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

Wollgarten-Hadamek, Iris; Hohmeister, Johanna; Zohsel, Katrin; Flor, Herta; Hermann, Christiane

doi:10.1016/j.ejpain.2010.09.001

Cited by 23 publications

(18 citation statements)

References 61 publications

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“…Furthermore, our observed impairment is consistent with clinical reports of attenuated stress-induced analgesia in adolescents and teens that experienced burns early in infancy [9]. Consistent with our observed increase in endogenous opioid tone, high levels of enkephalin are known to dampen the perception of noxious or aversive stimuli, including pain associated with formalin inflammation, anxiety in the elevated plus maze and fecal boluses excreted in response to immobilization stress [50,53,54].…”

Section: Discussionsupporting

confidence: 90%

“…Despite strong evidence that pain and stress circuitry are established and functional in preterm infants, 65% of these procedures are performed in the complete absence of analgesics [3,4,5,6,7]. Unfortunately, it is becoming increasingly clear that pain experienced during the critical perinatal developmental period has long-lasting effects on adult responses to pain-, anxiety- and stress-provoking stimuli [8,9,10]. …”

Section: Introductionmentioning

confidence: 99%

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A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

Victoria

Inoue²,

Young³

et al. 2013

Dev Neurosci

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Approximately 500,000 infants are born prematurely each year in the United States. These infants typically require an extensive stay in the neonatal intensive care unit (NICU), where they experience on average 14 painful and invasive procedures each day. These procedures, including repeated heel lance, insertion of intravenous lines, and respiratory and gastric suctioning, typically result in an inflammatory response, inducing pain and stress in the newborn. Remarkably, the majority of these procedures are performed in the complete absence of pre- or post-emptive analgesics. Recent clinical studies report that former NICU patients have increased thresholds for pain and stress later in life as compared with term-born infants. However, to date, the mechanisms whereby early-life inflammation alters later-life response to stress and pain are not known. The present studies were conducted to determine if neonatal injury impairs adult responses to anxiety- and stress-provoking stimuli. As we have previously reported that early-life pain results in a significant increase in opioid peptide expression within the midbrain periaqueductal gray, the role of endogenous opioids in our behavioral studies was also examined. Male and female rats received an intraplantar injection of the inflammatory agent carrageenan (1%) on the day of birth. In adulthood, animals were assessed for changes in response to anxiety- and stress-provoking stimuli using the open field and forced swim tests, respectively. Injury-induced changes in sucrose preference and stress-induced analgesia were also assessed. As adults, neonatally injured animals displayed a blunted response to both anxiety- and stress-provoking stimuli, as indicated by significantly more time spent in the inner area of the open field and a 2-fold increase in latency to immobility in the forced swim test as compared to controls. No change in sucrose preference was observed. Using in situ hybridization and immunohistochemistry, we observed a 2-fold increase in enkephalin mRNA and protein expression, respectively, in stress-related brain regions including the central amygdala and lateral septum. Administration of the opioid receptor antagonist naloxone reversed the attenuated responses to forced swim stress and stress-induced analgesia, suggesting the changes in stress-related behavior were opioid-dependent. Together, these data contribute to mounting evidence that neonatal injury in the absence of analgesics has adverse effects that are both long-term and polysystemic.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

Victoria

Inoue²,

Young³

et al. 2013

Dev Neurosci

View full text Add to dashboard Cite

show abstract

“…Tables 1 through 4 provide the results of the systematic review separately by experimental pain induction method. Note that the following studies eligible for inclusion in the systematic review conducted additional experimental pain tasks (e.g., fabric prickliness test, ischemic pain, brush allodynia, manual palpation, dynamic mechanical allodynia, tactile pain sensitivity) but did not conduct statistical tests examining sex differences in healthy children and therefore are not included in Tables 1-4: [ 6,18,49,89,111,115].Pain intensity. Of the pain tasks where it was reported that statistical tests of sex differences in pain intensity were conducted (n=21 pain tasks from 18 unique studies), 90.5%…”

mentioning

confidence: 99%

Sex differences in experimental pain among healthy children: A systematic review and meta-analysis

Boerner

Birnie

Caes

et al. 2014

Pain

108

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Sex differences in response to experimental pain are commonly reported in systematic reviews in the adult literature. The objective of the present research was to conduct a systematic review and meta-analysis of sex differences in healthy children's responses to experimental pain (e.g., cold pressor, heat pain, pressure pain) and, where possible, to conduct analyses separately for children and adolescents. A search was conducted of electronic databases for published papers in English of empirical research using experimental pain tasks to examine pain-related outcomes in healthy boys and girls between 0 and 18 years of age. Eighty articles were eligible for inclusion and were coded to extract information relevant to sex differences. The systematic review indicated that, across different experimental pain tasks, the majority of studies reported no significant differences between boys and girls on painrelated outcomes. However, the meta-analysis of available combined data found that girls reported significantly higher pain intensity compared to boys in studies where the mean age of participants was greater than 12 years. Additionally, a meta-analysis of heat pain found that boys had significiantly higher tolerance than girls overall, and boys had significantly higher heat pain threshold than girls in studies where the mean age of participants was 12 years or younger. These findings suggest that developmental stage may be relevant for understanding sex differences in pain . 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 SEX DIFFERENCES IN EXPERIMENTAL PAIN IN CHILDREN AbstractSex differences in response to experimental pain are commonly reported in systematic reviews in the adult literature. The objective of the present research was to conduct a systematic review and meta-analysis of sex differences in healthy children's responses to experimental pain (e.g., cold pressor, heat pain, pressure pain) and, where possible, to conduct analyses separately for children and adolescents. A search was conducted of electronic databases for published papers in English of empirical research using experimental pain tasks to examine pain-related outcomes in healthy boys and girls between 0 and 18 years of age. Eighty articles were eligible for inclusion and were coded to extract information relevant to sex differences. The systematic review indicated that, across different experimental pain tasks, the majority of studies reported no significant differences between boys and girls on pain-related outcomes. However, the meta-analysis of available combined data found that girls reported significantly higher pain intensity compared to boys in studies where the mean age of participants was greater than 12 years. Additionally, a meta-analysis of heat pain found that boys had significiantly higher tolerance than girls overall, and...

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“…For example, children, teens and young adults born prematurely are rated as less sensitive to pain by their parents and physicians [15,[46][47][48] , display reduced stressinduced analgesia [49] and show blunted cortisol reactivity to psychological stress testing [50] . In contrast, a hyperalgesic response is observed in these children following surgery in the same dermatome, which is accompanied by increased negative verbalizations and a higher incidence of catastrophic, rather than solution-based, thoughts related to painful interventions [51][52][53] .…”

Section: Morphine Treatment Rescues Stress Coping Following Chronic Smentioning

confidence: 99%

Analgesia for Early-Life Pain Prevents Deficits in Adult Anxiety and Stress in Rats

2014

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Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this ‘hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a ‘hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants.

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

Cited by 23 publications

References 61 publications

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

A Single Neonatal Injury Induces Life-Long Deficits in Response to Stress

Sex differences in experimental pain among healthy children: A systematic review and meta-analysis

Analgesia for Early-Life Pain Prevents Deficits in Adult Anxiety and Stress in Rats

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