Assessment of neonatal pain

Author
Kanwaljeet JS Anand, MBBS, DPhil, FAAP, FCCM, FRCPCH
Section Editor
Richard Martin, MD
Deputy Editor
Melanie S Kim, MD
Contributor disclosures
Kanwaljeet JS Anand, MBBS, DPhil, FAAP, FCCM, FRCPCH Nothing to
disclose.Richard Martin, MD Consultant/Advisory Boards: Discovery Labs [surfactant
therapy (lucinactant)]. Melanie S Kim, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When
found, these are addressed by vetting through a multi-level review process, and through
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All topics are updated as new evidence becomes available and our peer review process is
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Literature review current through: Apr 2016. | This topic last updated: Nov 06, 2013.
INTRODUCTION 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'.)

Care providers are expected to prevent any infant from experiencing pain if at all possible
[4-6]. Pain assessment is a necessary part of neonatal pain management, as an indication for
initiating therapy as well as assessing its effectiveness. It is challenging to detect and
measure the intensity of pain in neonates because of their inability to communicate with
care providers.
The need for effective pain management and the assessment of pain in neonates will be
reviewed here. Prevention and treatment of neonatal pain are discussed separately. (See
"Prevention and treatment of neonatal pain".)
DEFINITIONS This topic review uses the following terms as defined by the neonatal
pain-control group of the Newborn Drug Development Initiative [7]:
Pain An unpleasant somatic or visceral sensation associated with actual or potential
tissue damage.
Stress A disturbance of the dynamic equilibrium between an infant and his/her
environment that results in a physiologic response by the infant.
Stress or pain response The individual's physiologic response to pain or stress that is
characterized primarily by changes in four domains (ie, endocrine-metabolic, autonomic,
immunologic, and/or behavioral responses).
Analgesia Absence or reduction of pain in the presence of stimuli that would normally
be painful.
Pain control Reduction in the intensity and/or duration of pain.
BACKGROUND Historically, pain prevention and control have been underutilized in
neonates because of the following misconceptions:
Their pain pathways are unmyelinated or otherwise immature and cannot transmit painful
stimuli to the brain.
There is no alternative for verbal self-report, which remains the "gold standard" for
conveying a subjective experience like pain.
Pain perception is located only in the cortex, and thalamocortical connections must be
fully developed in order to allow pain perception.
The human infant does not have the psychological context in order to identify any
experiences as painful and this does not develop until two years or later.
Newborn infants are at greater risk for developing the adverse effects of analgesic or
sedative agents, or these drugs have adverse long-term effects on brain development and
behavior.

However, not one of these misconceptions is supported by the current evidence. Beginning
in the 1980s, accumulating evidence demonstrated that both preterm and term infants
experience pain and stress in response to noxious stimuli [8-10]. By the middle of the
second trimester, the human fetus has a highly differentiated and fully functional sensory
system [11-13]. Optical neuroimaging studies show increased cortical activation in the
somatosensory areas of the brain in preterm infants exposed to painful stimuli (eg, heelstick
or venipuncture) [14,15].
Numerous studies have documented neonatal responses to pain, which include autonomic
(eg, increases in heart rate, blood pressure), hormonal (eg, cortisol and catecholamine
responses), and behavioral changes (eg, facial grimace) [8,16-20]. These responses form
the basis of the many pain assessment tools used to evaluate acute pain in the neonate
[17,21-24]. (See 'Assessment of pain' below.)
Frequency of painful procedures Painful procedures are common in neonates, especially
in those in the neonatal intensive care unit (NICU). Analgesic therapy is often not given,
despite greater understanding that neonates experience pain [2,3,25].
The prevalence of untreated neonatal pain was best illustrated by a large prospective French
study of 430 neonates admitted to tertiary NICUs during a six-week time period beginning
in September 2005 [3]. All painful and stressful procedures were recorded for each
participant during the first 14 days following NICU admission. The following findings
were noted:
Overall, almost 70,000 first-attempt procedures were recorded, of which 70 percent were
painful and 30 percent were stressful. An additional 11,500 supplemental attempts were
performed, of which 90 percent were painful and 10 percent were stressful.
Neonates experienced a median of 115 procedures during the 14-day study period, of
which 75 were painful.
Of the 42,413 painful procedures, specific analgesic therapy for the therapy was provided
in 20.8 percent of patients, which included only nonpharmacologic therapy (18 percent),
only pharmacologic therapy (2 percent), and both nonpharmacologic and pharmacologic
therapy (0.4 percent). An additional 34 percent of patients were receiving concurrent
analgesia or anesthetic therapy for other reasons during the procedure.
Factors associated with greater use of specific preprocedural analgesia included
prematurity, the type of procedure, parental presence, surgery, daytime, and day of
procedure after the first day of admission. In contrast, mechanical and noninvasive
ventilation, and use of concurrent analgesia were associated with lower use of specific
preprocedural analgesia.
Effects of inadequately treated pain Accumulating data suggest that untreated or
inadequately treated neonatal pain may have long-term deleterious effects [26,27]. Several
studies have reported that repeated episodes of pain alter subsequent pain sensitivity and
reactivity [28-31]. For example, infants of diabetic mothers, who were exposed to repeated

heelsticks just after birth, exhibited more intense pain responses (facial grimacing and
crying) during later venipuncture compared with normal infants [29]. Infants exposed to
circumcision pain at birth experienced greater pain at immunization four to six months later
[32], whereas those exposed to gastric suctioning at birth evidenced threefold greater odds
of developing irritable bowel syndrome during adolescence or adulthood [33]. Adolescents
born prematurely also display higher somatic pain sensitivity than adolescents born at term
[34]. These findings and other animal studies substantiate the theory that repeated exposure
to neonatal pain leads to permanent changes in pain processing [35].
Neuroanatomical and behavioral changes have also been reported in adult animals that were
exposed to neonatal pain [36-38]. In one study, exposure to persistent hind paw pain in
newborn rats induced changes in primary afferent neurons and their spinal neuronal circuits
in adult animals, both at baseline and following sensory stimulation, compared with control
animals [36]. Another study showed that the neuroanatomical and behavioral changes
following repetitive inflammatory pain resulted from neuronal excitotoxicity, which was
ameliorated by ketamine analgesia [39]. It remains unclear whether such long-term effects
will occur in adult humans exposed to prolonged pain as neonates [26,40,41]. It is
increasingly recognized, however, that exposure to repetitive pain in early life may expose
patients to greater risks of developing increased pain sensitivity and/or chronic pain
syndromes during their subsequent lifespan [42-47].
Interventions that reduce neonatal stress also improve clinical outcomes. In infants that
underwent surgery, those who received greater amounts of anesthesia and analgesia
compared with controls had reduced levels of norepinephrine, epinephrine, glucagon,
aldosterone, and cortisol, decreased postoperative morbidity (eg, sepsis, metabolic acidosis,
disseminated intravascular coagulation), and a lower mortality rate [16,48]. Subsequent
trials have confirmed the findings of improved clinical outcomes following anesthetic
reduction of surgical stress.
SYSTEMATIC APPROACH The increased appreciation that neonates experience pain,
the frequency of painful procedures they endure, and the effects of unrelieved pain have led
to efforts to improve pain control in neonates.
In 2006, the American Academy of Pediatrics and the Canadian Paediatric Society
published new guidelines recommending that each healthcare facility that treats neonates
establish a neonatal pain control program [4]. (See "Prevention and treatment of neonatal
pain".)
These recommendations included:
Routine assessment for the detection of pain
Reduction of the number of painful procedures
Guidelines and protocols to prevent/reduce pain from invasive bedside procedures (eg,
chest tube placement) or following surgery

A multicenter, observational study found that postoperative pain assessments by clinicians

increased the odds of receiving analgesia fourfold as opposed to those not assessed [49],
thus highlighting the importance of pain assessment as a component of routine clinical
evaluation.
ASSESSMENT OF PAIN Accurate pain assessments in the neonate remain challenging
because of the inability of the infant to self-report. Since pain assessment is an essential
prerequisite for optimal pain management, several scoring tools have been developed for
this purpose.
Pain assessment tools Available methods for neonatal pain assessment are either
unidimensional (eg, physiological or behavioral parameter) or multidimensional (include
physiologic, behavioral, and contextual parameters) [1,4,50,51]. Several multidimensional
assessment tools with demonstrated validity, reliability, and clinical utility are currently
used in the neonatal intensive care unit (NICU) [17,21-24,49-54]. These tools are based
upon the following physiologic and behavioral indicators readily assessed at the bedside.
Physiologic parameters - Changes in heart rate, respiratory rate, blood pressure, vagal
tone, heart rate variability, breathing pattern, oxygen saturation, intracranial pressure,
palmar sweating, skin color, or pupillary size. Some studies have used alteration in
physiological electroencephalographic (EEG) or electromyographic (EMG) patterns to
assess pain, but these methods are not considered as valid or reliable, or representative of
pain perception [55,56].
Behavioral responses Crying patterns, acoustic features of infant crying, facial
expressions, hand and body movements, muscle tone, sleep patterns, behavioral state
changes, and consolability. In infants, total facial activity and cluster of specific facial
findings (brow bulge, eye squeeze, nasolabial furrow, and open mouth) are associated with
acute and postoperative pain [17,21-24,52,54].
The tools most commonly used in the NICU for acute pain assessment include the
following (table 1):
PIPP Premature Infant Pain Profile [21]
N-PASS Neonatal Pain Agitation and Sedation Scale [57]
NIPS Neonatal Infant Pain Scale [58]
CRIES Crying, Requires Oxygen Saturation, Increased Vital Signs, Expression,
Sleeplessness [23]
NFCS Neonatal Facial Coding System [52]
DAN DouleurAigu Nouveau-n scale [59,60]

Premature infants, the most likely group to undergo painful procedures, are less likely to
consistently demonstrate the responses to pain selected by these assessment tools
[18,52,61-63]. These scales have been evaluated for acute pain and some for postoperative
pain, but none of these methods assess persistent pain [64].
Two multicenter studies illustrate that there is a wide range of pain assessment tools used in
NICUs.

In the first study, 12 sites evaluated by the 2002 Neonatal Intensive Care Quality
Improvement Collaborative used five different assessment tools [25].
In the second study from the Child Health Accountability Initiative, 10 sites used eight
different assessment tools [49].
Limitations The inability to select a single assessment tool is based in part upon the
following limitations [64]:
Most tools were developed and validated for neonates undergoing acute pain (eg,
venipuncture, heelstick).
Many of the signs used in these assessment tools require the subjective evaluation by
observers. As a result, there is significant interobserver variability in the evaluation of
behavioral responses that can be reduced with multidisciplinary training of the staff [65,66].
Some parameters may require specialized equipment at the bedside (eg, heart rate
variability, palmar skin conductance).
Some measures are not available in real-time to be clinically useful (eg, serum or salivary
cortisol levels).
Responses to pain may be decreased in neurologically impaired neonates [58,63] and
absent in those who receive paralytic medications.
Tools for the assessment of persistent or prolonged pain in neonates (due to major surgery,
osteomyelitis, or necrotizing enterocolitis) have not been developed or completely validated
[57,67]. During episodes of persistent pain, neonates may enter a passive state, with limited
or no body movements, an expressionless face, reduced variability in heart rate and
respiratory rate, and decreased oxygen consumption [4,64]. Thus, assessment tools based
on these indicators will not adequately detect and assess the intensity of prolonged neonatal
pain [61,64].
Based upon these observations, universal application of one of these assessment tools is not
advisable. The choice of the assessment pain tool is dependent upon the neonatal
population to be assessed and the different types of pain that need to be evaluated.
In addition, behavioral responses are dependent on the subjective judgement of care
providers [64]. Significant interobserver variability can be reduced, but not entirely
eliminated, by training or greater experience. Clinicians performing pain assessments must
also recognize potentially important relationships between the infants pain expression and
the behavior, including sensitivity and receptivity, of the infants care providers [68].
Efforts to improve the objectivity and accuracy of assessment tools with the use of
neuroimaging and neurophysiologic techniques to measure brain activity during acute or
prolonged pain have been largely unsuccessful [14,15,64]. Their goal is to provide the

clinician a reliable and accurate method to detect pain and to quantify its intensity at the
bedside, but that goal has not been achieved.
Because of our limited ability to detect and quantify pain in neonates, especially preterm
infants, we suggest that pain control measures be administered preemptively to prevent or
reduce pain due to known noxious stimuli [25,69]. As a general rule, anything that causes
pain in adults or older children will also cause pain in neonates, regardless of their
gestational age. (See "Prevention and treatment of neonatal pain".)
Staff training Staff recognition of neonatal pain will determine whether or not neonates
receive adequate pain control [49,70]. In a multicenter observational study, the
documentation of clinician pain assessment was the only significant factor associated with
the use of pharmacologic analgesia after surgery [49]. In contrast, the type of surgery
(major or minor) was not associated with the administration of pharmacologic therapy.
Thus, each facility that cares for infants should adopt an assessment strategy for the
detection and documentation of pain.
Institution of a pain management program increases the awareness of the staff that pain
occurs routinely in the NICU [49,66,70] and that its control is an important clinical goal [57]. The effective use of a clinical assessment tool requires mandatory training of the staff to
improve interobserver reliability and to educate the staff on the limitations of the selected
tool [64].
Our approach At our institution, we assess pain at least every four hours when vital
signs are measured, and after each painful or therapeutic intervention. We use the PIPP
(Premature Infant Pain Profile) for assessment of acute or postoperative pain [21,54] and
the N-PASS (Neonatal Pain Agitation and Sedation Scale) for the assessment of prolonged
pain [57]. We also utilize various contextual factors, and other behavioral or physiological
indicators suggesting inadequate analgesia (eg, pupillary dilation). If parents are available,
we ask for their opinion: do they feel that their baby is in pain? For prolonged pain in
neonates, we should also consider the utility of EDIN (EchelleDouleurInconfort NouveauNe) as a clinical tool [71] and the use of a device that measures neonatal stress [72,73].
SUMMARY AND RECOMMENDATIONS
Neonates experience pain from the same interventions or clinical conditions as older
children and adults. Infants who are cared for in the neonatal intensive care unit (NICU)
may experience pain routinely, randomly, frequently, and for prolonged periods of time.
(See 'Frequency of painful procedures' above.)
Untreated or inadequately treated neonatal pain may have immediate and long-term
effects including altered pain sensitivity and reactivity, and other adverse health outcomes.
(See 'Effects of inadequately treated pain' above.)
Each healthcare facility that treats neonates should establish a neonatal pain control
program that incorporates:

Standardized methods for the routine assessment of pain by clinicians and nurses.
Reduction of the number of painful procedures and physical handling. (See "Prevention
and treatment of neonatal pain", section on 'Reduction of painful events'.)
Guidelines and protocols to treat acute and prolonged pain due to neonatal diseases,
invasive procedures, or other aspects of NICU care. (See "Prevention and treatment of
neonatal pain".)
Assessment of neonatal pain is challenging because of the inability of the infant to
communicate with care providers. Assessment tools based on contextual factors,
physiologic, and behavioral indicators have been developed to detect and measure the
intensity of neonatal pain (table 1). The most commonly used tools include multiple
indicators and have demonstrated validity, reliability, and clinical utility. (See 'Pain
assessment tools' above.)
A single assessment tool has not been adopted universally because each tool was
developed and validated for selected populations and clinical settings. Most assessment
tools may not detect prolonged pain, pain in extremely low birth weight premature infants
(birth weight below 1000 g), or in those receiving paralytic medications. (See 'Pain
assessment tools' above.)
Despite the limitations of currently available tools, we recommend that each facility that
cares for infants should adopt an assessment strategy for the detection of pain. A systematic
approach increases the awareness of the clinical staff that pain is a pervasive finding in the
NICU. Increased staff awareness may improve neonatal pain control. (See 'Pain assessment
tools' above.)
In our practice, we use PIPP (Premature Infant Pain Profile) for assessment of acute or
postoperative pain and the N-PASS (Neonatal Pain Agitation and Sedation Scale) for the
assessment of prolonged pain. (See 'Our approach' above.)
Because of the limited ability to detect and quantify neonatal pain, we recommend that
pain control measures should be administered to prevent or reduce pain due to known
noxious stimuli (Grade 1B). (See "Prevention and treatment of neonatal pain".)

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