Cortical activity evoked by inoculation needle prick in infants up to one-year old

Inoculation is one of the first and most common experiences of procedural pain in infancy. However, little is known about how needle puncture pain is processed by the central nervous system in children. In this study, we describe for the first time the event-related activity in the infant brain during routine inoculation using electroencephalography. Fifteen healthy term-born infants aged 1 to 2 months (n = 12) or 12 months (n = 5) were studied in an outpatient clinic. Pain behavior was scored using the Modified Behavioral Pain Scale. A distinct inoculation event-related vertex potential, consisting of 2 late negative-positive complexes, was observable in single trials after needle contact with the skin. The amplitude of both negative-positive components was significantly greater in the 12-month group. Both inoculation event-related potential amplitude and behavioral pain scores increased with age but the 2 measures were not correlated with each other. These components are the first recordings of brain activity in response to real-life needle pain in infants up to a year old. They provide new evidence of postnatal nociceptive processing and, combined with more traditional behavioral pain scores, offer a potentially more sensitive measure for testing the efficacy of analgesic protocols in this age group

Phenotyping peripheral neuropathic pain in male and female adolescents

Neuropathic pain (NeuP) can be difficult to diagnose and manage in children. Data regarding prevalence and sex-dependent differences are limited, and more detailed phenotyping is needed. This observational cohort study recruited adolescents (10-17 years) with NeuP or complex regional pain syndrome (CRPS). After pain history and NeuP questionnaires, quantitative sensory testing was performed. Individual z-score plots were calculated with body-region control measures and matched to mechanism-related sensory profiles (sensory loss, thermal hyperalgesia, and mechanical hyperalgesia). Conditioned pain modulation was assessed with pressure pain threshold and a contralateral cold conditioning stimulus, and meaningful conditioned pain modulation defined as twice the standard error of measurement. Patients and parents completed validated questionnaires for child quality of life (QoL), pain catastrophizing, and self-reported anxiety/depression. Males (n = 23) and females (n = 43) with NeuP (n = 52) or CRPS (n = 14) reported moderate–severe pain with neuropathic sensory descriptors. Mixed patterns of sensory gain/loss at pain sites were not sex-dependent. Thermal hyperalgesia was common in both NeuP and CRPS, whereas sensory loss occurred only with NeuP and in a smaller proportion than adult cohorts. Conditioned pain modulation was inhibitory in 54%, facilitatory in 14%, and nonresponders had variable cold conditioning sensitivity. Males and females reported marked impairment of QoL, increased emotional distress, and pain catastrophising. Child–parent QoL scores correlated, but catastrophizing scores were discordant when parents or adolescents reported higher anxiety/depression. NeuP in adolescents is associated with significant pain, physical impairment, and psychosocial impairment. Quantifying alterations in somatosensory profiles, descending modulation, child and parent psychological function will inform individualized therapy and stratification for future clinical trials

Nurse-led implementation of ETAT plus is associated with reduced mortality in a children's hospital in Freetown, Sierra Leone

BACKGROUND: In the wake of the Ebola virus disease (EVD) epidemic in Sierra Leone, secondary care facilities faced an increase in admissions with few members of medical staff available to assess and treat patients. This led to long waiting times in hospital outpatient departments. The study was undertaken in the outpatient department of Ola During Children’s Hospital (the tertiary paediatric hospital for Sierra Leone) in the period immediately following the EVD epidemic of 2014–2015. AIMS: This retrospective analysis of operational programme data aimed to assess whether a quality-improvement approach and task-sharing between medical and nursing staff improved the quality of triage and the timeliness of care. METHODS: All staff working in the outpatient department were offered a 4-week training course, followed by on-the-job supervision and support for 6 months. Nurses who successfully completed the course were given responsibility for the initial assessment of sick patients and for prescribing and giving initial treatment. Data were collected at three points: before intervention and at 3 and 6 months after initiation of the intervention. All children presenting to the hospital for medical attention between 0800 and 1400 Monday to Friday were included. Triage assessment by the outpatient nurse was compared to that made by a clinically experienced observer, and the time taken for each child to be triaged, assessed and given initial treatment was recorded. RESULTS:Between months 0 and 6 of the intervention, detection of emergency signs by the triage nurse improved from 30% to 100%, and detection of priority signs improved from 34% to 100%. For children presenting with emergency signs, the median time between triage and full assessment improved from 57 minutes before intervention to 17 minutes at 3 months and 5 minutes at 6 months (p < 0.0005). For the same group, median time between triage and first antibiotic or antimalarial treatment improved from 220 minutes before intervention to 40 minutes at 3 months and 18 minutes at 6 months (p = 0.006). CONCLUSION: The results indicate that, with appropriate training and support, extending the emergency assessment and treatment of sick children to nursing staff in West African hospitals may improve the accuracy of triage and the time to assessment and treatment of children presenting with signs of serious illness

Mapping cortical responses to somatosensory stimuli in human infants with simultaneous near-infrared spectroscopy and event-related potential recording

Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) have recently provided fundamental new information about how the newborn brain processes innocuous and noxious somatosensory information. However, results derived independently from these two techniques are not entirely consistent, raising questions about the relationship between hemodynamic and electrophysiological responses in the study of touch and pain processing in the newborn. To address this, we have recorded NIRS and EEG responses simultaneously for the first time in the human infant following noxious (time-locked clinically required heel lances) and innocuous tactile cutaneous stimulation in 30 newborn infants. The results show that both techniques can be used to record quantifiable and distinct innocuous and noxious evoked activity at a group level in the newborn cortex. Noxious stimulation elicits a peak hemodynamic response that is 10-fold larger than that elicited by an innocuous stimulus (HbO2: 2.0 vs 0.3 µm) and a distinct nociceptive-specific N3P3 waveform in electrophysiological recordings. However, a novel single-trial analysis revealed that hemodynamic and electrophysiological responses do not always co-occur at an individual level, although when they do (64% of noxious test occasions), they are significantly correlated in magnitude. These data show that, while hemodynamic and electrophysiological touch and pain brain activity in newborn infants are comparable in group analyses, important individual differences remain. These data indicate that integrated and multimodal brain monitoring is required to understand central touch and pain processing in the newborn

Encoding of mechanical nociception differs in the adult and infant brain

Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0-19 days (n = 18, clinically required) and adults aged 23-48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2-4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain

Nociceptive Cortical Activity Is Dissociated from Nociceptive Behavior in Newborn Human Infants under Stress.

Newborn infants display strong nociceptive behavior in response to tissue damaging stimuli, and this is accompanied by nociceptive activity generated in subcortical and cortical areas of the brain [1, 2]. In the absence of verbal report, these nociceptive responses are used as measures of pain sensation in newborn humans, as they are in animals [3, 4]. However, many infants are raised in a physiologically stressful environment, and little is known about the effect of background levels of stress upon their pain responses. In adults, acute physiological stress causes hyperalgesia [5-7], and increased background stress increases pain [8-10], but these data cannot necessarily be extrapolated to infants. Here we have simultaneously measured nociceptive behavior, brain activity, and levels of physiological stress in a sample of 56 newborn human infants aged 36-42 weeks. Salivary cortisol (hypothalamic pituitary axis), heart rate variability (sympathetic adrenal medullary system), EEG event-related potentials (nociceptive cortical activity), and facial expression (behavior) were acquired in individual infants following a clinically required heel lance. We show that infants with higher levels of stress exhibit larger amplitude cortical nociceptive responses, but this is not reflected in their behavior. Furthermore, while nociceptive behavior and cortical activity are normally correlated, this relationship is disrupted in infants with high levels of physiological stress. Brain activity evoked by noxious stimulation is therefore enhanced by stress, but this cannot be deduced from observation of pain behavior. This may be important in the prevention of adverse effects of early repetitive pain on brain development

Sensitivity and specificity of a neuropathic screening tool (Self-report Leeds Assessment of Neuropathic Symptoms and Signs, S-LANSS) in adolescents with moderate-severe chronic pain

Neuropathic screening tools improve recognition of neuropathic pain in adults. Although utilized in pediatric populations, the sensitivity, specificity and methodology of screening tool delivery have not been compared in children. We evaluated the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) in adolescents (10-18 years) referred to a tertiary pediatric pain clinic. History and examination by specialist clinicians and multidisciplinary assessment informed classification of the primary pain type. In a prospective cohort, scores were obtained at interview (S-LANSS interview; n=161, 70% female), and following substitution of self-reported signs with examination findings in the primary pain region (LANSS-examination). Secondly, we retrospectively retrieved questionnaires self-completed by adolescents at their initial clinic appointment (S-LANSS self-completed; n=456, 73% female). Thirdly, we explored relationships between patient-reported outcomes and S-LANSS scores. S-LANSS interview scores varied with pain classification, and S-LANSS self-completed scores were similarly highest with neuropathic pain (median[IQR]: 18[11,21]) and complex regional pain syndrome (21[14,24]), variable with musculoskeletal pain (13[7,19]) and lowest with visceral pain (6.5[2,11.5]) and headache (8.5[4,14]). As in adults, the cutpoint score of 12/24 was optimal. Sensitivity was highest with inclusion of examination findings and lowest with self-completion (LANSS-examination vs interview vs self-completed: 86.3% vs 80.8% vs 74.7%), but specificity was relatively low (37.8% vs 36.7% vs 48%). High S-LANSS scores in non-neuropathic groups were associated with female sex and high pain catastrophizing. The S-LANSS is a sensitive screening tool for pain with neuropathic features in adolescents, but needs to be interpreted in the context of clinical evaluation. (clinicaltrials.gov NCT03312881

Emergency Triage Assessment and Treatment Plus (ETAT+): adapting training to strengthen quality improvement and task-sharing in emergency paediatric care in Sierra Leone

BACKGROUND: Over the past 25 years Sierra Leone has made progress in reducing maternal and child mortality, but the burden of preventable paediatric deaths remains high. Further progress towards achieving the Sustainable Development Goals will require greater strengthening of the health care system, including hospital care for perinatal and paediatric conditions. Emergency Triage Assessment and Treatment Plus (ETAT+) may offer a useful tool. METHODS: The five-day ETAT+ course was adapted as a six-month programme of in-situ training and mentoring integrated with patient flow and service delivery improvements in 14 regional and district government hospitals across the country. Nurses were trained to carry out the initial resuscitation and assessment of the sick paediatric patient, and to administer the first dose of medication per protocol. The course was for all clinical staff; most participants were nurses. RESULTS: The intervention was associated with an improvement in the quality of paediatric care and a reduction in mortality. In 2017 mortality decreased by 33.1%, from 14.5% at baseline to 9.7% after six months of the intervention. Mortality at the start of the 2018 intervention was 8.5% and reduced over six months to 6.5%. Care quality indicators showed improvement across the two intervention periods, with some evidence of sustained effect. CONCLUSIONS: These results suggest that adapted ETAT+ training with in-situ mentoring alongside improved patient flow and service delivery supports improvements in the quality of paediatric care in Sierra Leonean hospitals. ETAT+ may provide an affordable framework for improving the quality of secondary paediatric care in Sierra Leone and a model of nurse-led resuscitation may allow for prompt and timely emergency paediatric care in Sierra Leonean hospitals where there are fewer physicians and other resources for care

Amygdalar Functional Connectivity Differences Associated With Reduced Pain Intensity in Pediatric Peripheral Neuropathic Pain

Background: There is evidence of altered corticolimbic circuitry in adults with chronic pain, but relatively little is known of functional brain mechanisms in adolescents with neuropathic pain (NeuP). Pediatric NeuP is etiologically and phenotypically different from NeuP in adults, highlighting the need for pediatric-focused research. The amygdala is a key limbic region with important roles in the emotional-affective dimension of pain and in pain modulation. Objective: To investigate amygdalar resting state functional connectivity (rsFC) in adolescents with NeuP. Methods This cross-sectional observational cohort study compared resting state functional MRI scans in adolescents aged 11–18 years with clinical features of chronic peripheral NeuP (n = 17), recruited from a tertiary clinic, relative to healthy adolescents (n = 17). We performed seed-to-voxel whole-brain rsFC analysis of the bilateral amygdalae. Next, we performed post hoc exploratory correlations with clinical variables to further explain rsFC differences. Results: Adolescents with NeuP had stronger negative rsFC between right amygdala and right dorsolateral prefrontal cortex (dlPFC) and stronger positive rsFC between right amygdala and left angular gyrus (AG), compared to controls (PFDR&amp;lt;0.025). Furthermore, lower pain intensity correlated with stronger negative amygdala-dlPFC rsFC in males (r = 0.67, P = 0.034, n = 10), and with stronger positive amygdala-AG rsFC in females (r = −0.90, P = 0.006, n = 7). These amygdalar rsFC differences may thus be pain inhibitory. Conclusions: Consistent with the considerable affective and cognitive factors reported in a larger cohort, there are rsFC differences in limbic pain modulatory circuits in adolescents with NeuP. Findings also highlight the need for assessing sex-dependent brain mechanisms in future studies, where possible

EEG, behavioural and physiological recordings following a painful procedure in human neonates

We present a dataset of cortical, behavioural, and physiological responses following a single, clinically required noxious stimulus in a neonatal sample. Cortical activity was recorded from 112 neonates (29-47 weeks gestational age at study) using a 20-channel electroencephalogram (EEG), which was time-locked to a heel lance. This data is linked to pain-related behaviour (facial expression), physiology (heart rate, oxygenation) and a composite clinical score (Premature Infant Pain Profile, PIPP). The dataset includes responses to non-noxious sham and auditory controls. The infants' relevant medical and pain history was collected up to the day of the study and recorded in an extensive database of variables including clinical condition at birth, diagnoses, medications, previous painful procedures, injuries, and selected maternal information. This dataset can be used to investigate the cortical, physiological, and behavioural pain-related processing in human infants and to evaluate the impact of medical conditions and experiences upon the infant response to noxious stimuli. Furthermore, it provides information on the formation of individual pain phenotypes