Effects of opiates on neuronal development in the rat cerebral cortex

doi:10.1016/0361-9230(93)90078-P

Brain Research Bulletin

Volume 30, Issues 5–6, 1993, Pages 523-527

https://doi.org/10.1016/0361-9230(93)90078-P Get rights and content

Abstract

Quantitative morphological characteristics of cells in the primary somatosensory cortex of 6-dayold rats were examined following continuous maternal administration of morphine (10 mg/kg/day), naltrexone (10 mg/kg/day), or saline vehicle from gestation day 12. Naltrexone reduced neuronal packing density and significantly increased cortical thickness but had no effect on neuronal number, while morphine reduced neuronal packing density and the number of neurons without affecting cortical thickness. These results suggest that blockade of endogenous opioid function during development enhances neuronal maturation in this brain region, while perinatal morphine administration might act to restrict cortical cell proliferation and maturation. Thus, the effect of ontogenetic activation of opioid receptors by endogenous opioid compounds could be similar to but less severe than the effect of exogenous opiate exposure on cortical cell development.

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The consequences of neonatal pain, stress and opiate administration in animal models: An extensive meta-analysis concerning neuronal cell death, motor and behavioral outcomes
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Citation Excerpt :
Moreover, concerns regarding the safety of opiates, which are first line medication for the management of pain and discomfort in preterm and term infants, have also been raised. There is evidence suggesting that early opiate exposure in rodents results in behavioral and motor difficulties (Handelmann and Dow-Edwards, 1985), altered dendritic architecture, and increased neuronal apoptosis (Bajic et al., 2013; Hammer et al., 1989; Seatriz and Hammer, 1993). However, it has been also documented that adequate administration of morphine, given prior to a painful procedure in rats, has a neuro-protective effect (Duhrsen et al., 2013).
This systematic review and meta-analysis aimed to investigate the association of neonatal exposure to pain, stress, opiate administration alone, as well as opiate administration prior to a painful procedure on neuronal cell death, motor, and behavioral outcomes in rodents. In total, 36 studies investigating the effect of pain (n = 18), stress (n = 15), opiate administration (n = 13), as well as opiate administration prior to a painful event (n = 7) in rodents were included in our meta-analysis. The results showed a large effect of pain (g = 1.37, 95% CI 1.00–1.74, p < .001) on neuronal cell death. Moreover, higher number of neonatal pain events were significantly associated with increased neuronal cell death, increased anxiety (b = −1.18, SE = 0.43, p = .006), and depressant-like behavior (b = 1.74, SE = 0.51, p = .027) in rodents. Both opiates and pain had no impact on motor function (g = 0.26, 95% CI 0.18–0.70, p = .248).
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Relief of human suffering is one of the most important goals of all healthcare providers. Advances in neonatology have significantly reduced neonatal morbidity and mortality, but pain, discomfort, and stress remain sad realities for babies in the neonatal intensive care unit (NICU). Assessing, managing, and trying to limit these clinical realities, particularly while caring for critically ill neonates, remain challenging and increasingly controversial. Fortunately, considerable clinical and laboratory research and clinical dialogue continue to push neonatal providers toward best clinical practices in this problematic arena. This chapter describes the history, developmental biology, and public policies that have informed and shaped current clinical practices; it also summarizes relevant clinical and basic research regarding clinical assessment tools and both pharmacologic and nonphar¬macologic management approaches. Finally, future directions in this field are suggested.
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Optimal obstetric and neonatal care requires the provision of adequate analgesia for painful procedures. However, anesthetic and analgesic agents have the potential to adversely impact the developing fetal/neonatal brain. In this setting, clinicians must assess the risks and benefits of pharmacologic anesthesia and analgesia for specific indications in this population. General anesthesia is required for non-obstetric surgery and cesarean section in the absence of neuraxial anesthesia for the health of the mother and fetus. Although experimental data raise concerns, human data are reassuring and future research may focus on neuroprotective adjuncts in the setting of repeated or prolonged anesthetic exposures. Opioid analgesia is standard of care for preterm infants undergoing major procedures including invasive surgery and endotracheal intubation. The use of opioids for agitation resulting from mechanical ventilation is controversial, but prevalent. Randomized and retrospective studies detect short-term toxicity with inconclusive long-term impact, suggesting the need to explore alternative therapies.
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Impaired neurodevelopmental outcomes in very preterm infants: Much too easy to blame it just on morphine!
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ArticleEffects of opiates on neuronal development in the rat cerebral cortex

Abstract

Eur. J. Pharmacol.

Dev. Brain Res.

Dev. Brain Res.

Int. J. Dev. Neurosci.

Dev. Brain Res.

Life Sci.

Dev. Brain Res.

Brain Res.

Life Sci.

Life Sci.

Dev. Brain Res.

Brain Res.

Article
Effects of opiates on neuronal development in the rat cerebral cortex