Official reprint from UpToDate®
www.uptodate.com ©2015 UpToDate®

Assessment of neonatal pain

Section Editor
Richard Martin, MD
Deputy Editor
Melanie S Kim, MD


Neonatal discomfort, stress, or pain may be associated with routine patient care (eg, physical examination and diaper changes), moderately invasive care measures (eg, suctioning, phlebotomy, and peripheral intravenous line placement), or more invasive procedures (eg, chest tube placement and circumcision).

Pain in the neonate can be classified into three categories [1]:

Acute or physiological pain occurs from skin-breaking procedures or tissue injury caused by diagnostic or therapeutic interventions. Infants admitted to the neonatal intensive care unit (NICU) repeatedly experience acute pain from an average of 12 to 16 invasive procedures each day [2,3].

Established pain occurs following surgery, localized inflammatory conditions (eg, abscess or thrombophlebitis), or birth-related trauma.

Prolonged or chronic pain results from severe diseases such as necrotizing enterocolitis or meningitis, or rare conditions such as scalded skin syndrome or Harlequin syndrome. (See "Vesiculobullous and pustular lesions in the newborn", section on 'Staphylococcal scalded skin syndrome'.)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Dec 2014. | This topic last updated: Nov 6, 2013.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2015 UpToDate, Inc.
  1. Anand KJ, Aranda JV, Berde CB, et al. Analgesia and anesthesia for neonates: study design and ethical issues. Clin Ther 2005; 27:814.
  2. Simons SH, van Dijk M, Anand KS, et al. Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates. Arch Pediatr Adolesc Med 2003; 157:1058.
  3. Carbajal R, Rousset A, Danan C, et al. Epidemiology and treatment of painful procedures in neonates in intensive care units. JAMA 2008; 300:60.
  4. American Academy of Pediatrics Committee on Fetus and Newborn, American Academy of Pediatrics Section on Surgery, Canadian Paediatric Society Fetus and Newborn Committee, et al. Prevention and management of pain in the neonate: an update. Pediatrics 2006; 118:2231.
  5. Franck LS, Allen A, Cox S, Winter I. Parents' views about infant pain in neonatal intensive care. Clin J Pain 2005; 21:133.
  6. Franck LS, Cox S, Allen A, Winter I. Parental concern and distress about infant pain. Arch Dis Child Fetal Neonatal Ed 2004; 89:F71.
  7. Anand KJ, Aranda JV, Berde CB, et al. Summary proceedings from the neonatal pain-control group. Pediatrics 2006; 117:S9.
  8. Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus. N Engl J Med 1987; 317:1321.
  9. Anand KJ, Brown MJ, Causon RC, et al. Can the human neonate mount an endocrine and metabolic response to surgery? J Pediatr Surg 1985; 20:41.
  10. Andrews K, Fitzgerald M. Cutaneous flexion reflex in human neonates: a quantitative study of threshold and stimulus-response characteristics after single and repeated stimuli. Dev Med Child Neurol 1999; 41:696.
  11. Lowery CL, Hardman MP, Manning N, et al. Neurodevelopmental changes of fetal pain. Semin Perinatol 2007; 31:275.
  12. Anand KJS. Fetal pain? Pain-Clinical Updates 2006; 14:1.
  13. Anand KJ, Maze M. Fetuses, fentanyl, and the stress response: signals from the beginnings of pain? Anesthesiology 2001; 95:823.
  14. Slater R, Cantarella A, Gallella S, et al. Cortical pain responses in human infants. J Neurosci 2006; 26:3662.
  15. Bartocci M, Bergqvist LL, Lagercrantz H, Anand KJ. Pain activates cortical areas in the preterm newborn brain. Pain 2006; 122:109.
  16. Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. Lancet 1987; 1:62.
  17. Craig KD, Whitfield MF, Grunau RV, et al. Pain in the preterm neonate: behavioural and physiological indices. Pain 1993; 52:287.
  18. Porter FL, Wolf CM, Miller JP. Procedural pain in newborn infants: the influence of intensity and development. Pediatrics 1999; 104:e13.
  19. Guinsburg R, Kopelman BI, Anand KJ, et al. Physiological, hormonal, and behavioral responses to a single fentanyl dose in intubated and ventilated preterm neonates. J Pediatr 1998; 132:954.
  20. Johnston CC, Strada ME. Acute pain response in infants: a multidimensional description. Pain 1986; 24:373.
  21. Stevens B, Johnston C, Petryshen P, Taddio A. Premature Infant Pain Profile: development and initial validation. Clin J Pain 1996; 12:13.
  22. Ballantyne M, Stevens B, McAllister M, et al. Validation of the premature infant pain profile in the clinical setting. Clin J Pain 1999; 15:297.
  23. Krechel SW, Bildner J. CRIES: a new neonatal postoperative pain measurement score. Initial testing of validity and reliability. Paediatr Anaesth 1995; 5:53.
  24. Holsti L, Grunau RE, Oberlander TF, et al. Body movements: an important additional factor in discriminating pain from stress in preterm infants. Clin J Pain 2005; 21:491.
  25. Sharek PJ, Powers R, Koehn A, Anand KJ. Evaluation and development of potentially better practices to improve pain management of neonates. Pediatrics 2006; 118 Suppl 2:S78.
  26. Fitzgerald M. The development of nociceptive circuits. Nat Rev Neurosci 2005; 6:507.
  27. Anand KJS, Bhutta AT, Hall RW. Long-term effects of repetitive pain in the neonatal period: neuronal vulnerability, imprinting, and plasticity. In: Perinatal programming: Early Life Determinants of Adult Health and Disease, Hodgson DM, Coe C (Eds), Taylor & Francis Medical Books, London 2006. p.197.
  28. Grunau RE, Oberlander TF, Whitfield MF, et al. Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 Weeks' postconceptional Age. Pediatrics 2001; 107:105.
  29. Taddio A, Shah V, Gilbert-MacLeod C, Katz J. Conditioning and hyperalgesia in newborns exposed to repeated heel lances. JAMA 2002; 288:857.
  30. Peters JW, Schouw R, Anand KJ, et al. Does neonatal surgery lead to increased pain sensitivity in later childhood? Pain 2005; 114:444.
  31. Grunau RE, Holsti L, Haley DW, et al. Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU. Pain 2005; 113:293.
  32. Taddio A, Katz J, Ilersich AL, Koren G. Effect of neonatal circumcision on pain response during subsequent routine vaccination. Lancet 1997; 349:599.
  33. Anand KJ, Runeson B, Jacobson B. Gastric suction at birth associated with long-term risk for functional intestinal disorders in later life. J Pediatr 2004; 144:449.
  34. Buskila D, Neumann L, Zmora E, et al. Pain sensitivity in prematurely born adolescents. Arch Pediatr Adolesc Med 2003; 157:1079.
  35. Anand KJ, Scalzo FM. Can adverse neonatal experiences alter brain development and subsequent behavior? Biol Neonate 2000; 77:69.
  36. Ruda MA, Ling QD, Hohmann AG, et al. Altered nociceptive neuronal circuits after neonatal peripheral inflammation. Science 2000; 289:628.
  37. Bhutta AT, Rovnaghi C, Simpson PM, et al. Interactions of inflammatory pain and morphine in infant rats: long-term behavioral effects. Physiol Behav 2001; 73:51.
  38. Anand KJ, Coskun V, Thrivikraman KV, et al. Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav 1999; 66:627.
  39. Anand KJ, Garg S, Rovnaghi CR, et al. Ketamine reduces the cell death following inflammatory pain in newborn rat brain. Pediatr Res 2007; 62:283.
  40. Porter FL, Grunau RE, Anand KJ. Long-term effects of pain in infants. J Dev Behav Pediatr 1999; 20:253.
  41. Maroney DI. Recognizing the potential effect of stress and trauma on premature infants in the NICU: how are outcomes affected? J Perinatol 2003; 23:679.
  42. Slater R, Fabrizi L, Worley A, et al. Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants. Neuroimage 2010; 52:583.
  43. Walker SM, Franck LS, Fitzgerald M, et al. Long-term impact of neonatal intensive care and surgery on somatosensory perception in children born extremely preterm. Pain 2009; 141:79.
  44. Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil 2006; 28:183.
  45. Maneyapanda SB, Venkatasubramanian A. Relationship between significant perinatal events and migraine severity. Pediatrics 2005; 116:e555.
  46. Mitchell A, Boss BJ. Adverse effects of pain on the nervous systems of newborns and young children: a review of the literature. J Neurosci Nurs 2002; 34:228.
  47. Hohmeister J, Kroll A, Wollgarten-Hadamek I, et al. Cerebral processing of pain in school-aged children with neonatal nociceptive input: an exploratory fMRI study. Pain 2010; 150:257.
  48. Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med 1992; 326:1.
  49. Taylor BJ, Robbins JM, Gold JI, et al. Assessing postoperative pain in neonates: a multicenter observational study. Pediatrics 2006; 118:e992.
  50. Hummel P, van Dijk M. Pain assessment: current status and challenges. Semin Fetal Neonatal Med 2006; 11:237.
  51. Duhn LJ, Medves JM. A systematic integrative review of infant pain assessment tools. Adv Neonatal Care 2004; 4:126.
  52. Grunau RE, Oberlander T, Holsti L, Whitfield MF. Bedside application of the Neonatal Facial Coding System in pain assessment of premature neonates. Pain 1998; 76:277.
  53. Blauer T, Gerstmann D. A simultaneous comparison of three neonatal pain scales during common NICU procedures. Clin J Pain 1998; 14:39.
  54. McNair C, Ballantyne M, Dionne K, et al. Postoperative pain assessment in the neonatal intensive care unit. Arch Dis Child Fetal Neonatal Ed 2004; 89:F537.
  55. Slater R, Cornelissen L, Fabrizi L, et al. Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial. Lancet 2010; 376:1225.
  56. Fabrizi L, Slater R, Worley A, et al. A shift in sensory processing that enables the developing human brain to discriminate touch from pain. Curr Biol 2011; 21:1552.
  57. Hummel P, Puchalski M, Creech SD, Weiss MG. Clinical reliability and validity of the N-PASS: neonatal pain, agitation and sedation scale with prolonged pain. J Perinatol 2008; 28:55.
  58. Lawrence J, Alcock D, McGrath P, et al. The development of a tool to assess neonatal pain. Neonatal Netw 1993; 12:59.
  59. Carbajal R, Paupe A, Hoenn E, et al. [APN: evaluation behavioral scale of acute pain in newborn infants]. Arch Pediatr 1997; 4:623.
  60. Carbajal R, Veerapen S, Couderc S, et al. Analgesic effect of breast feeding in term neonates: randomised controlled trial. BMJ 2003; 326:13.
  61. Johnston CC, Stevens BJ, Franck LS, et al. Factors explaining lack of response to heel stick in preterm newborns. J Obstet Gynecol Neonatal Nurs 1999; 28:587.
  62. Johnston CC, Stevens BJ, Yang F, Horton L. Differential response to pain by very premature neonates. Pain 1995; 61:471.
  63. Stevens B, McGrath P, Gibbins S, et al. Determining behavioural and physiological responses to pain in infants at risk for neurological impairment. Pain 2007; 127:94.
  64. Anand KJ. Pain assessment in preterm neonates. Pediatrics 2007; 119:605.
  65. van Dijk M, Koot HM, Saad HH, et al. Observational visual analog scale in pediatric pain assessment: useful tool or good riddance? Clin J Pain 2002; 18:310.
  66. Bergqvist L, Eriksson M, Kronsberg S, et al. Seeing through the blind! Ability of hospital staff to differentiate morphine from placebo, in neonates at a placebo controlled trial. Acta Paediatr 2007; 96:1004.
  67. Stevens BJ, Pillai Riddell R. Looking beyond acute pain in infancy. Pain 2006; 124:11.
  68. Pillai Riddell R, Racine N. Assessing pain in infancy: the caregiver context. Pain Res Manag 2009; 14:27.
  69. Dunbar AE 3rd, Sharek PJ, Mickas NA, et al. Implementation and case-study results of potentially better practices to improve pain management of neonates. Pediatrics 2006; 118 Suppl 2:S87.
  70. Anand KJ, International Evidence-Based Group for Neonatal Pain. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001; 155:173.
  71. Debillon T, Zupan V, Ravault N, et al. Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants. Arch Dis Child Fetal Neonatal Ed 2001; 85:F36.
  72. Hellerud BC, Storm H. Skin conductance and behaviour during sensory stimulation of preterm and term infants. Early Hum Dev 2002; 70:35.
  73. Harrison D, Boyce S, Loughnan P, et al. Skin conductance as a measure of pain and stress in hospitalised infants. Early Hum Dev 2006; 82:603.