Pain evaluation after a non-nociceptive stimulus in preterm infants during the first 28 days of life ☆ Adriana Cardoso Rodrigues, Ruth Guinsburg ⁎ Division of Neonatal Medicine, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, Brazil abstract article info Article history: Received 23 April 2012 Received in revised form 9 July 2012 Accepted 7 August 2012 Keywords: Infant, preterm Pain Pain perception Pain measurement Background: Protective mechanisms that modulate and lead to habituation to pain are immature in preterm newborn infants. Aims: To evaluate if a routine non-painful handling will be perceived as painful throughout the neonatal pe- riod in newborn infants with 28–32 weeks of gestational age. Study design: Prospective cohort study. Subjects: 36 preterm infants without malformations evaluated for pain during a diaper change. Outcome measures: Patients were studied at three times (5 min prior, during, and 3 min after the diaper change) during five moments (72 h, 7, 14, 21 and 28 days of life) by evaluation of heart rate, oxygen satura- tion and 3 validated pain assessment tools: the Neonatal Infant Pain Scale (NIPS), the Behavioral Indicators of Infant Pain (BIIP) and Premature Infant Pain Profile (PIPP). Results were analyzed by repeated measures ANOVA adjusted for gender, gestational age at birth, number of painful procedures and use of opioids. Results: Patients had, at birth, mean gestational age of 30.2 ± 1.4 weeks, birthweight of 1257 ± 238 g, with 50% males. Analysis of pain assessment tools did not show increase of pain presence or pain scores at the five sequential evaluation moments. The variation of oxygen saturation during the three study times was similar at the different post-natal ages, but heart rate variation increased significantly from 72 h until the 28th day of life. Conclusions: In preterm infants, the non-nociceptive handling does not trigger pain responses even after 28 days of neonatal care, which includes the experience of repetitive procedural pain. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Painful events are frequent in newborns that require intensive care. Simons et al. [1] observed 151 newborns during their first 14 days of hospitalization in an intensive care unit (ICU) and found that each one was subjected to an average of 14 painful procedures per day. Between 2005 and 2006, Carbajal et al. [2] analyzed 430 newborns admitted to tertiary healthcare units in the Paris area dur- ing their first 14 days of life, and each one was subjected to an aver- age of 10 painful procedures per day. Nociception is an activity induced in the nervous system by stim- uli arising from tissue damage and that involves peripheral sensory receptors, i.e., nociceptors, whose fibers make synapses at the dorsal horn of the spinal cord. During the development of the nervous sys- tem in prenatal and postnatal life, the projections of the C-fibers are the last group of primary afferents to penetrate the dorsal gray mat- ter. The A-fibers are also involved in the transmission of pain; they appear earlier in prenatal life and might be mechanoreceptors (Aβ) or mechanoreceptors and nociceptors (Aδ). In adults, the endings of Aβ fibers are restricted to laminae II and IV of the posterior spinal horn, but in fetuses and newborns, they extend dorsally towards lam- inae I and II until they reach the surface of the gray matter at the dor- sal horn of the spinal cord, thus increasing the field of medullary reception of nociceptive stimuli [3]. The amplification of neonatal responses to mechanical and/or nociceptive stimuli, even when they are weak, is further potentiated by the immaturity of the cor- tical descending modulating pathways, which become functional later in postnatal life in animal models and most likely also in humans [3–5]. Thus, newborns, and particularly the preterm infants, exhibit re- sponses to painful stimuli; however, rather than being specific, such responses are typically exaggerated and generalized [5]. Preterm in- fants subjected to multiple painful stimuli during their adaptation to postnatal life might be vulnerable to the consequences of the repeti- tion of noxious stimuli because the protective mechanisms that mod- ulate and lead to habituation to pain are immature. It is not yet clear whether, during hospital stay, preterm infants exhibit and possibly feel increasing pain as a consequence of the nociceptive stimuli to which they are subjected and the stressful environment where the as- sistance required for their survival is provided. Early Human Development 89 (2013) 75–79 ☆ Funding: ACR received a scholarship from CAPES-CNPq of the Ministry of Science and Technology, Brazil. ⁎ Corresponding author at: Rua Vicente Felix 77 apt 09, São Paulo, SP, 01410‐020, Brazil. Tel./fax: +55 11 5084 0535, +55 11 5579 1676. E-mail address: ruthgbr@netpoint.com.br (R. Guinsburg). 0378-3782/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.earlhumdev.2012.08.002 Contents lists available at SciVerse ScienceDirect Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev