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Painful invasive procedures are often performed on newborns admitted to intensive care units (ICU). The acute and long-term effects caused by these stimuli can be investigated in animal models, such as newborn rats. Previous studies have shown that animals subjected to nociceptive stimuli in the neonatal period show sex-specific behavioral changes such as signs of anxiety or depression. Under the same conditions, neonatal stimuli also provoke an increase in the rate of neurogenesis and cell activation in the hippocampal dentate gyrus. So, this study aims to identify the possible roles of central monoamines, receptor expression (5-HT 1A), and signaling factors (p-CREB) underlying the long-term effects of neonatal nociceptive stimulation. For this, noxious stimulation was induced by intra-plantar injection of Complete Freund´s adjuvant (CFA) on the postnatal day 1 (P1) or 8 (P8). Control animals were not stimulated. On P75 the behavioral tests were conducted (hotplate and elevated plus maze), followed by sacrifice and molecular studies. Our results showed that neonatal nociceptive stimulation alters pain sensitization specially in females, while stimulation on P1 increases pain threshold, P8-stimulated animals respond with reduced pain threshold (P < 0.001). Hippocampal expression of 5-HT 1A receptor and p-CREB were reduced in P8 F group (P < 0.001) in opposition to the increased utilization rate of dopamine and serotonin in this group (P < 0.05). This study shows sex- and age-specific responses of signaling pathways within the hippocampus accompanied by altered behavioral repertoire, at long-term after neonatal painful stimulation. [ABSTRACT FROM AUTHOR]

Giuseppe De Bernardo,1 Marina Riccitelli,2 Desiree Sordino,1 Maurizio Giordano,3 Sabrina Piccolo,1 Giuseppe Buonocore,2 Serafina Perrone2 1Department of Emergency, NICU, AORN Santobono-Pausilipon, Naples, Italy; 2Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy; 3Faculty of Medicine, Federico II University, Naples, Italy Objective: To test the hypothesis that oral administration of 24% sucrose associated with ­nonnutritive sucking in healthy newborns receiving venipuncture beyond the first week of life controls pain and pain-related variation in heart rate (HR) and noninvasive oxygen saturation (SpO2).Methods: A total of 66 term newborns were enrolled between February and September 2017 in the Neonatology Department of AORN Santobono-Pausilipon, Naples. They were randomly assigned to receive oral 1 mL 24% sucrose (treated group [TG], n=33; gestational age 38.53±1.49 weeks; body weight 3,035±55 g; age 22.40±6.82 weeks) or oral 1 mL 10% glucose (control group [CG], n=33; gestational age 38.91±1.45 weeks; body weight 3,203±65 g; age 23.36±7.02 weeks) 1 minute before and during venipuncture. Evaluations were carried out between 8 and 9 am in all newborns. The Neonatal Infant Pain Scale (NIPS) was used to assess pain in newborns. Outcome measurements (HR, SpO2) were obtained before (T0), during (T1), and 1 minute after (T2) venipuncture using a Nellcor bedside SpO2 patient-monitoring system. NIPS scores were recorded throughout the procedure. Statistical analysis was performed using SPSS version 20.0. Changes in HR and SpO2 were assessed by mixed ANOVA for repeated measures. NIPS scores were evaluated by Mann–Whitney U test.Results: There were no statistically significant differences in HR or SpO2 between TG and CG at T0. HR was significantly lower in TG than CG at both T1 and T2 (P

Background: Accurate neonatal pain assessment (NPA) is the key to neonatal pain management, yet it is a challenging task for medical staff. This study aimed to analyze the clinical practicability of the artificial intelligence based NPA (AI-NPA) tool for real-world blood sampling. Method: We performed a prospective study to analyze the consistency of the NPA results given by a self-developed automated NPA system and nurses’ on-site NPAs (OS-NPAs) for 232 newborns during blood sampling in neonatal wards, where the neonatal infant pain scale (NIPS) was used for evaluation. Spearman correlation analysis and the degree of agreement of the pain score and pain grade derived by the NIPS were applied for statistical analysis. Results: Taking the OS-NPA results as the gold standard, the accuracies of the NIPS pain score and pain grade given by the automated NPA system were 88.79% and 95.25%, with kappa values of 0.92 and 0.90 (p < 0.001), respectively. Conclusion: The results of the automated NPA system for real-world neonatal blood sampling are highly consistent with the results of the OS-NPA. Considering the great advantages of automated NPA systems in repeatability, efficiency, and cost, it is worth popularizing the AI technique in NPA for precise and efficient neonatal pain management.

Neonatal pain such as that experienced by infants in the neonatal intensive care unit is known to produce later-life dysfunction including heightened pain sensitivity and anxiety, although the mechanisms remain unclear. Both chronic pain and stress in adult organisms are known to influence the corticotropin-releasing factor (CRF) system in the Central Nucleus of the Amygdala, making this system a likely candidate for changes following neonatal trauma. To examine this, neonatal rats were subjected to daily pain, non-painful handling or left undisturbed for the first week of life. Beginning on postnatal day, 24 male and female rats were subjected to a 4-day fear conditioning and sensory testing protocol. Some subjects received intra-amygdalar administration of either Vehicle, the CRF receptor 1 (CRF1) receptor antagonist Antalarmin, or the CRF receptor 2 (CRF2) receptor antagonist Astressin 2B prior to fear conditioning and somatosensory testing, while others had tissue collected following fear conditioning and CRF expression in the CeA and BLA was assessed using fluorescent in situ hybridization. CRF1 antagonism attenuated fear-induced hypersensitivity in neonatal pain and handled rats, while CRF2 antagonism produced a general antinociception. In addition, neonatal pain and handling produced a lateralized sex-dependent decrease in CRF expression, with males showing a diminished number of CRF-expressing cells in the right CeA and females showing a similar reduction in the number of CRF-expressing cells in the left BLA compared to undisturbed controls. These data show that the amygdalar CRF system is a likely target for alleviating dysfunction produced by early life trauma and that this system continues to play a major role in the lasting effects of such trauma into the juvenile stage of development.

This paper presents the first multimodal neonatal pain dataset that contains visual, vocal, and physiological responses following clinically required procedural and postoperative painful procedures. It was collected from 58 neonates (27-41 gestational age) during their hospitalization in the neonatal intensive care unit. The visual and vocal data were recorded using an inexpensive RGB camera while the physiological responses (vital signs and cortical activity) were recorded using portable bedside monitors. The recorded behavioral and physiological responses were scored by expert nurses using two validated pain scales to obtain the ground truth labels. In addition to behavioral and physiological responses, our dataset contains clinical information such as the neonate’s age, gender, weight, pharmacological and non-pharmacological interventions, and previous painful procedures. The presented multimodal dataset can be used to develop artificial intelligence systems that monitor, assess, and predict neonatal pain based on the analysis of behavioral and physiological responses. It can also be used to advance the understanding of neonatal pain, which can lead to the development of effective pain prevention and treatment.

Neonatal pain such as that experienced by infants in the neonatal intensive care unit is known to produce later-life dysfunction including heightened pain sensitivity and anxiety, although the mechanisms remain unclear. Both chronic pain and stress in adult organisms are known to influence the corticotropin-releasing factor (CRF) system in the Central Nucleus of the Amygdala, making this system a likely candidate for changes following neonatal trauma. To examine this, neonatal rats were subjected to daily pain, non-painful handling or left undisturbed for the first week of life. Beginning on postnatal day, 24 male and female rats were subjected to a 4-day fear conditioning and sensory testing protocol. Some subjects received intra-amygdalar administration of either Vehicle, the CRF receptor 1 (CRF1) receptor antagonist Antalarmin, or the CRF receptor 2 (CRF2) receptor antagonist Astressin 2B prior to fear conditioning and somatosensory testing, while others had tissue collected following fear conditioning and CRF expression in the CeA and BLA was assessed using fluorescent in situ hybridization. CRF1 antagonism attenuated fear-induced hypersensitivity in neonatal pain and handled rats, while CRF2 antagonism produced a general antinociception. In addition, neonatal pain and handling produced a lateralized sex-dependent decrease in CRF expression, with males showing a diminished number of CRF-expressing cells in the right CeA and females showing a similar reduction in the number of CRF-expressing cells in the left BLA compared to undisturbed controls. These data show that the amygdalar CRF system is a likely target for alleviating dysfunction produced by early life trauma and that this system continues to play a major role in the lasting effects of such trauma into the juvenile stage of development. [ABSTRACT FROM AUTHOR]

The current study aimed to evaluate anxiety behavior, hippocampal ionized calcium-binding adaptor molecule 1 (Iba1) and cannabinoid receptor 1 (CB1) gene expression, and nociceptive response in adulthood after a combination of fentanyl and cannabidiol (CBD) for nociceptive stimuli induced during the first week of life in rats. Complete Freund's adjuvant-induced inflammatory nociceptive insult on postnatal day (PN) 1 and PN3. Both fentanyl and CBD were used alone or in combination from PN1 to PN7. Behavioral and nociceptive tests were performed at PN60 and PN62. The expression of the microglial calcium-binding proteins Iba1 and CB1 was detected in the hippocampus using reverse Quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Our results suggest that the anxiety behavior response and immune activation in adult life depend on the CBD dose combined with fentanyl for the nociceptive stimuli induced during the first week of life. Treatment of neonatal nociceptive insult with CBD and opioids showed significant dose-dependent and male-female differences. The increased gene expression in the hippocampus of the analyzed cannabinoid gene supports this data. In addition, treatment with fentanyl led to an increase in CB1 protein expression. Moreover, the expression of Iba1 varied according to the administered dose of CBD and may or may not be associated with the opioid. A lower dose of CBD during the inflammatory period was associated with enhanced anxiety in adult life. PERSPECTIVE: The treatment of nociceptive stimuli with CBD and opioids during the first week of life demonstrated significant sex differences in adult life on anxiety behavior and supraspinal pain sensitivity., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The rising issue of opioid use during pregnancy poses an increased risk of fetal exposure to opioids in-utero and the development of neonatal abstinence syndrome (NAS). The cessation of exposure to opioids upon birth causes elevated levels of norepinephrine in the circulation enhancing sympathetic arousal. Skin conductance (SC) detects sympathetic-mediated sweating while the Neonatal Facial Coding System (NFCS) depicts facial expressions of stress and pain. We hypothesize that there will be a direct correlation between SC and NFCS scores, such that neonates with prenatal opioid exposure will have higher SC and facial responses to pain/stress as compared with healthy neonates without prenatal opioid exposure. Objective: This study evaluates the utility of SC and the NFCS in the objective assessment of early postnatal pain response in opioid-exposed and non-opioid exposed neonates. Methods: This prospective, single-center, pilot study enrolled opioid-exposed term neonates (>37 weeks) and healthy controls. Subjects were observed within 24–48 hours post-birth (and prior to opioid withdrawal) for pain at baseline, during, and post-heel lance/squeeze (HLS) with simultaneously measured SC and videotaped facial expressions. SC data included electro-dermal responses over time (EDR/second) and the average amplitude of responses (mean of peaks [MP]). Video data were scored using the NFCS by two trained coders with inter-rater agreement >85%. Results: SC and NFCS scores were significantly associated with both groups. The opioid-exposed neonates had significantly higher skin conductance indices, EDR/sec for the HLS phase, and MP for HLS and post phases as compared with controls (p <.05). Opioid-exposed neonates demonstrated higher NFCS at baseline (p =.003). Conclusions: Prenatal opioid exposure was associated with heightened sympathetic arousal during both pain and recovery phases and higher facial expressions of pain/distress at baseline only. A multimodal system of assessment may be useful in understanding the complexity and severity of opioid withdrawal associated with NAS. [ABSTRACT FROM AUTHOR]

Background: Neonatal male circumcision is a painful skin-breaking procedure that may affect infant physiological and behavioral stress responses as well as mother-infant interaction. Due to the plasticity of the developing nociceptive system, neonatal pain might carry long-term consequences on adult behavior. In this study, we examined whether infant male circumcision is associated with long-term psychological effects on adult socio-affective processing. Methods: We recruited 408 men circumcised within the first month of life and 211 non-circumcised men and measured socio-affective behaviors and stress via a battery of validated psychometric scales. Results: Early-circumcised men reported lower attachment security and lower emotional stability while no differences in empathy or trust were found. Early circumcision was also associated with stronger sexual drive and less restricted socio-sexuality along with higher perceived stress and sensation seeking. Limitations: This is a cross-sectional study relying on self-reported measures from a US population. Conclusions: Our findings resonate with the existing literature suggesting links between altered emotional processing in circumcised men and neonatal stress. Consistent with longitudinal studies on infant attachment, early circumcision might have an impact on adult socio-affective traits or behavior.

One of the most essential components of end-of-life (EOL) care for neonates is assessing and addressing distressing symptoms. There is limited evidence to guide neonatal EOL symptom management and therefore significant variety in treatment (1–4). EOL neonatal palliative care should include identifying and relieving distressing symptoms. Symptoms to manage at neonatal EOL may include pain using both non-pharmacologic and pharmacologic comfort measures, respiratory distress, secretions, agitation and neurologic symptoms, nutrition and gastrointestinal distress, and skin care. Also of equal importance is communication surrounding familial existential distress and psychosocial care (1, 5–7). Institutions should implement a guideline for neonatal EOL care as guidelines have been shown to decrease variability of interventions and increase use of pharmacologic symptom management (4). Providers should consult with palliative care teams if available for added multidisciplinary support for family and staff, which has been shown to enhance EOL care in neonates (8, 9).

Introduction: Newborns are subject to many painful procedures. Pharmacological and non-pharmacological approaches alone are not enough, and it is necessary to consider other contributing elements such as the environment, interprofessional collaboration and parental involvement. The aim of this feasibility study was to explore interprofessionality and the role of parents in improving the management of painful procedures in newborns and pain management strategies.Materials and Methods: a pre-post feasibility study using a mixed method approach was conducted. Questionnaires, interviews and focus groups were used to describe the parents' views on their child's pain management and involvement in care as well as to explore the level of interprofessionality and feasibility.Results: Collaboration between physicians and nurses improved following the implementation of a complex interprofessional intervention involving professionals, parents and newborns. In spite of improving professional collaboration in procedural pain management, parents were attributed a passive role or only marginally involved in in the infant's pain management. However, parents stated—as elicited by the questionnaires and interviews—that they wished to receive more information and be included in painful procedures executed on their infant.Discussion: Management of painful procedures in neonates needs to be changed. Interprofessional collaboration contributes to improved procedural pain management in neonates. It is essential to include parents as active members in the interprofessional healthcare team.

Modern health care has brought our society innumerable benefits but has also introduced the experience of pain very early in life. For example, it is now routine care for newborns to receive various injections or have blood drawn within 24 h of life. For infants who are sick or premature, the pain experiences inherent in the required medical care are frequent and often severe, with neonates requiring intensive care admission encountering approximately fourteen painful procedures daily in the hospital. Given that much of the world has seen a steady increase in preterm births for the last several decades, an ever-growing number of babies experience multiple painful events before even leaving the hospital. These noxious events occur during a critical period of neurodevelopment when the nervous system is very vulnerable due to immaturity and neuroplasticity. Here, we provide a narrative review of the literature pertaining to the idea that early life pain has significant long-term effects on neurosensory, cognition, behavior, pain processing, and health outcomes that persist into childhood and even adulthood. We refer to clinical and pre-clinical studies investigating how early life pain impacts acute pain later in life, focusing on animal model correlates that have been used to better understand this relationship. Current knowledge around the proposed underlying mechanisms responsible for the long-lasting consequences of neonatal pain, its neurobiological and behavioral effects, and its influence on later pain states are discussed. We conclude by highlighting that another important consequence of early life pain may be the impact it has on later chronic pain states—an area of research that has received little attention.

Introduction: Hospitalized infants undergo a lot of painful procedures during care and treatment, and the use of non-pharmacological methods to reduce the effects of pain helps the infants to relax and stay healthy. Therefore, this study aimed to determine the effect of massage by the mother on the pain of term infants after care measures. Materials and methods: This quasi-experimental study was performed on 80 infants in the neonatal ward. Neonates were selected by random sampling and randomly divided into two groups. In both groups, the pain score was measured in the first time of the invasive procedure and then in the experimental group after 5 days of massage and the control group without massage, again in the next time of the invasive procedure, the pain score was measured before, during and after the intervention. Findings obtained from the NIPS questionnaire were analyzed using SPSS statistical software. Results: The difference between the pain scores before the intervention was not significant in the control and experimental groups, but after five days of massage, the pain score in the experimental group was significantly lower than the control group. The results show that pain in children increases during and after the procedure, but the amount of pain decreases with massage by mothers. Conclusion: Clinical and therapeutic measures in the intensive care unit cause neonatal pain and massage is one of the cost-free and simple solutions to reduce pain in infants. According to the findings of our study on the positive effect of massage by the mother on neonatal pain, it is recommended that nurses use it as an effective intervention in reducing the pain of infants. [ABSTRACT FROM AUTHOR]

Background: Premature neonates receive a large number of painful procedures during their stay in the neonatal intensive care unit (NICU). However, there are many other processes that happen in the NICU, which may not be considered painful but can cause discomfort and/or stress to the neonate. Method: Pain profile during routine procedures in NICU was assessed using the premature infant pain profile (PIPP) score. Neonates of gestational age >26 weeks, less than 7 days old and admitted for less than 7 days in the NICU were included. Results: A total of 662 procedures were observed in 132 (78 M, 54 F) neonates. The mean (SD) age of the neonates was 2.4 (1.8) days and the mean (SD) birth weight was 2.3 (0.6) kg. 63 (54.5%) were of low birth weight (LBW), 85 (64.39%) were full term. High PIPP score was noted in blood sampling, heel prick, suction, and weight measurement. Significant differences were observed in the PIPP score during blood sampling and suction across gender. Some ordinary and non-stressful procedures also scored very high on the PIPP scale. Conclusions: The validity of PIPP needs to be reexamined. Our understanding of pain during routine procedures may need to be revisited. [ABSTRACT FROM AUTHOR]

Background: Neonates admitted to neonatal intensive care units experience an average of 8-17 moderate to severe painful procedures per day. Because neonates lack the cognitive capacity to express their pain's location or severity, they are very dependent on healthcare providers to recognize, assess, and manage their pain. The health and development of newborns are negatively impacted by persistent or untreated pain experienced early in life. Therefore, studying neonatal pain management practices and associated factors in healthcare is critical to tackling workforce problems, enhancing neonatal care, and lowering the long-term health impacts of neonates., Method: From January 1 to 30, 2023, a facility-based cross-sectional study design was used at six public hospitals in the Somali region of Ethiopia. A total of 336 healthcare providers enrolled using a simple random sample technique. A self-administered, structured questionnaire was utilized to collect the data. The analyses used bivariate and multivariate logistic regression. To find the association between the outcome and predictor factors, the odd ratio and the 95% CI were computed., Result: The study revealed that 35.4% [95% CI 30.4%-40.5%] of respondents reported that they had good neonatal pain management practices. Ever having undergone training in neonatal pain assessment and management [AOR = 2.26 (95% CI 1.259, 4.07)], availability of pain assessment tools [AOR = 3.05 (95% CI 1.249, 7.469)], and having a favorable attitude toward neonatal pain management practice [AOR = 3.71 (95% CI 1.525, 9.035)] were found to be factors with a significant association with neonatal pain management practice., Conclusion: Based on the study's findings, there is a low level of neonatal pain management practice among healthcare providers in the Somali region. The study emphasizes the significance of having access to pain assessment tools and the requirement for healthcare professionals to get training on neonatal pain assessment and management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Abebe, Orcho, Chane, Mesfin and Seifu.)

• Neonatal repetitive pain in rats did not change maternal behavior. • Neonatal repetitive pain did not affect basal thresholds to mechanical stimuli. • Male and female offspring had a reduction in mechanical threshold after CFA challenge. • Female animals showed higher formalin-induced hypersensitivity compared to males. Newborn infants are vulnerable to procedural stress and pain exposure on the first weeks of life that represents a critical period for the development of nociceptive, sensory, emotional, and social functions. We evaluated the nociceptive behavior of adult male and female rats that were submitted to nociceptive experience in the neonatal period and the maternal behavior in the postnatal period. The animals were submitted to repetitive needle pricking from the second to the fifteenth postnatal day (PND 2–15). Maternal behavior and litter weight were evaluated during this period. Mechanical sensitivity to pain was assessed in offsprings during the adulthood by exposing them to inflammatory stimuli, including formalin test or the Freund's complete adjuvant (CFA) injection followed by the electronic von Frey test at 0, 3, 6 and 24 h later. Maternal behavior and litter weight were not altered by pinprick stimuli during PND 2–15. Additionally, pinprick stimulation reduced the paw withdrawal threshold in CFA-injected animals compared to control. In the formalin test, there was a difference between the genders. Female rats are statically more sensitive to formalin stimulation and showed an increased licking time in both the first and second phases and increased number of flinches in second phase. Experiencing early life repetitive pain exposure increased inflammatory pain sensitivity in adult offspring rats and female rats are more sensitive to chemical stimulation. Future investigations of the mechanisms involved in this effect may contribute to the improvement of the understanding of inflammatory pain sensitivity differences. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to test the hypothesis that neonatal hip examination causes pain in newborns. Pain assessment using instruments such as the Premature Infant Pain Profile‐Revised (PIPP‐R) scale is recommended, but recently physiological and neurophysiological measures, for example, near‐infrared spectroscopy (NIRS) and galvanic skin response (GSR), have been used as well. Methods: Heart auscultation and hip examination were performed, and the response of the newborn was registered by NIRS optodes, GSR electrodes, and a pulse oximeter probe attached to the infant. The face of the newborn was filmed. Heart auscultation was used as a nonpainful reference. Results: The pain scores for hip examination were higher than for the heart auscultation. Near‐infrared spectroscopy showed a significant higher increase from baseline in oxygenated hemoglobin (HbO2) on both sides of the cortex at hip examination compared with at heart auscultation (P = .011 and P = .017). Mean PIPP‐R scores for the hip examination compared with heart auscultation increased from 3.0 to 8.1 (P = .000). The GSR analyses of hip examination compared with heart auscultation showed a significant increase in area under small peaks during the hip examination (P = .016), however, not when measured in peaks per second (P = .104). Interrater reliability was calculated for the NIRS interpretations, with an intraclass correlation coefficient (ICC) range of 0.93‐1.0 (P = .000). Discussion: Pain in newborns can have negative consequences, and pain prevention and treatment are therefore important. We conclude that neonatal hip examinations are painful and that the pain should be treated, for example, with oral sweet solution. This is a change from present routines during neonatal hip examination and is hoped to lead to a change in national guidelines. [ABSTRACT FROM AUTHOR]

Background: Pain during painful procedures in neonates has far reaching consequences. In developed countries many non-pharmacological interventions are used for neonatal pain reduction. Breast feeding has been proved to be an effective analgesic during mild to moderate painful procedures in neonates. Methods: The study, randomized controlled trial was conducted in CMH, Quetta. The study period extended from June to November 2015. Neonates included in the experimental group were breastfeed during BCG vaccination and neonates in the control group were provided with routine care. Duration of cry with needle insertion was recorded with a digital stopwatch till the baby is silent for more than 5 seconds. Results: The mean crying duration in experimental group was significantly less than control group. In experimental group mean crying duration was 16.48s (12.76) whereas in control group mean crying duration was 34.93 s(45.26). Statistically significant difference was observed between the mean crying times of the two groups (p<0.05). Conclusion: Mean duration of crying with breastfeeding is shorter than without breast feeding during BCG immunization. Breast feeding reduces pain during minor painful procedures in neonates. [ABSTRACT FROM AUTHOR]

Purpose: The rising issue of opioid use during pregnancy poses an increased risk of fetal exposure to opioids in-utero and the development of neonatal abstinence syndrome (NAS). The cessation of exposure to opioids upon birth causes elevated levels of norepinephrine in the circulation enhancing sympathetic arousal. Skin conductance (SC) detects sympathetic-mediated sweating while the Neonatal Facial Coding System (NFCS) depicts facial expressions of stress and pain. We hypothesize that there will be a direct correlation between SC and NFCS scores, such that neonates with prenatal opioid exposure will have higher SC and facial responses to pain/stress as compared with healthy neonates without prenatal opioid exposure.Objective: This study evaluates the utility of SC and the NFCS in the objective assessment of early postnatal pain response in opioid-exposed and non-opioid exposed neonates.Methods: This prospective, single-center, pilot study enrolled opioid-exposed term neonates (>37 weeks) and healthy controls. Subjects were observed within 24-48 hours post-birth (and prior to opioid withdrawal) for pain at baseline, during, and post-heel lance/squeeze (HLS) with simultaneously measured SC and videotaped facial expressions. SC data included electro-dermal responses over time (EDR/second) and the average amplitude of responses (mean of peaks [MP]). Video data were scored using the NFCS by two trained coders with inter-rater agreement >85%.Results: SC and NFCS scores were significantly associated with both groups. The opioid-exposed neonates had significantly higher skin conductance indices, EDR/sec for the HLS phase, and MP for HLS and post phases as compared with controls (p < .05). Opioid-exposed neonates demonstrated higher NFCS at baseline (p = .003).Conclusions: Prenatal opioid exposure was associated with heightened sympathetic arousal during both pain and recovery phases and higher facial expressions of pain/distress at baseline only. A multimodal system of assessment may be useful in understanding the complexity and severity of opioid withdrawal associated with NAS. [ABSTRACT FROM AUTHOR]

Aim: This review informed pain control guidelines for clinicians performing mechanical ventilation, nasal continuous positive airway pressure and endotracheal intubation on term and preterm newborn infants.Methods: We reviewed literature published between 1986 and June 2017 on analgesia and sedation during assisted ventilation and before endotracheal intubation in newborn infants admitted to neonatal intensive care units. The subsequent guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation approach.Results: Our review produced five strong standard of care recommendations. One, reduce neonatal stress and use nonpharmacological analgesia during invasive ventilation. Two, favour intermittent boluses of opioids, administered after pain scores and before invasive procedures, during short expected periods of mechanical ventilation, mainly in preterm infants affected by respiratory distress syndrome. Three, do not use morphine infusion in preterm infants under 27 gestational weeks. Four, always use algometric scores to titrate analgesic drugs doses. Five, use premedication before endotracheal intubation for a more rapid, less painful, less traumatic and safer manoeuvre. We also developed 30 conditional recommendations on therapeutic options.Conclusion: Our review produced 35 recommendations on standard care and therapeutic options relating to the analgesia and sedation of newborn infants during ventilation and before endotracheal intubation. [ABSTRACT FROM AUTHOR]

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This study investigates the effects of repetitive pinprick stimulation on preterm offspring and its impact on nociceptive responses and inflammatory hypersensitivity in adulthood. The objective is to shed light on the potential long-term consequences of neonatal pain and prematurity on sensory processing. Term and preterm rats were subjected to repetitive pinprick (PP) stimulation or control (CC) during the neonatal period. Adult rats received CFA injection to induce inflammatory hypersensitivity, and mechanical hypersensitivity was measured. Gender differences in inflammatory hypersensitivity were also examined. Maternal behavior, litter weight, and offspring growth were monitored to assess any potential influences of the stimulation on these parameters. In preterm rats, the PP stimulation did not affect baseline thresholds to mechanical stimuli, but increased mechanical hypersensitivity after CFA injection in adult rats. Females exhibited greater inflammatory hypersensitivity compared to males. Maternal behavior, litter weight, and offspring growth were not influenced by the stimulation. PP stimulation during the neonatal period led to changes in nociceptive responses in adulthood, potentially altering sensory processing. PP stimulation in preterm rats during the neonatal period resulted in changes in nociceptive responses in adulthood, leading to increased inflammatory hypersensitivity. The study emphasizes how early development can significantly impact sensory processing and further highlights the potential long-term consequences of prematurity and neonatal pain on this processing. [ABSTRACT FROM AUTHOR]

Abstract Background Almost 20% of neonates experience pain during delivery or the period following birth. Aim To describe the practices of pain assessment in the maternity wards in the greater Paris area, France. Methods An e-mail questionnaire was sent to each practitioner in the 96 maternity units in Île de France between December 2013 and February 2014. Results In all, 63 (65%) questionnaires were completed. Pain was assessed in 43 (68%) maternity units, mostly using the French scale "échelle de douleur et d'inconfort du nouveau-né" (EDIN). In total, 20 maternity units (32%) reported no pain assessment, mainly because they considered it to be too time-consuming, or because they argued that no pain scale was adequate; they relied on clinical signs or on the obstetric history for assessing and treating pain. About 40% of the maternity units using the EDIN scale judged it unsuitable for evaluating pain in term neonates in maternity units. Conclusion This first regional study on pain assessment in the maternity ward showed that nearly two thirds of centers assessed pain. This rate may be overestimated because of the reporting method used. The EDIN scale is the most widely used tool but seems unsuitable especially for the delivery room setting. Studies should be conducted to test other tools for assessing neonatal pain in the delivery room. [ABSTRACT FROM AUTHOR]

Abstract: Early life trauma has been linked to increased risks for anxiety, depression, and chronic pain. We used rodent models of acute and inflammatory neonatal pain to explore effects on fear conditioning and somatosensory function. Hindpaw needle pricks or handling on postnatal days (PNDs) 1–7 caused lasting impacts on affective and somatosensory function when assessed at later ages, PNDs 24 (postweaning), 45 (adolescence), or 66 (adulthood). First, auditory, but not contextual, freezing was mildly disrupted regardless of age. Second, a profound postfear conditioning tactile hypersensitivity was observed in neonatally stressed, postweaning rats. In the absence of fear conditioning, the mechanical hypersensitivity was not observed, consistent with a two‐hit model of psychopathology. Injections of 2% α‐carrageenan did not have the same lasting impact but was slightly protective against observed effects of neonatal vehicle injections. Basal and elicited corticosterone levels postweaning were not altered by neonatal pain or handling. These data demonstrate that neonatal adversity can have lasting impacts on affective and somatosensory function that differs regardless of age. [ABSTRACT FROM AUTHOR]

Objectives: To compare individual efficacy and additive effects of pain control interventions in preterm neonates.Design: Randomized controlled trialSetting: Level-3 University affiliated neonatal intensive care unit.Participants: 200 neonates (26-36 wk gestational age) requiring heel-prick for bedside glucose assessment. Exclusion criteria were neurologic impairment and critical illness precluding study interventions.Intervention: Neonates were randomly assigned to Kangaroo mother care with Music therapy, Music therapy, Kangaroo Mother care or Control (no additional intervention) groups. All groups received expressed breast milk with cup and spoon as a baseline pain control intervention.Main outcome measure: Assessment of pain using Premature Infant Pain Profile (PIPP) score on recorded videos.Results: The mean (SD) birth weight and gestational age of the neonates was 1.9 (0.3) kg and 34 (2.3) wk, respectively. Analysis of variance showed significant difference in total PIPP score across groups (P<0.001). Post-hoc comparisons using Sheffe’s test revealed that the mean (SD) total PIPP score was significantly lower in Kangaroo mother care group [7.7 (3.9) vs. 11.5 (3.4), 95% CI(-5.9, -1.7), P<0.001] as well as Kangaroo mother care with Music therapy group [8.5 (3.2) vs. 11.5 (3.4), 95%CI (-5.1, -0.9), P=0.001] as compared to Control group. PIPP score was not significantly different between Control group and Music therapy group.Conclusions: Kangaroo mother care with and without Music therapy (with expressed breast milk) significantly reduces pain on heel-prick as compared to expressed breast milk alone. Kangaroo mother care with expressed breast milk should be the first choice as a method for pain control in preterm neonates. [ABSTRACT FROM AUTHOR]