Do school-aged children with burn injuries during infancy show stress-induced activation of pain inhibitory mechanisms?

There is evidence in humans and animals that neonatal and early infant pain and stress may sensitize excitatory pain pathways. Possibly such experiences may result in long-term diminished activation of phasic endogenous pain inhibitory mechanisms. We studied stress-induced activation of endogenous pain inhibitory mechanisms in school-aged children (10-16 years) who had suffered moderate (N= =12) or severe (N=10) burn injuries in infancy (6-24 months of age) and 20 controls. Before and after the stress phase, pain threshold and pain tolerance (heat, pressure, ischemic pain) were assessed. Stress was successfully induced in all children as reflected by increases in heart rate, blood pressure and perceived stress. In the controls, there was evidence for stress-induced hypoalgesia as reflected by significant increases in heat pain threshold, heat pain tolerance and pressure pain tolerance. Pressure pain thresholds were not significantly altered. A similar pattern was observed in the moderately burned children. By contrast, children with severe burn injuries failed to show significant stress-related changes in heat and pressure pain sensitivity. In all groups, ischemic pain sensitivity was elevated post stress. The children reported being more distressed by the perceived loss of strength than by pain and had difficulties differentiating between the two. It is possible that ischemic pain may be less suitable for measuring pain sensitivity in children. The present study provides first evidence that pain and stress exposure due to severe burns in infancy may be associated with an attenuated stress-induced activation of phasic endogenous pain inhibitory mechanisms later in childhood and adolescence.

Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study.

Due to maturation-related plasticity of the developing nociceptive system, neonatal nociceptive input, as induced by medical procedures in the neonatal intensive care unit (NICU), may cause long-term alterations in pain processing. Using functional magnetic resonance imaging, this study investigated the cerebral pain response in school-aged children and adolescents (11-16 yr) with experience in a NICU after preterm (or=37 weeks gestational age, N=9) as compared to fullterm control children without early hospitalization (N=9). NICU children had been recruited retrospectively among former patients of the Children's University Hospital Mannheim. All children had participated in our previous studies [46,49] entailing psychophysical measurements. In response to tonic (30s) heat stimuli of individually adjusted moderate pain intensity, which were of comparable temperature across groups, the preterm but not the fullterm NICU children exhibited significant activations in a number of brain regions (thalamus, anterior cingulate cortex, cerebellum, basal ganglia, and periaquaeductal gray) that were not significantly activated in controls. The preterms showed significantly higher activations than controls in primary somatosensory cortex, anterior cingulate cortex, and insula. This exaggerated brain response was pain-specific and was not observed during non-painful warmth stimulation. Preterms' continuous pain ratings revealed a tendency for increased sensitization within and a lack of habituation across trials. In highly vulnerable children such as preterms, neonatal nociceptive input may, aside from other neurodevelopmental consequences, persistently increase the gain within pain pathways.

Do burn injuries during infancy affect pain and sensory sensitivity in later childhood?

Studies in animals and humans suggest that neonatal and early infant pain or stress experiences can induce long-term alterations in somatosensory and pain processing. We studied pain and sensory sensitivity in school-aged children (9-16 years) who had suffered moderate (N=24) or severe (N=24) burn injuries in infancy (6-24 months of age) and 24 controls. Quantitative sensory testing entailing detection and pain thresholds for thermal and mechanical stimuli and perceptual sensitization to tonic heat and repetitive mechanical stimuli was performed. Two testing sites (thenar, trigeminal region), both not affected by the burn injury, were used to determine whether there are global changes in pain sensitivity. The result pattern suggests a differential impact of burn severity. Compared to controls, moderately burned children showed significantly higher mechanical detection thresholds (thenar) and significantly lower mechanical pain thresholds and significantly greater perceptual sensitization to repetitive mechanical stimuli (both testing sites). No significant alterations were observed for thermal stimuli. In contrast, severely burned children showed, compared to controls, primarily alterations in thermal pain sensitivity (elevated pain thresholds at both testing sites, significantly greater perceptual sensitization at the thenar). In these children, mechanical pain sensitivity and detection thresholds were not consistently altered. This differential pattern of altered sensory and pain sensitivity may reflect differences in experienced stress, pain and analgesic treatment between moderately and severely burned children. Most importantly, our findings suggest that early traumatic and painful injuries, such as burns, can induce global, long-term alterations in sensory and pain processing.

Responses to pain in school-aged children with experience in a neonatal intensive care unit: cognitive aspects and maternal influences.

Previously, it was shown that school-aged (9-14 yr) preterm and fullterm children with neonatal pain exposure exhibit elevated heat pain thresholds and heightened perceptual sensitization to tonic painful heat when tested under standard conditions [Hermann C, Hohmeister J, Demirakca S, Zohsel K, Flor H. Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain 2006;125:278-85]. Here, changes in the psychosocial context of pain responses in these children, who had been hospitalized >or=7 days after birth including >or=3 days of treatment in a neonatal intensive care unit (NICU), are reported. Nineteen preterm (or=37 weeks gestational age) with NICU experience, recruited retrospectively and selected based on strict exclusion criteria, and 20 fullterm control children participated. Preterm NICU children endorsed more pain catastrophizing as compared to controls. Mothers of preterm children, who had been more severely ill and had been hospitalized longer than fullterm NICU children, were more likely to engage in solicitous pain-related behavior. Maternal influence was also assessed by comparing heat pain thresholds and perceptual sensitization to tonic painful heat obtained in the presence versus absence (i.e. standard testing conditions) of the mother. In all three groups, maternal presence was associated with increased heat pain thresholds. Control children habituated significantly more to tonic heat when their mother was present. The NICU children showed overall significantly less habituation than the controls; there was no modulating effect of maternal presence. Especially in highly vulnerable children such as preterms, neonatal pain exposure and prolonged hospitalization may, aside from neuronal plasticity, promote maladaptive pain-related cognitions and foster parental behavior that reinforces the child's pain response.

Dimensions of pain-related parent behavior: development and psychometric evaluation of a new measure for children and their parents.

The development and maintenance of chronic pain are influenced by its social context, and especially by the responses of family members. For children, very few instruments are available that measure pain-related parental behavior. Using the Multidimensional Pain Inventory for adults (MPI; [Kerns RD, Turk DC, Rudy TE. The west haven-yale multidimensional pain inventory (WHYMPI). Pain 1985;23:345-356.]) as a model, we developed and evaluated a child and parent versions of the Pain-related Parent Behavior Inventory (PPBI). Here, we specifically studied maternal pain-related behavior as perceived by the child and self-reported by the mother. As substantiated by exploratory factor analysis in a mixed sample of 193 children and adolescents (8-16 years) either suffering from recurrent pain of different origin or being healthy controls, both PPBI versions entail the identical subscale solicitousness, distracting behaviors and discouraging/ignoring responses. Child and parent PPBI subscales were internally consistent and were not substantially related to age or gender. Validity analyses yielded a pattern of correlations with measures of depression, trait anxiety, pain activity, and pain-related cognitions that is consistent with the psychometric data for the adult MPI and findings on the social context of chronic pain. Child-perceived maternal behavior was significantly related to overall parenting and to mothers' actual behavior as observed during a cold pressor test. Finally, the PPBI was sensitive to differences in mothers' responses depending on the specific nature of the child's pain. Child and parent reports of parental behaviors were modestly correlated and were differentially related to the validity measures, hence supporting the importance of assessing the social context of pediatric pain independently of both the child's and the parent's perspectives.

Somatic pain sensitivity in children with recurrent abdominal pain.

OBJECTIVE: Evidence is accumulating that recurrent abdominal pain (RAP) in children is associated with visceral hyperalgesia. However, it is not known whether somatic sensitivity is altered as well. Therefore, the aim of our study was to assess somatic pain sensitivity in children with RAP and healthy controls at the abdomen and a distal site (thenar). METHODS: We examined 20 children with RAP (age 8-14) and 23 healthy control children (age 9-14). Heat and mechanical pain thresholds as well as measures of perceptual sensitization in response to repetitive mechanical or tonic thermal noxious stimulation were assessed. RESULTS: At the abdominal site, pain sensitivity in children with RAP did not differ significantly when compared to controls. At the thenar, pain thresholds of children in the RAP group were not significantly different from control children. However, children with RAP showed less perceptual sensitization in response to tonic heat and repetitive mechanical stimuli (ps

Altered pain processing in children with migraine: an evoked potential study.

In adults, evidence is accumulating that migraine is associated with altered central processing of pain stimuli and, possibly, changes in the allocation of attentional resources to such stimuli. In pediatric migraine, however, little is known about altered pain processing. We examined 15 children with migraine and 15 controls (age 10-15) in an oddball standards task. Children had to respond to rare targets (tones) and ignore frequent painful (pain threshold) or non-painful mechanical standard stimuli while evoked potentials were obtained. Painful as compared to non-painful stimuli elicited significantly larger N150, P260 and P300 components of the somatosensory evoked potential in all children. The pain-evoked N150 and P260 components did not differ significantly between groups. However, in children with migraine, both painful and non-painful standard stimuli were associated with significantly larger P300 amplitudes at significantly shorter latencies. Perceived intensity of the painful and non-painful stimuli was comparable in both groups. The evoked potentials and reaction times to the target tones did not differ significantly between groups. Habituation across trials was similar in both groups. Hence, children with migraine may display an automatic attentional bias towards painful and potentially painful somatosensory stimuli. Consistent with the psychobiological perspective of chronic pain, such an attentional bias could constitute an important mechanism for migraine becoming a chronic problem.

Cortical correlates of an attentional bias to painful and innocuous somatic stimuli in children with recurrent abdominal pain.

Recurrent abdominal pain (RAP) is a common gastrointestinal problem during childhood. It is not only a pediatric health problem, but may represent a risk factor for chronic pain, psychosomatic symptoms, and psychopathological problems later in life. Alterations in central pain processing and an attentional bias to potentially aversive somatic sensations could contribute to the unfavorable outcome of RAP during childhood. Fourteen children with RAP and 15 control children (age: 10-15 year) participated in an attentional task. Children had to respond to rare targets (tones) and ignore frequent either painful (pain threshold) or non-painful mechanical stimuli delivered at the hand. Event-related cortical potentials in response to the somatic stimuli and the tones were measured and stimulus intensity ratings, reaction time and number of errors were obtained. Painful as compared to non-painful stimuli elicited significantly larger N1, P2 and P3 components of the somatosensory-evoked potential (SEP) in all children. The RAP children responded with a significantly larger P3 to both painful and non-painful stimuli. No group differences were found for the auditory-evoked potentials. Perceived stimulus and pain intensity, reaction time and number of errors did not differ between groups. Similar to findings in adults with functional gastrointestinal disorders (FGIDs), children with RAP did not show somatic hyperalgesia as revealed by unaltered pain thresholds and middle latency pain-evoked SEPs. However, they displayed an attentional bias to painful and non-painful (innocuous) somatic stimuli as indicated by an enhanced P3. This may represent an important mechanism not only for the maintenance of RAP, but also for the development of psychosomatic symptoms.

The impact of chronic pain in children and adolescents: Development and initial validation of a child and parent version of the Pain Experience Questionnaire.

Psychosocial factors are crucial for understanding and treating chronic pain in adults, but also in children. For children, very few questionnaires for a multidimensional pain assessment exist. In adults, the Multidimensional Pain Inventory (MPI; [Kerns RD, Turk DC, Rudy TE. The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain 1985;23:345-56]) has been widely used to determine patients' adjustment to chronic pain. Using one section of the MPI as a model, we developed and evaluated the Pain Experience Questionnaire (PEQ) - child and parent version - that assesses the psychosocial impact of chronic pain in children and adolescents. As substantiated by confirmatory factor analysis in a sample of 111 children and adolescents (7-18 years) with chronic pain, the child PEQ entails the subscales pain severity, pain-related interference, affective distress and perceived social support. The parent version contains the subscales severity of the child's pain, interference and parental affective distress. Child and parent PEQ subscales were internally consistent. Age was unrelated to PEQ subscale scores. Girls and their mothers endorsed significantly greater pain severity, interference and affective distress. Validity analyses yielded a pattern of correlations with measures of depression, trait anxiety, pain activity, child behaviors, pain-related cognitions, and parenting behavior that is consistent with psychometric data of the adult MPI and previous findings on psychosocial aspects of chronic pediatric pain. Significant differences between children depending on patient status (participants in experimental or treatment studies, outpatients, inpatients) suggest external validity of the PEQ. Despite the preliminary nature of the psychometric evaluation, the child and parent PEQ seem promising for a comprehensive assessment of pediatric pain.

The assessment of pain coping and pain-related cognitions in children and adolescents: current methods and further development.

UNLABELLED: Pain coping and pain-related cognitions are considered important for the understanding of chronic pain in children. Based on a systematic literature search, 4 instruments were identified that assess a range of pain coping strategies and one questionnaire focusing on pain-related cognitions. Three of these tools have good psychometric quality. Yet, only the Pain Coping Questionnaire (PCQ) has been widely used across different pain conditions and by several international research groups. We designed the Pain-Related Cognitions Questionnaire for Children (PRCQ-C) as an abbreviated German version of the PCQ. Factorial, construct, and external validity were tested in a sample of 401 children and adolescents (7-18 years) comprising 253 school children and 148 children having recurrent pain. The proposed 3 subscales, "catastrophizing," "problem-solving," and "positive self-statements," were confirmed, all having good internal consistency and retest reliability. No age and only marginal gender differences were observed. Catastrophizing was associated with dysphoric mood, trait anxiety, and current pain activity. Subgroups of pain patients differed with regard to catastrophizing and positive self-statements. PERSPECTIVE: The PRCQ-C is a brief instrument for the assessment of pain-related cognitions in children and adolescents. It supports the validity of the PCQ, demonstrates its use in an abbreviated version and extends its international availability.

Long-term alteration of pain sensitivity in school-aged children with early pain experiences.

While animal studies suggest that neonatal pain experiences induce long-term alterations in pain sensitivity, no such data exist in humans. Changes in pain sensitivity in school-aged children (9-14 years) who were born preterm or fullterm, had been hospitalized for a prolonged period of time after birth and had undergone repeated painful procedures while being treated in a Neonatal Intensive Care Unit (NICU) were determined. A retrospective cohort study of 19 preterm (or=37 weeks gestational age) treated at least 3 days in a NICU at a University Hospital and 20 fullterm control children without NICU experience was performed. Perceptual sensitization to tonic heat and repetitive mechanical stimuli as well as heat pain and mechanical pain thresholds were obtained at the thenar and a trigeminal site. Length of hospitalization and NICU treatment was significantly higher in preterm than fullterm children. Nonetheless, both preterm and fullterm children with NICU experience showed greater perceptual sensitization to tonic heat and elevated heat pain thresholds at both sites. Mechanical pain threshold and perceptual sensitization did not differ between groups. Consistent with findings in animals, repeated pain experiences during the neonatal period were associated with alterations in thermal pain responsivity in school-aged preterm and fullterm children that was characterized by enhanced perceptual sensitization to prolonged painful stimulation and hypoalgesia to brief heat pain stimuli. Our findings suggest that repeated pain experiences in neonates may induce activity-induced changes in the functioning of pain pathways that persist well beyond infancy.

Quantitative sensory testing in children with migraine: preliminary evidence for enhanced sensitivity to painful stimuli especially in girls.

Recent studies showed an enhanced general sensitivity to painful stimuli in adult migraineurs during as well as between attacks. Yet, the influence of a prolonged pain history and potential sex differences has not been studied. We used quantitative sensory testing to examine 25 children with migraine between attacks and 28 controls (age 9-15). The assessment included the measurement of heat and mechanical pain thresholds as well as measures of perceptual sensitization in response to repetitive (mechanical) or tonic (thermal) noxious stimulation at both trigeminal and thenar sites. In addition, the mother was either present or absent during the measurements. Heat pain thresholds were not significantly different between the two groups. However, the child migraineurs showed significantly lower mechanical pain thresholds. Children and especially girls with migraine displayed significantly more sensitization to a tonic heat stimulus at the trigeminal site when the mother was present. The migraineurs also showed a trend towards higher sensitization ratings for mechanical stimuli. Overall, heat pain thresholds were significantly higher in the presence of the mother. In the migraine group only, mechanical pain thresholds were significantly higher when the mother was present. To summarize, an enhanced sensitivity to painful stimuli can already be observed in children suffering from migraine for an average duration of 4.4 years. This may be the result of sensitization in nociceptive pain pathways caused by frequent pain experiences. Girls with migraine were more prone to such sensitization, which may increase their risk for continuing to suffer from migraine throughout adulthood.