatment with formalin injections (group 1), saline injections (group 2) and controls receiving no injections (group 3). Treatment was given on postnatal days 1-3 (model A), 1-5 (model B) and 10-12 (model C). Brains were studied histologically and protein expression was evaluated (protein kinase C epsilon and doublecortin). Effects of preemptive morphine treatment were studied in the same models (models A+M and B+M). RESULTS: Formalin injections resulted in increased apoptotic scores in models A and B. Saline injections increased the number of degenerative cells only in model B. Morphine showed protective effects in formalin-treated animals of model A+M and saline-treated animals of model B+M only. In model C, no neurodegenerative effects were detected. The protein expression of doublecortin showed a pain-related upregulation in the thalamus region, whereas protein kinase C epsilon expression was upregulated in the cortex. CONCLUSIONS: Severe inflammatory pain and pain caused by repetitive injections in neonatal rats may cause major changes in the developing brain during the first week of life. Morphine may only protect the newborn brain against these changes in specific situations.

Ethical charter of Union of European Neonatal and Perinatal Societies.

The Union of European Neonatal and Perinatal Societies, worried for the lack of unanimous guidelines in the ethical domain, propose a 10-point charter about the ethical rights of the newborns. It is complementary to other charters, such as the United Nations charter of children's rights, but it adds some specific and debated points, to find a common denominator, hopefully useful to the ongoing debate.

Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy.

BACKGROUND: Inherited erythermalgia (also termed "erythromelalgia"), characterized by episodic burning pain in the distal extremities evoked by warmth, has been causally linked with mutations of the Na(v)1.7 sodium channel, which is preferentially expressed in nociceptors. Thus far, Na(v)1.7 mutations within intracellular linker parts of the channel have been physiologically characterized. OBJECTIVE: To investigate a Na(v)1.7 erythermalgia mutation that substitutes one uncharged amino acid for another within an S4 segment. METHODS: Whole-cell patch-clamp analysis was used to study biophysical properties of wild-type and mutant (F216S) Na(v)1.7 channels in mammalian cells. RESULTS: The F216S mutation hyperpolarizes the voltage dependence of activation by 11 mV, accelerates activation, slows deactivation, and enhances the response to slow, small depolarizations. CONCLUSION: These results provide a physiologic basis for the linkage to erythermalgia of an Na(v)1.7 mutation that substitutes one uncharged residue for another within an S4 segment of the channel. These changes should increase excitability of nociceptive dorsal root ganglion neurons in which the mutant channel is present, thus contributing to pain.

Consideraciones bioéticas en el tratamiento del dolor / Bioétical considerations in the treatment of the pain

En el abordaje del dolor, al igual que en otros aspectos de toma de decisiones clínicas, cabe una aproximación de tipo ético. Empezamos revisando las dimensiones del dolor en sus distintas vertientes, los componentes que lo conforman, sus repercusiones fisiopatológicas, la prevalencia y las causas de su inadecuado control, para, a partir de ello, fundamentar el control del dolor como un derecho inherente a la dignidad de la persona humana, que en su unicidad sufre cuando experimenta el dolor. Y terminamos realizando un somero análisis ético, a la luz de los principios éticos de respeto a la persona humana, la beneficencia, la no maleficencia y la justicia.

Dermatoglyphic (fingerprint) evidence for a congenital syndrome of early onset constipation and abdominal pain.

Chronic idiopathic constipation and abdominal pain are the most common gastrointestinal symptoms but their cause is rarely determined; therefore, they usually are called functional. To determine if congenital factors play a role in these disorders, we examined dermatoglyphic (fingerprint) patterns, a congenital marker, in 155 consecutive patients with gastrointestinal complaints. Sixty-four percent of patients with constipation and abdominal pain before age 10 yr had one or more digital arches, compared with 10% of patients without constipation and abdominal pain (p less than 0.001). Seventy percent of constipated patients with arches had the onset of symptoms before age 10 yr compared with 23% of constipated patients without arches (p less than 0.001) and 14% of patients with symptoms other than constipation (p less than 0.001). Compared with an age- and sex-matched sample of patients without arches, patients with arches had a higher prevalence of constipation and abdominal pain before age 10 (p = 0.003), were more likely (p less than 0.001) to have chronic intestinal pseudoobstruction (an organic disorder), and were less likely (p = 0.013) to have irritable bowel syndrome (a functional disorder). Identification of a congenital marker, digital arches, associated with early onset constipation and abdominal pain may help to differentiate a congenital organic syndrome from functional disorders such as the irritable bowel syndrome.