脑岛、杏仁核是疼痛恐惧形成的重要神经网络中心。疼痛恐惧增强了慢性疼痛患者的疼痛知觉体验, 进而加剧抑郁、焦虑情绪和功能损伤程度。脑岛、杏仁核、前额皮层和前扣带回是疼痛恐惧影响疼痛知觉的重要神经基础。通过认知方法干预疼痛恐惧可以改善患者的抑郁、焦虑情绪, 减少功能损伤。未来研究应拓展疼痛恐惧的测量工具, 采用功能磁共振成像技术进一步揭示疼痛恐惧影响慢性疼痛患者疼痛知觉的神经机制。

OBJECTIVE: To determine whether caregivers with more extreme emotional availability scores enact different levels of soothing behaviors and whether infants of these caregivers differ in their pain scores across the first year of life. METHODS: Cross-sectional analyses (analyses of variance and multivariate analyses of variance) were conducted with parent-infant dyads at 2, 4, 6, and 12 months of age who had extreme caregiver emotional availability scores. Pain scores were examined using a minimum clinically significant difference. RESULTS: Infants with lower pain scores had caregivers who were in the high emotional availability group. This effect was most pronounced during the regulatory period at 2 months, and clinically significant differences in pain scores were found during the regulatory period at 12 months. Physical comforting and/or rocking were characteristic of caregivers with high emotional availability. CONCLUSION: This study suggests that caregiver emotional availability, in the extremes, do have clinically meaningful relationships with infant pain regulation.

0.1). Pain-related [HbO2] increases were more pronounced in male neonates (p

A systematic scoping search to describe the neurophysiological methods used in infant acute pain assessment research was conducted. Of the 2411 abstracts screened, 19 articles were retained. Nine studies utilised near-infrared spectroscopy (NIRS), two utilised functional magnetic resonance imaging (fMRI), and eight utilised electroencephalography (EEG). There was methodological variability in studies utilising NIRS, whereas EEG and fMRI studies reported consistent methods. Of the eight EEG studies, six identified a nociceptive-specific event-related potential. CONCLUSION: While more methodologically rigorous studies are needed, ERPs appear to hold some promise as indicators of infant nociception during clinical procedures to supplement existing measures.

2.5 kg on sedative or analgesic medications appeared to have procedure-related accentuation and sustained elevation in scale scores, whereas swaddling seemed to provide little added benefit. CONCLUSIONS: The pain scale scores identify changes in an infant's behavior/physiologic state. It is unclear whether these changes are totally]]>

Methods: Infants born very preterm (N = 86; 24-32 weeks gestational age) were followed prospectively from birth, and studied with magnetic resonance imaging, 3-dimensional magnetic resonance spectroscopic imaging, and diffusion tensor imaging: scan 1 early in life (median, 32.1 weeks) and scan 2 at term-equivalent age (median, 40 weeks). We calculated N-acetylaspartate to choline ratios (NAA/choline), lactate to choline ratios, average diffusivity, and white matter fractional anisotropy (FA) from up to 7 white and 4 subcortical gray matter regions of interest. Procedural pain was quantified as the number of skin-breaking events from birth to term or scan 2. Data were analyzed using generalized estimating equation modeling adjusting for clinical confounders such as illness severity, morphine exposure, brain injury, and surgery.Results: After comprehensively adjusting for multiple clinical factors, greater neonatal procedural pain was associated with reduced white matter FA (beta = -0.0002, p = 0.028) and reduced subcortical gray matter NAA/choline (beta = -0.0006, p = 0.004). Reduced FA was predicted by early pain (before scan 1), whereas lower NAA/choline was predicted by pain exposure throughout the neonatal course, suggesting a primary and early effect on subcortical structures with secondary white matter changes.Interpretation: Early procedural pain in very preterm infants may contribute to impaired brain development. ANN NEUROL 2012;71:385-396]]>

Recent research has demonstrated that parental behaviors have an important impact upon child and adolescent pain outcomes. At present, however, we do not know which parents engage in particular behaviors and why. In 2 studies, the impact of parental catastrophizing about their child's pain upon parental tendency to stop their child's pain-inducing activity was investigated. Further, the mediating role of parental distress was explored. In study 1, a sample of schoolchildren (n = 62; M = 12.48 years; SD = 1.72) took part in a cold-pressor task. In study 2, a clinical sample of adolescents with chronic pain (n = 36; M = 15.68 years; SD = 1.85) performed a 2-min walking task designed as a pain-inducing activity. In both studies, the accompanying parent was asked to watch their child performing the pain task. Findings revealed, for both studies, that parents with a high level of catastrophic thinking about their child's pain experienced more distress and a greater behavioral tendency of wanting to stop their child's pain-inducing activity. Further, parental feelings of distress mediated the relationship between parental catastrophic thinking and parents' tendency to restrict their child's activity. The findings are discussed in light of an affective-motivational conceptualization of pain and pain behavior. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V.

Emotion regulation and quality of attachment are closely linked. It has been proposed here that one influence on individual differences in emotion regulation may be a child's attachment history. Individuals characterized by the flexible ability to accept and integrate both positive and negative emotions are generally securely attached; on the other hand, individuals characterized by either limited or heightened negative affect are more likely to be insecurely attached. While acknowledging the role of infant temperament, I have focused on the role of social factors in examining the link between emotion regulation and attachment. The approach to emotion regulation taken here--that emotion regulation is adaptive in helping a child attain her goals--is esentially a functionalist approach (Bretherton et al., 1986; Campos et al., 1983), consistent with earlier views of emotions as important regulators of interpersonal relationships (Charlesworth, 1982; Izard, 1977). It has been proposed that patterns of emotion regulation serve an important function for the infant: the function of maintaining the relationship with the attachment figure. Emotion regulation has been described as serving this function in two ways. First, the function of maintaining the relationship is thought to be served when infant emotion regulation contributes to the infant's more generalized regulation of the attachment system in response to experiences with the caregiver. Infants who have experienced rejection (insecure/avoidant infants) are thought to minimize negative affect in order to avoid the risk of further rejection. Infants whose mothers have been relatively unavailable or inconsistently available (insecure/ambivalent infants) are thought to maximize negative affect in order to increase the likelihood of gaining the attention of a frequently unavailable caregiver. Both these patterns of emotion regulation help ensure that the child will remain close to the parent and thereby be protected. Second, the function of maintaining the attachment relationship is thought to be served when the infant signals to the parent that she will cooperate in helping maintain the parent's own state of mind in relation to attachment. The minimizing of negative affect of the avoidant infant signals that the infant will not seek caregiving that would interfere with the parent's dismissal of attachment. The heightened negative emotionality of the ambivalent infant signals to the parent that the infant needs her and thus helps maintain a state of mind in which attachment is emphasized. The approach to emotion regulation presented here is congruent with much work examining the socialization of emotions (Lewis & Saarni, 1985; Thompson, 1990).

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments. In humans, however, undesirable, excessive or chronic pain is a common and major societal burden for which available medical treatments are currently suboptimal. New therapeutic options have recently been derived from studies of individuals with congenital insensitivity to pain (CIP). Here we identified 10 different homozygous mutations in PRDM12 (encoding PRDI-BF1 and RIZ homology domain-containing protein 12) in subjects with CIP from 11 families. Prdm proteins are a family of epigenetic regulators that control neural specification and neurogenesis. We determined that Prdm12 is expressed in nociceptors and their progenitors and participates in the development of sensory neurons in Xenopus embryos. Moreover, CIP-associated mutants abrogate the histone-modifying potential associated with wild-type Prdm12. Prdm12 emerges as a key factor in the orchestration of sensory neurogenesis and may hold promise as a target for new pain therapeutics.

Ipsi- and contralateral patterns of lower limb nociceptive reflex responses were studied in 6 normal subjects in free standing position. Once the position was stabilized, only ankle extensor muscles showed consistent tonic activity while ankle flexors and knee extensors and flexors were virtually silent. Reflex responses, elicited by painful electrical stimuli to the skin of the plantar and dorsal aspect of the foot, were recorded from ipsi- and contralateral quadriceps (Q), biceps femoris (Bic), tibialis anterior (TA) and soleus (Sol) muscles. Plantar foot stimulation evoked a large excitatory response in the ipsilateral TA at about 80 ms and a smaller responses in Bic and Q at 70 ms and 110 ms, respectively. Ipsilateral excitatory effects after dorsal foot stimulation consisted of a Bic response at about 75 ms. In addition to excitatory effects, both plantar and dorsal foot stimulation evoked long-lasting suppression of ipsilateral Sol background activity starting at about 60 ms. Contralaterally, the only nociceptive effects after plantar or dorsal foot stimulation were a small excitatory response of Sol at about 85 ms. Evidence is provided that only excitatory responses were contingent upon nociceptive volley. The main mechanical effects seen after plantar stimulation were dorsiflexion of the foot without loss of heel contact with the floor; no withdrawal response of the foot followed nociceptive dorsal stimulation. Our main conclusion is that only reflex nociceptive responses serving to avoid the stimulus without conflicting with limb support function are expressed. The mechanisms reconciling nociceptive action and postural function of the lower limbs are discussed.

When and how infants begin to discriminate noxious from innocuous stimuli is a fundamental question in neuroscience [1]. However, little is known about the development of the necessary cortical somatosensory functional prerequisites in the intact human brain. Recent studies of developing brain networks have emphasized the importance of transient spontaneous and evoked neuronal bursting activity in the formation of functional circuits [2, 3]. These neuronal bursts are present during development and precede the onset of sensory functions [4, 5]. Their disappearance and the emergence of more adult-like activity are therefore thought to signal the maturation of functional brain circuitry [2, 4]. Here we show the changing patterns of neuronal activity that underlie the onset of nociception and touch discrimination in the preterm infant. We have conducted noninvasive electroencephalogram (EEG) recording of the brain neuronal activity in response to time-locked touches and clinically essential noxious lances of the heel in infants aged 28-45 weeks gestation. We show a transition in brain response following tactile and noxious stimulation from nonspecific, evenly dispersed neuronal bursts to modality-specific, localized, evoked potentials. The results suggest that specific neural circuits necessary for discrimination between touch and nociception emerge from 35-37 weeks gestation in the human brain.

The descending pain modulatory system (DPMS) constitutes a network of widely distributed brain regions whose integrated function is essential for effective modulation of sensory input to the central nervous system and behavioural responses to pain. Animal studies demonstrate that young rodents have an immature DPMS, but comparable studies have not been conducted in human infants. In Goksan et al. (2015) we used functional MRI (fMRI) to show that pain-related brain activity in newborn infants is similar to that observed in adults. Here, we investigated whether the functional network connectivity strength across the infant DPMS influences the magnitude of this brain activity. FMRI scans were collected while mild mechanical noxious stimulation was applied to the infant's foot. Greater pre-stimulus functional network connectivity across the DPMS was significantly associated with lower noxious-evoked brain activity (p = 0.0004, r = -0.86, n = 13), suggesting that in newborn infants the DPMS may regulate the magnitude of noxious-evoked brain activity.

This paper describes the development and evaluation of the Pain Assessment Tool (PAT), a scoring system that was developed by a group of neonatal nurses to assess neonates' pain. To test the practical application of the tool and to compare the scoring system with nurses' subjective pain assessments, a pilot study was conducted with a sample of 20 neonates during the 24 hours following their surgery. The study found that PAT effectively quantified neonates' pain and that PAT scores reflected nurses' perceptions of the pain experienced by neonates. Based on the PAT scores, 15 babies experienced discomfort that required nursing comfort measures and eight babies needed both comfort measures and analgesia to relieve pain. Recommendations for future use of the Pain Assessment Tool are discussed.

OBJECTIVE: The relationship between attachment, temperamental fear, and pain-related distress was examined in a sample of 130 caregiver-infant dyads to explore the differential susceptibility hypothesis. METHOD: Infant distress was measured during routine immunization at 12 months, and attachment and temperamental fear were measured at 12 to 18 months (meanage = 13.74, SD = 1.35) using the Strange Situation Procedure and parent-rated Infant Behavior Questionnaire-Revised, respectively. RESULTS: Immediately before immunization, avoidant infants exhibited significantly less distress than secure infants. Temperamental fear moderated the relationship between attachment and regulation; under conditions of high temperamental fear, avoidant infants regulated distress more slowly than secure infants, whereas under conditions of low temperamental fear, secure infants regulated distress more slowly than avoidant and disorganized infants. CONCLUSION: The findings suggest that attachment interacts with extremes in temperamental fear to produce differences in the regulation of distress. The results partially support the differential susceptibility hypothesis.

We have developed a neonatal pain assessment tool CRIES. The tool is a ten point scale similar to the APGAR score (Apgar 1953). It is an acronym of five physiological and behavioural variables previously shown to be associated with neonatal pain. C--Crying; R--Requires increased oxygen administration; I--Increased vital signs; E--Expression; S--Sleeplessness. We have tested CRIES for validity and reliability. This report is the result of that testing. We have found CRIES to be valid, reliable and well accepted by neonatal nurses.

Infants, including newborn babies, experience pain similarly and probably more intensely than older children and adults. They are also at risk of adverse long term effects on behaviour and development, through inadequate attention towards pain relief in early life. However, the issue of analgesia in young babies has been largely neglected in most clinical settings, despite subjecting them to painful diagnostic and therapeutic procedures. Several therapeutic and preventive strategies, including systemic and local pharmacological and non-pharmacological interventions, are reported to be effective in relieving pain in infants. A judicious application of these interventions, backed by awareness and sensitivity to pain perception, on the part of the caregivers is likely to yield the best results. This article is a review of the mechanisms of pain perception, objective assessment, and management strategies of pain in infants.

UNLABELLED: Skepticism toward infant pain characterized much of 20th century research and clinical practice, with infant surgery routinely conducted with minimal or no anesthesia into the 1980s. This paper offers a historical exploration of how this view became common by reviewing and analyzing the experimental infant pain research of the 19th and early 20th centuries that contributed to the development of infant pain denial. These experiments used pinprick and electric shock, and the results were generally interpreted as evidence of infants' underdeveloped pain perception, attributed to their lack of brain maturation. Even clear responses to noxious stimuli were often dismissed as reflex responding. Later these experimental findings were used by anesthesiologists to support the lessened use of anesthesia for infants. Based on the reviewed literature, this paper suggests that 4 interrelated causes contributed to the denial of infant pain: the Darwinian view of the child as a lower being, extreme experimental caution, the mechanistic behaviorist perspective, and an increasing emphasis on brain and nervous system development. Ultimately this history can be read as a caution to modern researchers to be aware of their own biases, the risks of null hypothesis testing, and a purely mechanistic view of infants. PERSPECTIVE: This article reviews the history of 19th and early 20th century infant pain research, tracing how the widely accepted belief that infants could not feel pain developed in the period prior to the growing acceptance of infant pain. Four interrelated causes are posited to help explain the tolerance of infant pain denial until recent times.

A chart review was conducted of the records of 90 children and 90 adults, randomly selected and matched for sex and diagnosis, to investigate analgesic usage. Four diagnostic categories (hernias, appendectomies, burns, and fractured femurs) at two hospitals were examined. Results revealed that adults received an average of 2.2 doses of narcotics per day, whereas children received 1.1 (P = .0001). Significant differences in dosing were noted between the diagnostic categories. Diagnoses associated with a longer hospital stay showed a greater discrepancy between narcotic usage in children and adults. Hospital differences were also significant (P = .004) with more doses per day administered at the urban hospital than the rural one. Infants and young children were less likely than older children to have narcotics ordered for them, but, if ordered, frequency of administration was similar for all children. Our study demonstrates that children and adults with the same diagnoses are treated differently as regards narcotic administration. Further research is necessary to determine whether these results represent a difference in pain tolerance in children or a lack of recognition of their discomfort.

Methods:;The PIPP was revised to enhance validity and feasibility. To validate the PIPP-R, data from 2 randomized cross-over studies were utilized to: (1) calculate and compare PIPP and PIPP-R scores in extremely low gestational age infants undergoing a painful and nonpainful event (N=52; dataset #1) and (2) calculate and compare PIPP and PIPP-R scores in assessing the effectiveness of (a) sucrose, (b) non-nutritive sucking (NNS)+sucrose, and (c) facilitated tucking+NNS+sucrose during heel lance (N=85; dataset #2). Pearson correlations between PIPP and PIPP-R scores were calculated, and Student t tests and 1-way analysis of variance were used to determine construct validity during painful and nonpainful events. To establish feasibility, a survey of 31 Neonatal Intensive Care Unit nurses was conducted.Results:;PIPP-R scores were significantly lower during nonpainful (mean, 8.3; SD=2.9) compared with painful (mean, 9.9; SD=3.1; t(95)=4.51, P=0.036) events in extremely low gestational age infants in dataset #1. In dataset #2, PIPP-R scores were significantly lower in infants 25 to 41 weeks gestation in the group receiving NNS+sucrose compared with the other 2 groups (F-2,F-79=2.9, P Discussion:;Initial construct validation and feasibility of the PIPP-R was demonstrated. Further testing with infants of varying gestational ages, diagnoses, and pain conditions is required; as is exploration of PIPP-R in relation to other types of physiological and cognitive responses.]]>

Neuron that address our understanding of the pain process and possible solutions to the problem from both cellular- and systems-level viewpoints.Our understanding of the neural correlates of pain perception in humans has increased significantly since the advent of neuroimaging. Relating neural activity changes to the varied pain experiences has led to an increased awareness of how factors (e.g., cognition, emotion, context, injury) can separately influence pain perception. Tying this body of knowledge in humans to work in animal models of pain provides an opportunity to determine common features that reliably contribute to pain perception and its modulation. One key system that underpins the ability to change pain intensity is the brainstem's descending modulatory network with its pro- and antinociceptive components. We discuss not only the latest data describing the cerebral signature of pain and its modulation in humans, but also suggest that the brainstem plays a pivotal role in gating the degree of nociceptive transmission so that the resultant pain experienced is appropriate for the particular situation of the individual.]]>

BACKGROUND: Neonates cared for in neonatal intensive care units are exposed to many painful and stressful procedures that, cumulatively, could impact later neurodevelopmental outcomes. However, a systematic analysis of these effects is yet to be reported. OBJECTIVES: The aim of this research was to review empirical studies examining the association between early neonatal pain experiences of preterm infants and the subsequent developmental outcomes of these children across different ages. METHODS: The literature search was performed using the PubMed, PsycINFO, Lilacs, and SciELO databases and included the following key words:

The majority of infants born very preterm (24-32 wk gestational age) now survive; however, long-term neurodevelopmental and behavioral problems remain a concern. As part of their neonatal care, very preterm infants undergo repeated painful procedures during a period of rapid brain development and programming of stress systems. Infants born this early have the nociceptive circuitry required to perceive pain, however, their sensory systems are functionally immature. An imbalance of excitatory vs. inhibitory processes leads to increased nociceptive signaling in the central nervous system. Specific cell populations in the central nervous system of preterm neonates are particularly vulnerable to excitoxicity, oxidative stress, and inflammation. Neonatal rat models have demonstrated that persistent or repeated pain increases apoptosis of neurons, and neonatal pain and stress lead to anxiety-like behaviors during adulthood. In humans, greater exposure to neonatal pain-related stress has been associated with altered brain microstructure and stress hormone levels, as well as with poorer cognitive, motor, and behavioral neurodevelopment in infants and children born very preterm. Therefore, it is important that pain-related stress in preterm neonates is accurately identified, appropriately managed, and that pain management strategies are evaluated for protective or adverse effects in the long term.

OBJECTIVES: Capacities for self-regulation that influence infant adaptation to noxious stimulation require investigation of changes in behavior over time. Prenatal exposure to maternal depression and anxiety (MDA) has been linked to altered infant pain reactivity; however, findings are inconclusive about MDA dynamic impacts on recovery. This study quantified the temporal profile of behavioral response and recovery to routine heel lance (HL) of infants with and without prenatal-MDA exposure. Aims were to examine whether MDA were associated with alterations in time-based measures of infant behavior and sequential patterning in pain expression. MATERIALS AND METHODS: Videotaped facial, body, and cry behaviors of 21 full-term newborns were coded second-by-second for the duration of HL (baseline, HL, Post-HL) using validated behavioral coding systems. Mean heart rate and proportion of time infants spent exhibiting behavioral measures were compared between infant groups and over subphases of HL. Simple regressions, latency, and Yule-Q measures of effect size examined which behaviors were predicted by prenatal-MDA and magnitude of sequential association between first and subsequent behavior. RESULTS: During HL, all infants reacted immediately and substantially on heart rate, facial, body, and cry measures. Facial reactivity was followed within 2 seconds by body and cry behavior. There were no group differences in magnitude of initial behavioral reactions, but during Post-HL, MDA-exposed infants spent more time crying in a weak/exhausted manner and displayed strained and erratic limb movement and immobility. CONCLUSIONS: Temporal measures can further help in understanding of infant complex behavioral responses to pain. Delayed recovery in MDA-exposed infants suggested diminished capacities for self-regulation of noxious distress.