Pain in the Premature Infant

The Centers for Disease Control and Prevention reports that in 2014 about one of every ten infants was born premature in the United States. Prematurity is the leading contributor to infant death, especially for those infants born prior to 32 weeks, as well as the leading contributor to long-term neurological disabilities in children.1 After birth, preterm neonates are admitted into a Neonatal Intensive Care Unit (NICU) where they experience a number of painful procedures at a time when nociceptive pain pathways are immaturely operable.2-5 The pathways that signal pain in the preterm neonate do not reflect the same pathways that are part of the mature nervous system in healthy adult humans.3,4,6

Additionally, during this period, vast anatomical and physiological changes are occurring including the rapid growth of the neonatal brain’s microstructure along with biological stress systems.2-4 An important consideration of this rapid period of growth is that neuronal structures are highly receptive to external stimuli, and at this developmental level, these structures are not anticipating external stimuli such as pain exposure.2-4 Instead, this evolving circuitry relies on non-noxious sensory stimuli as would be expected in the healthy neonate; thus, there is increased difficulty in determining whether the stimuli is noxious or not noxious.2-4,7,8 This early introduction of noxious stimuli causes injury and in turn changes the mechanisms involved in pain processing.2-5,7 Results of these painful exposures have been linked to adverse outcomes with long-standing effects; some of which continue through childhood and into adulthood.3,5,6,9-14

Pain Management
There are two essential components needed in pain management; they are pain assessment and measurement.15 Pain assessment is a comprehensive and multidimensional approach and requires recognition of the behavioural, physiological, and/or metabolic changes exhibited by the neonate in response to pain. Pain measurement results in a number or quantitative value yielding a composite score that influences the selection of an intervention.15

Neonatal pain, its assessment and management is a challenging phenomenon based on the complex interplay of a multitude of variables.16 Each variable – Gestational Age (GA), severity of illness, sedation levels and pathology – i.e., neurological impairment – has the potential to influence the neonates’ display of pain and as a result can impact the nurses’ interpretation and management of it.17-21 For example, GA affects the type and frequency of extremity movement, and preterm neonates may not exhibit movement due to decreased energy reserves.18 Furthermore, preterm neonates who experience frequent painful procedures may demonstrates a flaccid or limp tone with chaotic movement.18,20 Thus, nurses can misinterpret these behavioral responses as an indication of no pain. Furthermore, lack of agreement among clinicians on treatment and the neonates’ inability to self-report their pain experience inhibits the creation of well-defined pain assessment and management strategies.22

Interdisciplinary Collaboration
Prevention and improved management of pain requires strong interdisciplinary collaboration in the selection and application of appropriate interventions.21,23 This interdisciplinary plan must include careful planning and execution of analgesic interventions that target high frequency painful procedures in order to prevent the damaging effects of pain exposure.11 Consistent assessment and management of preterm neonatal pain as reflected in clinical documentation requires not simply the development of but adherence to standardized written guidelines based on current evidence as well as staying current on topics related to pain and its management through continuing education.23

1. Preterm birth. Centers for Disease Control and Prevention.
Accessed February 26, 2016.

2. Fitzgerald M. The development of nociceptive circuits. Nat Rev Neurosci. 2005; 6(7): 507-520. doi: 10.1038/nrn1701.

3. Ranger M, Grunau, RE. Early repetitive pain in preterm infants in relation to the developing brain. Pain Manag. 2014; 4(1): 57-67. doi: 10.2217/pmt.13.61.

4. Vinall J, Grunau, RE. Impact of repeated procedural pain-related stress in infants born very preterm. Pediatr Res. 2014; 75(5): 584-587. doi: 10.1038/pr.2014.16.

5. Walker S. Biological and neurodevelopmental implications of neonatal pain. Clin Perinatol. 2013; 40(3): 471-491. doi: 10.1016/j.clp.2013.05.002.

6. Vinall J, Miller SP, Chau V, Brummelte S, Synnes AR, Grunau, RE. Neonatal pain in relation to postnatal growth in infants born very preterm. Pain. 2012; 153(7): 1374-1381. doi: 10.1016/j.pain.2012.02.007.

7. Beggs S, Torsney C, Drew LJ, Fitzgerald M. The postnatal reorganization of primary afferent input and dorsal horn cell receptive fields in the rat spinal cord is an activity-dependent process. Eur J Neurosci. 2002; 16(7), 1249-1258.

8. Granmo M, Petersson, P, Schouenborg, J. Action-based body maps in the spinal cord emerge from a transitory floating organization. J Neurosci. 2008; 28(21), 5494-5503. doi: 10.1523/JNEUROSCI.0651.08.2008.

9. Anand KJS, Rovnaghi C, Walden M, Churchill, J. Consciousness, behavior, and clinical impact of the definition of pain. Pain Forum. 1999; 8(2): 64-73. doi: 10.1016/S1082-3174(99)70029-2 .

10. Brummelte S, Grunau RE, Chau V, et al. Procedural pain and brain development in premature newborns. Ann Neurol. 2012; 71(3): 385-389. doi: 10.1002/ana.22267.

11. Cruz MD, Fernandes AM, Oliveira CR Epidemiology of painful procedures performed in neonates: A systematic review of observational studies. Eur J Pain. 2016; 20(4), 489-498. doi: 10.1002/ejp.757. Epub 2015 Jul 29.

12. Doesburg SM, Chau CM, Cheung TP, et al. Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age. Pain. 2013; 154(10), 1946-1952. doi: 10.1016/j.pain.2013.04.009.

13. Grunau RE, Hostil L, Peters JWB. Long term consequences of pain in human neonates. Semin Fetal Neonatal Med. 2006; 11(4), 268-275. doi: 10.1016/j.siny.2006.02.007

14. Walker SM, Franck LS, Fitzgerald M, Myles J, Stocks J, Marlow N. Long-term impact of neonatal intensive care and surgery on somatosensory perception in children born extremely preterm. Pain. 2009; 141(1-2), 79-87. doi: 10.1016/j.pain.2008.10.012.

15. Cong X, McGrath JM, Cusson RM, Zhang D. Pain assessment and measurement in neonates: An updated review. Adv Neonatal Care, 2013; 13(6), 379-395. doi: 10.1097/ANC.0b013e3182a41452.

16. Hatfield LA, Ely EA. Measurement of acute pain in infants: A review of behavioral and physiological variables. Biol Res Nurs. 2015; 17(1), 100-111. doi: 10.1177/1099800414531448.

17. Grunau RE, Tu, MT. Long-term consequences of pain in human neonates. In: Anand KJS, Stevens BJ, McGrath PJ. eds. Pain Research and Clinical Management: Pain in Neonates and Infants. 3rd ed. Philadelphia, PA: Elsevier; 2007: 45-55.

18. Raeside L. Neonatal pain: Theory and concepts. Working papers in Health Sciences. 2013; 1(4), 1-6. ISSN: 2051-6266/20130020

19. Ranger M, Johnston CC, Anand KJS. Current controversies regarding pain assessment in neonates. Semin Perinatol. 2007; 31(5), 283-288. doi: 10.1053/j.semperi.2007.07.003.

20. Stevens BJ, Riddell RRP, Oberlander TE, Gibbins S. (2007). Assessment of pain in neonates and infant. In Anand KJS, Stevens BJ, McGrath PJ. eds. Pain Research and Clinical Management: Pain in Neonates and Infants. 3rd ed. Philadelphia, PA: Elsevier: 67-90.

21. van Dijk M, Tibboel D. Update on pain assessment in sick neonates and infants. Pediatr Clin North Am. 2012; 59(5), 1167-1181. doi: 10.1016/j.pcl.2012.07.012

22. Raeside L. Physiological measure of assessing infant pain: A literature review. Br J Nurs. 2011; 20(21), 1370 – 1376. doi: 10.12968/bjon.2011.20.21.1370.

23. American Academy of Pediatrics, Committee on Fetus and Newborn and section on Anesthesiology and Pain Medicine. Prevention and management of procedural pain in the neonate: An update. Pediatrics. 2016; 137(2), e20154271, doi: 10.1542/peds.2015-4271.

Nancy Murphy is an assistant professor of nursing at Temple University in Philadelphia.

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