Neuroscience Institute, Center for Behavioral Neuroscience, Georgia State University, Atlanta, Georgia, 30303.
Dev Neurobiol. 2014 Jan;74(1):42-51. doi: 10.1002/dneu.22129. Epub 2013 Oct 17.
Less than 60% of infants undergoing invasive procedures in the neonatal intensive care unit receive analgesic therapy. These infants show long-term decreases in pain sensitivity and cortisol reactivity. In rats, we have previously shown that inflammatory pain experienced on the day of birth significantly decreases adult somatosensory thresholds and responses to anxiety- and stress-provoking stimuli. These long-term changes in pain and stress responsiveness are accompanied by two-fold increases in central met-enkephalin and β-endorphin expression. However, the time course over which these changes in central opioid peptide expression occur, relative to the time of injury, are not known. The present studies were conducted to determine whether the observed changes in adult opioid peptide expression were present within the first postnatal week following injury. The impact of neonatal inflammation on plasma corticosterone, a marker for stress reactivity, was also determined. Brain, spinal cord, and trunk blood were harvested at 24 h, 48 h, and 7 d following intraplantar administration of the inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to determine plasma corticosterone and met-enkephalin and β-endorphin levels within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury, met-enkephalin levels were significantly increased in the midbrain, but decreased in the spinal cord and cortex; forebrain β-endorphin levels were significantly increased as a result of early life pain. Corticosterone levels were also significantly increased. At 7 d post-injury, opioid peptides remained elevated relative to controls, suggesting a time point by which injury-induced changes become programmed and permanent.
在新生儿重症监护病房接受有创操作的婴儿中，不到 60%接受了镇痛治疗。这些婴儿表现出长期的疼痛敏感性和皮质醇反应性下降。在大鼠中，我们之前已经表明，出生当天经历的炎症性疼痛会显著降低成年后的体感阈值，并对焦虑和应激性刺激做出反应。这些疼痛和应激反应的长期变化伴随着中枢内啡肽和β-内啡肽表达增加一倍。然而，中枢阿片肽表达的这些变化相对于损伤发生的时间进程尚不清楚。本研究旨在确定在损伤后第一周内，成年阿片肽表达的这些变化是否存在。还确定了新生儿炎症对血浆皮质酮（应激反应的标志物）的影响。在出生当天足底注射炎症剂角叉菜胶后 24 h、48 h 和 7 d 时，收获大脑、脊髓和躯干血液。放射免疫测定法用于测定大脑前区、皮质、中脑和脊髓中的血浆皮质酮和内啡肽和β-内啡肽水平。在损伤后 24 h 内，中脑中的内啡肽水平显著增加，但脊髓和皮质中的内啡肽水平降低；由于早期生命疼痛，前脑中的β-内啡肽水平显著增加。皮质酮水平也显著增加。在损伤后 7 天，与对照组相比，阿片肽仍处于升高状态，这表明损伤诱导的变化成为编程和永久性的时间点。
