Manon Ranger

Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm

Background Altered brain development is evident in children born very preterm (24–32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age. Methods 42 right-handed children born very preterm (24–32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. Results After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes. Conclusions In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.

Early repetitive pain in preterm infants in relation to the developing brain

Infants born preterm (<37 weeks of gestation) are particularly vulnerable to procedural stress and pain exposure during neonatal intensive care, at a time of rapid and complex brain development. Concerns regarding effects of neonatal pain on brain development have long been expressed. However, empirical evidence of adverse associations is relatively recent. Thus, many questions remain to be answered. This review discusses the short- and long-term effects of pain-related stress and associated treatments on brain maturation and neurodevelopmental outcomes in children born preterm. The current state of the evidence is presented and future research directions are proposed.

Internalizing behaviours in school‐age children born very preterm are predicted by neonatal pain and morphine exposure

Greater neonatal pain is associated with higher internalizing behaviours in very preterm infants at 18 months corrected age, but it is unknown whether this relationship persists to school age. Moreover, it is unclear whether morphine ameliorates or exacerbates the potential influence of neonatal pain/stress on internalizing behaviours. We examined whether neonatal pain‐related stress is associated with internalizing behaviours at age 7 years in children born very preterm, and whether morphine affects this relationship.

Neonatal Pain and Infection Relate to Smaller Cerebellum in Very Preterm Children at School Age

OBJECTIVE To examine whether specific neonatal factors differentially influence cerebellar subregional volumes and to investigate relationships between subregional volumes and outcomes in very preterm children at 7 years of age. STUDY DESIGN Fifty-six children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-dimensional T(1)-weighted neuroimaging at median age 7.6 years. Children with severe brain injury were excluded. Cerebellar subregions were automatically segmented using the multiple automatically generated templates algorithm. The relation between cerebellum subregional volumes (adjusted for total brain volume and sex) and neonatal clinical factors were examined using constrained principal component analysis. Cognitive and visual-motor integration functions in relation to cerebellar volumes were also investigated. RESULTS Higher neonatal procedural pain and infection, as well as other clinical factors, were differentially associated with reduced cerebellar volumes in specific subregions. After adjusting for clinical risk factors, neonatal procedural pain was distinctively associated with smaller volumes bilaterally in the posterior VIIIA and VIIIB lobules. Specific smaller cerebellar subregional volumes were related to poorer cognition and motor/visual integration. CONCLUSIONS In very preterm children, exposure to painful procedures, as well as additional neonatal risk factors such as infection, were associated with reduced cerebellar volumes in specific subregions and poorer outcomes at school age.

Neonatal pain and COMT Val158Met genotype in relation to serotonin transporter (SLC6A4) promoter methylation in very preterm children at school age

Children born very preterm are exposed to repeated neonatal procedures that induce pain and stress during hospitalization in the neonatal intensive care unit (NICU). The COMT Val158Met genotype is involved with pain sensitivity, and early life stress is implicated in altered expression of methylation of the serotonin transporter. We examined: (1) whether methylation of the serotonin transporter gene (SLC6A4) promoter differs between very preterm children and full-term controls at school age, (2) relationships with child behavior problems, and (3) whether the extent of neonatal pain exposure interacts with the COMT Val158Met genotype to predict SLC6A4 methylation at 7 years in the very preterm children. We examined the associations between the COMT genotypes, neonatal pain exposure (adjusted for neonatal clinical confounders), SLC6A4 methylation and behavior problems. Very preterm children had significantly higher methylation at 7/10 CpG sites in the SLC6A4 promoter compared to full-term controls at 7 years. Neonatal pain (adjusted for clinical confounders) was significantly associated with total child behavior problems on the Child Behavior Checklist (CBCL) questionnaire (adjusted for concurrent stressors and 5HTTLPR genotype) (p = 0.035). CBCL Total Problems was significantly associated with greater SLC6A4 methylation in very preterm children (p = 0.01). Neonatal pain (adjusted for clinical confounders) and COMT Met/Met genotype were associated with SLC6A4 promoter methylation in very preterm children at 7 years (p = 0.001). These findings provide evidence that both genetic predisposition and early environment need to be considered in understanding susceptibility for developing behavioral problems in this vulnerable population.

A multidimensional approach to pain assessment in critically ill infants during a painful procedure.

Objectives:Inferring the pain level of a critically ill infant is complex. The ability to accurately extract the appropriate pain cues from observations is often jeopardized when heavy sedation and muscular blocking agents are administered. Near-infrared spectroscopy is a noninvasive method that may provide the bridge between behavioral observational indicators and cortical pain processing. We aimed to describe regional cerebral and systemic hemodynamic changes, as well as behavioral reactions in critically ill infants with congenital heart defects during chest-drain removal after cardiac surgery. Methods:Our sample included 20 critically ill infants with congenital heart defects, less than 12 months of age, admitted to the cardiac intensive care unit after surgery. Results:Cerebral deoxygenated hemoglobin concentrations significantly differed across the epochs (ie, baseline, tactile stimulus, noxious stimulus) (P=0.01). Physiological systemic responses and Face Leg Activity Cry Consolability (FLACC) pain scores differed significantly across the events (P<0.01). The 3 outcome measures were not found to be associated with each other. Mean FLACC pain scores during the painful procedure was 7/10 despite administration of morphine. Midazolam administration accounted for 36% of the variance in pain scores. Discussion:We demonstrated with a multidimensional pain assessment approach that significant cerebral, physiological, and behavioral activity was present in response to a noxious procedure in critically ill infants despite the administration of analgesic treatment. Considering that the sedating agent significantly dampened pain behaviors, assessment of cerebral hemodynamic in the context of pain seems to be an important addition.

Temperament and pain response: a review of the literature.

Pain is a subjective and uniquely lived experience. Because reactions to pain vary so widely from one person to another, and better pain management remains a major issue in our attempt to resolve pain and suffering of varying populations, we need to generate interventions that better target interindividual variations. One research avenue could be the study of each persons own biologic and psychologic makeup. Within this path, individual temperament is a rich and fascinating terrain to consider. The purpose of the present article is to describe the relationship between individual temperament and pain response (and pain perception) by searching the literature. Nursing implications regarding this theme are then discussed.

Toward a new approach for the detection of pain in adult patients undergoing cardiac surgery: Near-infrared spectroscopy—A pilot study

OBJECTIVE This pilot study examined the discriminant validity and criterion validity of regional cerebral oxygenation measurement (rSO₂), using the near-infrared spectroscopy (NIRS) technique (INVOS-4100 system, Somanetics, Troy, MI) for measuring pain during nociceptive procedures in adults undergoing cardiac surgery. METHODS A repeated-measures, within-subjects design was used, and 40 adult patients participated. Data collection was completed during 2 test periods: (1) while patients were awake, before the induction of anesthesia (first test period); and (2) after the induction of anesthesia, while patients remained under the effects of anesthesia (second test period). Each test period included a baseline, a tactile stimulus (skin disinfection), nociceptive stimuli (e.g., intravenous and arterial line insertions, sternal bone incision and thorax opening), and a postprocedure evaluation. RESULTS Increased rSO₂ values (P < .001) were acquired during nociceptive procedures in both test periods. No significant associations were evident between rSO₂, pain behaviors, and the patients self-report of pain intensity, but this may be attributable to a low range of variability. CONCLUSIONS Although further research is needed in critically ill adult patients undergoing more painful procedures, the NIRS may become a promising technique for assessing pain.

Neonatal Invasive Procedures Predict Pain Intensity at School Age in Children Born Very Preterm

Introduction:Children born very preterm display altered pain thresholds. Little is known about the neonatal clinical and psychosocial factors associated with their later pain perception. Objective:We aimed to examine whether the number of neonatal invasive procedures, adjusted for other clinical and psychosocial factors, was associated with self-ratings of pain during a blood collection procedure at school age in children born very preterm. Materials and Methods:56 children born very preterm (24 to 32 weeks gestational age), followed longitudinally from birth, and free of major neurodevelopmental impairments underwent a blood collection by venipuncture at age 7.5 years. The children’s pain was self-reported using the Coloured Analog Scale and the Facial Affective Scale. Parents completed the Child Behavior Checklist and the State-Trait Anxiety Inventory. Pain exposure (the number of invasive procedures) and clinical factors from birth to term-equivalent age were obtained prospectively. Multiple linear regression was used to predict children’s pain self-ratings from neonatal pain exposure after adjusting for neonatal clinical and concurrent psychosocial factors. Results:A greater number of neonatal invasive procedures and higher parent trait-anxiety were associated with higher pain intensity ratings during venipuncture at age 7.5 years. Fewer surgeries and lower concurrent child externalizing behaviors were associated with a higher pain intensity. Conclusions:In very preterm children, exposure to neonatal pain was related to altered pain self-ratings at school age, independent of other neonatal factors. Neonatal surgeries and concurrent psychosocial factors were also associated with pain ratings.

Innovating in pain assessment of the critically ill: exploring cerebral near-infrared spectroscopy as a bedside approach.

Nurses play a crucial role in the evaluation and treatment of pain in the critically ill patient. This responsibility is all the more critical with this particular population because many may not be able to self-report their pain level and the typical behavioral signs of pain may be subtle or absent. According to recent recommendations, vital signs should not be used as primary indicators of pain but rather considered as a cue to begin further assessment. Other than vital signs, human brain reactivity to pain has been extensively studied with the use mainly of magnetic resonance imaging and positron-emission tomography. However, the use of these sophisticated methods may be unrealistic in the critically ill. Of interest to assessing these patients in a clinical setting is the noninvasive measurement of regional cerebral tissue oxygenation with the near-infrared spectroscopy (NIRS) technique. There are indications that NIRS is capable of detecting the cerebral hemodynamic changes associated with sensory stimuli, including pain. The objective of this review paper is to provide nurses with a better understanding of NIRS technology, including a review of the literature on functional studies that have used NIRS in critically ill populations, and how it could be used in both research and practice. Current NIRS techniques have well recognized limitations which must be considered carefully during the measurement and interpretation of signals. Thus, its clinical use is yet to be fully established. Nonetheless, cerebral NIRS technique as an approach to assess brain activity in response to pain should not be abandoned.