Early Repetitive Pain in Preterm Infants in Relation to the Developing Brain

Overview

Journal Pain Manag

Specialty Psychiatry

Date 2014 Mar 20

PMID 24641344

Citations 86

Authors

Manon Ranger

Ruth E Grunau

Affiliations

Soon will be listed here.

Abstract

Infants born preterm (<37 weeks of gestation) are particularly vulnerable to procedural stress and pain exposure during neonatal intensive care, at a time of rapid and complex brain development. Concerns regarding effects of neonatal pain on brain development have long been expressed. However, empirical evidence of adverse associations is relatively recent. Thus, many questions remain to be answered. This review discusses the short- and long-term effects of pain-related stress and associated treatments on brain maturation and neurodevelopmental outcomes in children born preterm. The current state of the evidence is presented and future research directions are proposed.

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References

Johnston C, Barrington K, Taddio A, Carbajal R, Filion F . Pain in Canadian NICUs: have we improved over the past 12 years?. Clin J Pain. 2010; 27(3):225-32. DOI: 10.1097/AJP.0b013e3181fe14cf. View

Blencowe H, Cousens S, Oestergaard M, Chou D, Moller A, Narwal R . National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet. 2012; 379(9832):2162-72. DOI: 10.1016/S0140-6736(12)60820-4. View

Johnston C, Filion F, Snider L, Majnemer A, Limperopoulos C, Walker C . Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks' postconceptional age. Pediatrics. 2002; 110(3):523-8. DOI: 10.1542/peds.110.3.523. View

Spittle A, Treyvaud K, Doyle L, Roberts G, Lee K, Inder T . Early emergence of behavior and social-emotional problems in very preterm infants. J Am Acad Child Adolesc Psychiatry. 2009; 48(9):909-918. DOI: 10.1097/CHI.0b013e3181af8235. View

Miller S, Vigneron D, Henry R, Bohland M, Ceppi-Cozzio C, Hoffman C . Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury. J Magn Reson Imaging. 2002; 16(6):621-32. DOI: 10.1002/jmri.10205. 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, Coskun V, Thrivikraman K, Nemeroff C, Plotsky P . Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav. 1999; 66(4):627-37. PMC: 4211637. DOI: 10.1016/s0031-9384(98)00338-2. View

Volpe J . Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2008; 8(1):110-24. PMC: 2707149. DOI: 10.1016/S1474-4422(08)70294-1. View

Carbajal R, Rousset A, Danan C, Coquery S, Nolent P, Ducrocq S . Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA. 2008; 300(1):60-70. DOI: 10.1001/jama.300.1.60. View

10.

Low L, Fitzgerald M . Acute pain and a motivational pathway in adult rats: influence of early life pain experience. PLoS One. 2012; 7(3):e34316. PMC: 3314622. DOI: 10.1371/journal.pone.0034316. View

11.

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

12.

Abdulkader H, Freer Y, Garry E, Fleetwood-Walker S, McIntosh N . Prematurity and neonatal noxious events exert lasting effects on infant pain behaviour. Early Hum Dev. 2007; 84(6):351-5. DOI: 10.1016/j.earlhumdev.2007.09.018. View

13.

Anderson P, Doyle L . Neurobehavioral outcomes of school-age children born extremely low birth weight or very preterm in the 1990s. JAMA. 2003; 289(24):3264-72. DOI: 10.1001/jama.289.24.3264. View

14.

Hermann C, Hohmeister J, Demirakca S, Zohsel K, Flor H . Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain. 2006; 125(3):278-285. DOI: 10.1016/j.pain.2006.08.026. View

15.

Grunau R, Haley D, Whitfield M, Weinberg J, Yu W, Thiessen P . Altered basal cortisol levels at 3, 6, 8 and 18 months in infants born at extremely low gestational age. J Pediatr. 2007; 150(2):151-6. PMC: 1851896. DOI: 10.1016/j.jpeds.2006.10.053. View

16.

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

17.

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

18.

Loe I, Lee E, Luna B, Feldman H . Behavior problems of 9-16 year old preterm children: biological, sociodemographic, and intellectual contributions. Early Hum Dev. 2011; 87(4):247-52. PMC: 3180905. DOI: 10.1016/j.earlhumdev.2011.01.023. View

19.

Spangler R, Goddard N, Avena N, Hoebel B, Leibowitz S . Elevated D3 dopamine receptor mRNA in dopaminergic and dopaminoceptive regions of the rat brain in response to morphine. Brain Res Mol Brain Res. 2003; 111(1-2):74-83. DOI: 10.1016/s0169-328x(02)00671-x. View

20.

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