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Published on: January 25, 2016
Neonatal Sleep Restriction Increases Nociceptive Sensitivity in Adolescent Mice
Paula Araujo1, Cesar A Coelho1, Maria G Oliveira1
1Departamento de Psicobiologia, Universidade Federal de São Paulo (UNIFESP), Brazil.
Insights
Neonatal sleep restriction in mice led to increased pain sensitivity in adolescence, linked to altered neuronal activity in the periaqueductal gray. This hypersensitivity resolved by adulthood, suggesting early life sleep loss impacts pain pathways during development.
Area of Science:
- Neuroscience
- Developmental Biology
- Sleep Science
Background:
- Infant sleep loss may negatively impact the developing nociceptive system.
- Neonatal sleep restriction is hypothesized to cause long-term increases in pain behaviors and alter nociceptive pathway neuronal activity.
Purpose of the Study:
- Investigate the long-term effects of neonatal sleep loss on pain behaviors in adolescent and adult mice, considering sex differences.
- Analyze neuroanatomical and functional changes in pain pathways related to observed behavioral alterations.
Main Methods:
- Neonatal mice (postnatal day 12) underwent sleep restriction (SR) or maternal separation (MS) for 10 days.
- Pain behaviors were assessed at postnatal days 21, 35, and 90.
- Immunohistochemistry for c-Fos protein was performed in key brain regions, including the periaqueductal gray (PAG).
Main Results:
- Neonatal SR significantly increased nociceptive sensitivity in adolescent mice (hot plate test).
- This hypersensitivity correlated with decreased c-Fos expression in the PAG.
- Pain hypersensitivity was absent in adult mice, indicating a transient effect.
Conclusions:
- Repeated early-life sleep loss can alter nociceptive responses.
- These changes are associated with modifications in the neural activity of descending pain control pathways.
- The findings highlight the critical role of early sleep in pain system development.
Background:
Sleep loss in infants may have a negative effect on the functional and structural development of the nociceptive system. We tested the hypothesis that neonatal sleep restriction induces a long-term increase of pain-related behaviors in mice and that this hypersensitivity occurs due to changes in the neuronal activity of nociceptive pathways.
Objectives:
We aim to investigate the effects of sleep loss in neonatal mice on pain behaviors of adolescent and adult mice in a sex-dependent manner. We also analyzed neuroanatomical and functional changes in pain pathways associated with behavioral changes.
Study Design:
An experimental animal study.
Setting:
A basic sleep research laboratory at Universidade Federal de São Paulo in Brazil.
Methods:
Neonatal mice at postnatal day (PND) 12 were randomly assigned to either control (CTRL), maternal separation (MS), or sleep restriction (SR) groups. MS and SR were performed 2 hours a day for 10 days (PND 12 until PND 21). The gentle handling method was used to prevent sleep. At PND 21, PND 35, or PND 90, the mice were tested for pain-related behaviors. Their brains were harvested and immunohistochemically stained for c-Fos protein in the anterior cingulate cortex, primary somatosensory cortex, and periaqueductal gray (PAG).
Results:
Neonatal SR significantly increased nociceptive sensitivity in the hot plate test in adolescent mice (-23.5% of pain threshold). This alteration in nociceptive response was accompanied by a decrease in c-Fos expression in PAG (-40% of c-Fos positive cells compared to the CTRL group). The hypersensitivity found in adolescent mice was not present in adult animals, and all mice showed a comparable nociceptive response.
Limitations:
Even using a mild manipulation method, in which a minimal amount of handling was applied to maintain wakefulness, sleep deprivation was a stressful event evidenced by higher corticosterone levels.
Conclusion:
Repeated exposures to sleep loss during early life were able to induce changes in the nociceptive response associated with alterations in neural activity in descending control of pain.
Key Words:
Brain maturation, hypersensitivity, neuronal activity, nociception, pain, periaqueductal gray, postnatal development, sleep, sleep deprivation.
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