The Neurodevelopmental Impact of Neonatal Morphine Administration

Overview

Journal Brain Sci

Publisher MDPI

Date 2014 Jun 26

PMID 24961764

Citations 31

Authors

Stephanie Attarian

Lan Chi Tran

Aimee Moore

George Stanton

Eric Meyer

Robert P Moore

Affiliations

Soon will be listed here.

Abstract

Medical management of newborn infants often necessitates recurrent painful procedures, which may alter nociceptive pathways during a critical developmental period and adversely effect neuropsychological outcomes. To mitigate the effects of repeated painful stimuli, opioid administration for peri-procedural analgesia and ICU (intensive care unit) sedation is common in the NICU (neonatal intensive care unit). A growing body of basic and animal evidence suggests potential long-term harm associated with neonatal opioid therapy. Morphine increases apoptosis in human microglial cells, and animal studies demonstrate long-term changes in behavior, brain function, and spatial recognition memory following morphine exposure. This comprehensive review examines existing preclinical and clinical evidence on the long-term impacts of neonatal pain and opioid therapy.

Citing Articles

Improved Post-Operative Outcomes and Reduced Narcotic Use With ERAS Protocol in a Pediatric Ambulatory Surgery Setting.

Singh N, Ahn J, Chen X, Park S, Singh S, Cardamone S Paediatr Neonatal Pain. 2025; 7(1):e70004.

PMID: 40066436 PMC: 11891489. DOI: 10.1002/pne2.70004.

The effect of using dexmedetomidine versus morphine as sedation on long-term neurodevelopmental outcomes of encephalopathic neonates undergoing therapeutic hypothermia.

Nuzum T, Kazmi S, Wachtel E J Perinatol. 2025; .

PMID: 39979431 DOI: 10.1038/s41372-025-02227-y.

Repetitive daily oxytocin treatment reduces weight gain but not acute neonatal procedural pain.

Baudat M, Joosten E, Simons S Pediatr Res. 2024; .

PMID: 39523390 DOI: 10.1038/s41390-024-03680-9.

Oral Clonidine-Based Strategy to Reduce Opiate Use During Cooling for Neonatal Encephalopathy: An Observational Study.

Fribance H, Liang C, Lee C, Aziz K, Parkinson C, Gauda E J Pediatr. 2024; 273:114158.

PMID: 38889855 PMC: 11415280. DOI: 10.1016/j.jpeds.2024.114158.

Treatment for Neonatal Abstinence Syndrome Using Nonpharmacological Interventions.

Robinson T, Stikes R, Sorrell J, Gater A, Booth A, Gardner A Am J Perinatol. 2024; 41(16):2198-2205.

PMID: 38729163 PMC: 11534461. DOI: 10.1055/s-0044-1786744.

References

Maxwell L, Malavolta C, Fraga M . Assessment of pain in the neonate. Clin Perinatol. 2013; 40(3):457-69. DOI: 10.1016/j.clp.2013.05.001. View

Roofthooft D, Simons S, Anand K, Tibboel D, Dijk M . Eight years later, are we still hurting newborn infants?. Neonatology. 2014; 105(3):218-26. DOI: 10.1159/000357207. View

McPherson C . Sedation and analgesia in mechanically ventilated preterm neonates: continue standard of care or experiment?. J Pediatr Pharmacol Ther. 2013; 17(4):351-64. PMC: 3567888. DOI: 10.5863/1551-6776-17.4.351. View

Handelmann G, Dow-Edwards D . Modulation of brain development by morphine: effects on central motor systems and behavior. Peptides. 1985; 6 Suppl 2:29-34. DOI: 10.1016/0196-9781(85)90131-7. View

Duhrsen L, Simons S, Dzietko M, Genz K, Bendix I, Boos V . Effects of repetitive exposure to pain and morphine treatment on the neonatal rat brain. Neonatology. 2012; 103(1):35-43. DOI: 10.1159/000341769. View

de Graaf J, van Lingen R, Simons S, Anand K, Duivenvoorden H, Weisglas-Kuperus N . Long-term effects of routine morphine infusion in mechanically ventilated neonates on children's functioning: five-year follow-up of a randomized controlled trial. Pain. 2011; 152(6):1391-1397. DOI: 10.1016/j.pain.2011.02.017. View

Anand K . Clinical importance of pain and stress in preterm neonates. Biol Neonate. 1998; 73(1):1-9. DOI: 10.1159/000013953. View

Simons S, Dijk M, Anand K, Roofthooft D, van Lingen R, Tibboel D . Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates. Arch Pediatr Adolesc Med. 2003; 157(11):1058-64. DOI: 10.1001/archpedi.157.11.1058. View

Anand K, Hickey P . Pain and its effects in the human neonate and fetus. N Engl J Med. 1987; 317(21):1321-9. DOI: 10.1056/NEJM198711193172105. View

10.

Franz A, Pohlandt F, Bode H, Mihatsch W, Sander S, Kron M . Intrauterine, early neonatal, and postdischarge growth and neurodevelopmental outcome at 5.4 years in extremely preterm infants after intensive neonatal nutritional support. Pediatrics. 2009; 123(1):e101-9. DOI: 10.1542/peds.2008-1352. View

11.

Juul S, Beyer R, Bammler T, Farin F, Gleason C . Effects of neonatal stress and morphine on murine hippocampal gene expression. Pediatr Res. 2010; 69(4):285-92. PMC: 3085998. DOI: 10.1203/PDR.0b013e31820bd165. View

12.

Ruda M, Ling Q, Hohmann A, Peng Y, Tachibana T . Altered nociceptive neuronal circuits after neonatal peripheral inflammation. Science. 2000; 289(5479):628-31. DOI: 10.1126/science.289.5479.628. View

13.

Katebi S, Razavi Y, Alamdary S, Khodagholi F, Haghparast A . Morphine could increase apoptotic factors in the nucleus accumbens and prefrontal cortex of rat brain's reward circuitry. Brain Res. 2013; 1540:1-8. DOI: 10.1016/j.brainres.2013.09.045. View

14.

Zhang Y, Chen Q, Yu L . Morphine: a protective or destructive role in neurons?. Neuroscientist. 2008; 14(6):561-70. DOI: 10.1177/1073858408314434. View

15.

Boronat M, Garcia-Fuster M, Garcia-Sevilla J . Chronic morphine induces up-regulation of the pro-apoptotic Fas receptor and down-regulation of the anti-apoptotic Bcl-2 oncoprotein in rat brain. Br J Pharmacol. 2001; 134(6):1263-70. PMC: 1573055. DOI: 10.1038/sj.bjp.0704364. View

16.

Simons S, Dijk M, van Lingen R, Roofthooft D, Duivenvoorden H, Jongeneel N . Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial. JAMA. 2003; 290(18):2419-27. DOI: 10.1001/jama.290.18.2419. View

17.

Fitzgerald M, Millard C, McIntosh N . Cutaneous hypersensitivity following peripheral tissue damage in newborn infants and its reversal with topical anaesthesia. Pain. 1989; 39(1):31-36. DOI: 10.1016/0304-3959(89)90172-3. View

18.

Bajic D, Commons K, Soriano S . Morphine-enhanced apoptosis in selective brain regions of neonatal rats. Int J Dev Neurosci. 2013; 31(4):258-66. PMC: 3640697. DOI: 10.1016/j.ijdevneu.2013.02.009. View

19.

Bouza H . The impact of pain in the immature brain. J Matern Fetal Neonatal Med. 2009; 22(9):722-32. DOI: 10.3109/14767050902926962. View

20.

Fitzgerald M, Beggs S . The neurobiology of pain: developmental aspects. Neuroscientist. 2001; 7(3):246-57. DOI: 10.1177/107385840100700309. View