Journal of Neonatal Surgery 2013;2(2):19

REVIEW ARTICLE

Pain Relief in Neonates

Lalitha Krishnan*

Department of Pediatrics, Pondicherry Institute of Medical sciences

It seems unbelievable how long it took the medi- thought capable of interpreting pain in a man-
cal community to realize that newborns also feel ner similar to that of adults. On a theoretical
pain. basis, it was also argued that a high threshold
of painful stimuli may be adaptive in protecting
It is the basic right of every individual, irre- infants from pain during birth. These tradi-
spective of age or size, to have alleviation of tional views have led to a widespread belief in
pain. Pain in newborn infants is a ubiquitous the medical community that the human neo-
phenomenon. All newborns, even normal ones, nate or fetus may not be capable of perceiving
will experience iatrogenic pain in the first days pain [1].
of life, commencing with vitamin K injection
and blood collection for sugars, bilirubin or Definitions
metabolic screening before discharge from the
hospital. Neonates admitted to present day ne- Pain: The International Association of the Study
onatal intensive care units (NICU) are con- of Pain (IASP) [2] defines that pain is “an un-
stantly exposed to pain, discomfort or noxious pleasant sensory and emotional experience as-
stimuli of variable intensity for a variety of rea- sociated with actual or potential tissue damage
sons. These include major surgical procedures, or described in terms of such damage”. Ac-
needle pricks for blood drawing and cording to the IASP, pain is always subjective.
cannulations. The painful situation may be Each individual learns the application of the
short lived or chronic as in the case of ne- word through experiences related to injury in
crotizing enterocolitis and prolonged ventila- early life”
tion. Even apparently innocuous care giving
procedures like diaper changes, daily weighing However, this definition of pain by the IASP
and removal of adhesive tape results in noxious does not apply to humans incapable of self-re-
stimuli. All these events, especially in preterm porting pain e.g. newborn and older infants.
infants individually or cumulatively, result in Anand and coworkers [3] state that the “rela-
adverse sequelae in the form of death, poor tionships between feeling pain and reporting
neurologic outcomes, abnormal somatization pain are highly context-dependent “.
and response to pain later in life.
Since the 1980’s it has become increasingly
Neonatal pain myths evident that the fetus and newborn perceives
and responds to pain. If pain is prolonged or
Evaluation of pain is considered difficult in ne- repetitive, the developing pain system may be
onates and young infants as pain has been modified permanently, resulting in altered pro-
considered a subjective phenomenon. Early cessing at the spinal and supraspinal levels [4].
studies of neurologic development concluded Over the last several years, evidence from both
that neonatal responses to painful stimuli were clinical and preclinical research has shown that
decorticate in nature and that perception or newborns are more sensitive to pain than older
localization of pain was not present. Further- infants, children, and adult.
more, because neonates may not have memo-
ries of painful experiences, they were not For healthy newborns painful experiences are
limited to a heel prick or venepuncture for met-

* Corresponding Author EL-MED-Pub Publishers.

http://www.elmedpub.com
 Pain Relief in Neonates

abolic screening or intramuscular injection of as an index of immaturity and often cited as

vitamin K or vaccines. For preterm or ill term- reason for neonates to be incapable of feeling
neonates, the experience is very different. They pain. But even in the peripheral nerves of
are exposed to repeated procedural pain [5], adults, nociceptive impulses are carried
extensive tissue damage resulting from surgery, through unmyelinated (C-polymodal) and thinly
or the invasiveness of endotracheal tubes myelinated (A-delta) fibers [10]. Moreover, pain
placed for mechanical ventilation. Thus, at a pathways to the spinal cord, brain stem and
time when most healthy term infants are thalamus are completely myelinated by 30
learning about their environment and preterm weeks; whereas the thalamo-cortical pain fibers
infants are growing in the protective uterine in the posterior limb of the internal capsule and
environment, approximately 8% of neonates are corona radiata are myelinated by 37 weeks [11].
coping with pain that, if left untreated, will in- Infants as young as 25 weeks post menstrual
terfere with normal growth and development age (PMA) have been shown to have cortical re-
[6]. Multiple sources of clinical and experi- sponses to noxious stimuli [12, 13]. Near infra-
mental evidence support the need for providing red spectroscopy studies in preterm infants
adequate analgesia/anesthesia for newborns from 28-36 weeks gestation undergoing tactile,
who undergo invasive procedures (medical, non-noxious and painful stimuli (venepuncture)
surgical, diagnostic, and therapeutic) or de- found that somatosensory cortical activation
velop conditions associated with a significant occurs bilaterally following unilateral stimula-
component of pain (eg, skin burns, necrotizing tion. These suggest that neonates do have the
enterocolitis) [7]. required neuronal connections to experience
the affective components of pain.
Nociception: This is defined as the ability to feel
pain caused by the stimulation of a nociceptor. Pain neurotransmitters
Nociceptors are pain receptors in the somatic
and visceral organs that can detect mechanical, Various substances have been identified for
thermal or chemical changes above a set transmission and control of pain but substance
threshold. Once stimulated, a nociceptor P is the one best investigated in babies in
transmits a signal along the spinal cord to the whom significant levels were demonstrated [14].
brain. Nociception triggers a variety of auto- Endogenous opioids are released in the human
nomic responses and may also result in a sub- fetus at birth and in response to fetal and neo-
jective experience of pain in conscious beings. natal distress [15].
It comprises of four stages; transduction,
transmission, modulation and perception. Changes during pain

In literature, terms relating to pain and noci- Physiological:

ception are used interchangeably and in this
review the two will be considered the same. Changes in heart rate, oxygenation and palmar
sweating have been observed in neonates un-
Development of nociception in the fetus and dergoing painful clinical procedures. The mag-
newborn: The neural pathways for nociception nitude of changes in the heart rate was related
as shown above are traceable in the newborn to the intensity and duration of the stimulus
and the density of pain fibres in the skin are and to the individual temperaments of the ba-
similar to that of adults [8]. Electron micros- bies. Large fluctuations in oxygenation above
copy and immunocytochemical studies show and below an arbitrary "safe" range of 50 to 100
that the development of various types of cells in mm Hg have been observed during various sur-
the dorsal horn (along with their laminar ar- gical procedures in neonates. Tracheal intuba-
rangement, synaptic interconnections, and spe- tion in awake preterm and full-term neonates
cific neurotransmitter vesicles) begins before 13 caused significant hypoxemia together with in-
to 14 weeks of gestation and is completed by 30 creases in arterial blood pressure and intracra-
weeks [9]. Lack of myelination has been used nial pressure. The increases in intracranial

Journal of Neonatal Surgery Vol. 2(2); 2013

 Pain Relief in Neonates

pressure with intubation were abolished in allow transmission of painful stimuli in the
preterm neonates who were anesthetized [16]. neonate.
In addition, infants' cardiovascular responses 2. Pain in newborns is often unrecognized and
to tracheal suctioning were abolished by opiate- undertreated. Neonates do feel pain, and
induced analgesia [17]. analgesia should be prescribed when indicated
during medical care.
Hormonal and Metabolic: 3. If a procedure is painful in adults it should
be considered painful in newborns, even if they
Plasma renin activity increased after vene- are preterm.
puncture in full-term neonates. In preterm ne- 4. Compared with older age groups, newborns
onates receiving ventilation therapy, chest may experience a greater sensitivity to pain and
physiotherapy and endotracheal suctioning are more susceptible to the long-term effects of
showed large increases in plasma epinephrine painful stimulation.
and norepinephrine; this response was de- 5. Adequate treatment of pain may be asso-
creased in sedated infants [18]. In neonates ciated with decreased clinical complications
undergoing circumcision without anesthesia, and decreased mortality.
plasma cortisol levels increased markedly dur- 6. Sedation does not provide pain relief and
ing and after the procedure. Preterm and full- may mask the neonate's response to pain.
term neonates who underwent surgery under 7. A lack of behavioural responses (including
minimal anesthesia documented a marked re- crying and movement) does not necessarily
lease of catecholamines, growth hormone, glu- indicate a lack of pain.
cagon, cortisol, aldosterone, and other cortico- 8. Severity of pain and the effects of analgesia
steroids, as well as suppression of insulin se- can be assessed in the neonate. Health care
cretion. These results indicate that the noci- professionals have the responsibility for
ceptive stimuli during surgery performed with providing a systematic approach to pain
minimal anesthesia were responsible for the management including assessment, prevention
massive stress responses of neonates. and treatment of pain in neonates.
9. Treatment should include the appropriate
Consequences of pain use of environmental, behavioural and
pharmacological interventions.
Medical:
10. Environment should be as conducive as
possible to the well being of the neonate and
Pain may worsen already compromised physio-
family.
logical states like hypoxia, hypercarbia, acido-
11. Education and validation of competency in
sis, hyperglycemia or respiratory distress. Ba-
pain assessment and management for all ne-
bies who received good peri-operative analgesia
onatal doctors and nurses, is a professional re-
showed stable course and faster recovery.
sponsibility of clinical units.
Neurodevelopmental:
Neonatal pain control: All neonatal units are
Preterm infants <1000g who have been exposed required to have a neonatal pain control pro-
to repeated noxious stimuli are less responsive gram which emphasizes the following [19].
to painful stimuli at 18 months of age but at 10
1. Providing routine assessments to detect
years of age rate medical pain higher than their
neonatal pain
normal weight counterparts
2. Reducing the number of painful procedures
General principles in the prevention and man- 3. Preventing or treating acute pain from
agement of pain in newborns: bedside invasive procedures
4. Anticipating and treating postoperative pain
1. Neuroanatomical components and neuro- following surgery
endocrine systems are sufficiently developed to 5. Avoiding prolonged or repetitive pain and
stress during neonatal intensive care

Journal of Neonatal Surgery Vol. 2(2); 2013

 Pain Relief in Neonates

Pain assessment scales: The fifth vital sign ment. Documentation of pain is also crucial as
[20] there can be variation in pain perception in ba-
bies between various caregivers. Many pain
Selecting the most appropriate tool for evalu- scoring tools exist and a few that are used
ating neonatal pain is essential to its manage- commonly are given in Table 1.

Table 1: Commonly Used Measures of Pain in Neonates

Measure Variables Included Type of Pain Psychometric Testing

PIPP (Premature Infant Heart rate, oxygen Procedural, postoperative Reliability, validity,
Pain Profile22 saturation, facial (minor) clinical utility well
actions; takes state and established
gestational age into
account
NIPS (Neonatal Infant Facial expression, Procedural Reliability, validity
Pain Score)23 crying, breathing
patterns, arm and leg
movements, arousal
NFCS (Neonatal Facial Facial actions Procedural Reliability, validity,
Coding System)23 clinical utility, high
degree of sensitivity to
analgesia
N-PASS (Neonatal Pain, Crying, irritability, Postoperative, procedural, Reliability, validity,
Agitation, and Sedation behavioral state, facial ventilated includes sedation end
Scale)24 expression, extremity of scale, does not
tone, vital signs distinguish pain from
agitation
CRIES (Cry, Requires Crying, facial expression, Postoperative Reliability, validity
oxygen, Increased vital sleeplessness, requires
signs, Expression, oxygen to stay at >95%
Sleeplessness)25 saturation, increased
vital signs
COMFORT Scale26 Movement, calmness, Postoperative, critical Reliability, validity,
facial tension, alertness, care, developed for clinical utility
respiration rate, muscle sedation, recently
tone, heart rate, blood validated for postoperative
pressure pain in 0- to 3-year-old
infants

Pain management in neonates effects [28]. Non-pharmacological pain relief

strategies are convenient, inexpensive, can be
Multiple classes of drugs have been evaluated used without prescriptions, and are also well
for the prevention and management of neonatal tolerated by infants. Procedural pain in
pain and stress, including opioid analgesics, newborns has been relieved by non-
local anesthetics, general anesthetics, seda- pharmacological interventions, such as
tives, hypnotics, non-steroidal anti-inflamma- nonnutritive sucking (NNS) [29] swaddling,
tory drugs (NSAIDs), and sucrose (Table 2). facilitated tucking [30], oral sucrose [31, 32],
Although much research has been performed breast feeding [33] and skin-to-skin contact
with these agents, many questions remain [34].
unanswered thus preventing the optimal use of
these drugs in clinical practice [27]. Pain in Behavioral approach:
neonates can be managed by pharmacological
and non-pharmacological interventions. Using Good planning will result in avoiding redun-
analgesics to relieve short-term procedural pain dant and unnecessary blood sampling. Care
in newborns is questionable because of these should be taken to avoid other routine care
agents’ poor effectiveness and potential side before a prick. Baby should be well swaddled

Journal of Neonatal Surgery Vol. 2(2); 2013

 Pain Relief in Neonates

and preferably held by the mother. If situation glare of procedure lamps. After the procedure
allows, procedure should be done during or af- baby should be held and comforted till all cues
ter a feed. Eyes should be shielded from the of pain have disappeared.

Table 2: Neonatal Pain Management Guidelines (for babies 27-44 weeks GA)

Procedure Supportive Oral Morphine Paracetamol Local Remarks

(where sucrose anesthesia
applicable)
NGT/OGT insertion Sw √
Venepuncture/IV Sw, NNS, BF √
cannulation
IM/SC Sw, NNS, BF, √
injections/vaccinations SSC
Heel prick Sw, NNS, BF, √
SSC
Plaster removal Sw, NNS, BF, Use adhesive
SSC remover
Dressing change Sw, NNS, BF, √
SSC
UVC/UAC Do not clamp
or stitch skin
Arterial puncture/line Sw, NNS, BF √
PCVC Sw, NNS √
Lumbar puncture √ EMLA Use max 1g
per
procedure
ET suction √ bolus
Elective ET intubation √ bolus 0.1mg/kg
only in
presence of
doctor
ROP screen/eye exam Sw, NNS, BF √
ICD insertion √ bolus
Post-op laser/caput √ Q4-6H
pain
Post hernia repair √ Q4-6H
Post-op Major surgery √ infusion At least 72
hours post-op
Suprapubic tap NNS √
Mechanical ventilation Consider
phenobarb.
Morphine on
case by case
basis
Bladder NNS √
catheterization
Suture removal NNS √
Sw: swaddling; NNS: non-nutritive sucking; SSC: skin to skin contact; BF: breast feeding
Oral sucrose: Maximum 8 times in 24 hours and three times per procedure. Do not use on babies who are sedated or have
poor suck. Do not use for pacifying or settling baby. Local anesthetic: EMLA cream to be used cautiously in G6PD deficiency.

Reference: Adapted from Lago P, Garetti E, Merazzi D, Pieragostini L, Ancora G, Pirelli A, et al. Guidelines for procedural pain
in the newborn. Acta Paediatr. 2009;98:932-939.

Procedural pain relief: babies to combine the synergism of non-nutri-

1. Non-nutritive sucking: [29] Using a pacifier tive sucking with sucrose analgesia [35].
would not be a feasible option in India because
of the obvious disadvantages. Pacifiers are 2. Breast feeding: Babies in a comfortable
dipped into sucrose solutions and given to position in the mother’s arms and breast feed-
ing showed a statistically significant difference
Journal of Neonatal Surgery Vol. 2(2); 2013
 Pain Relief in Neonates

in the duration of crying during and after im- 6. Arterial or venous blood sampling
munization [33]. This has potential for use in 7. Suctioning (i.e. nasal)
well babies especially in immunization clinics. 8. Urinary catheterization
9. Suprapubic tap
3. Swaddling: or facilitative tucking of the 10. NG/OG insertion
infant ensures smooth execution of procedure 11. Dressing change
but this is feasible only in certain infants and 12. Immunization
also depends on the procedure. Blood drawing 13. ROP exam
from extremities would benefit by tucking [36]. 14. Chest tube insertion/removal

4. Kangaroo care: Gray et al [37] found that 10– Principles:

15 minutes of kangaroo care reduced crying,
grimacing, and heart rate during heel-stick 1. 24% sucrose water when placed in the
procedures. Johnston et al showed that mouth, induces endogenous opioid production
kangaroo care significantly reduced the acute providing analgesia for minor procedures
pain responses of preterm neonates at 32–36 2. Do not use more than 3 doses during a
weeks’ and 28–32 weeks gestation [38]. single procedure
3. Do not use for infants requiring ongoing
5. Oral Sucrose; Oral sucrose and other sweet pain relief (e.g. postoperative), since these in-
tasting solutions have been used to promote fants will require acetaminophen or an opioid
calm and to reduce pain in infants over the such as fentanyl or morphine.
past century, and even before this time. In 4. It is important to realize that although an
1991 Blass [39] reported that 2mL 12%sucrose infant may still cry and show signs of pain
compared with 2mL water significantly reduced when 24% sucrose water is used, studies have
crying time during heel prick and circumcision. consistently shown that the sensation of pain
The underlying mechanism of the analgesic ef- and its negative effects will be diminished.
fects of sweet tasting solutions is considered to 5. Analgesic effect of 24% sucrose water
be due to an orally mediated release of endoge- appears to be less effective after 46 weeks post
nous opioids. Calming effects were shown to be conceptual age.
due to sweet taste, and not volume dependent,
as small volumes of 0.2 mL sucrose were Dosages: ONLY oral administration/dose
equally as effective as larger volumes of 0.6 mL
and 1.0 mL. The effects of sweet taste peak at 1. Intubated infants: 0.1ml
two minutes following administration, and per- 2. Infants < 1000 grams: 0.1ml
sist for around five to eight minutes [40] and 3. Infants <= 28 week gestation: 0.1ml
are dependent on contact with the tongue, and 4. Infants >= 1000 to 2000 grams: 0.1-0.2ml
not sweet ingestion directly via a nasogastric 5. Infants >= 2000 grams: 0.1-0.5ml
tube [41]. Despite a large number of studies the
mechanism of sweet taste and pain protection Procedure:
is unclear. 1. Using a 1ml sterile syringe or a dropper,
draw up desired dose, place tip of sy-
Guidelines for using oral sucrose in neonates ringe/dropper into the infant’s mouth onto an-
terior portion of the tongue and dispense solu-
Indications for use: Any short-term procedural tion slowly, allow the baby to savour the sweet-
pain ness.
2. Wait 2 minutes and then perform inter-
1. Intravenous access vention
2. IM injection 3. For infants requiring occasional sucrose
3. Tape removal doses, nurse may draw dose directly from con-
4. Lumbar Puncture tainer (discarding when procedure is com-
5. Minor suturing pleted).

Journal of Neonatal Surgery Vol. 2(2); 2013

 Pain Relief in Neonates

4. If giving more than 0.1ml, it may be best to prolonged time for onset of action. For elective
give a portion of the dose 2 minutes prior to the planned procedures e.g. lumbar puncture, cir-
procedure, and then the remainder of the dose cumcision, intravenous lines, arterial lines,
intermittently, throughout the procedure. where more than 60 minutes time is available,
EMLA cream is helpful. Interestingly, EMLA
Contraindications: cream is not useful in heel prick pain [44]. An-
esthetic eye drops in combination with oral su-
Use of 24% sucrose water is contraindicated in crose have been tried for reducing pain during
the following infants: retinopathy of prematurity (ROP) screening.

1. Infants at high risk for NEC Regional anesthesia

a. Asphyxiated infants
b. Infants with congenital heart disease This may be used appropriately e.g. dorsal pe-
that are not on established feeds nile block for circumcision if there is sufficient
c. Infants with feeding intolerance knowledge of techniques and dosages of various
d. Infants without bowel sounds agents [45].

2. Infants with esophageal atresia or tracheal Peri-operative pain relief

esophageal fistula
Millions of newborns undergo surgery for vari-
3. Infants who are sedated or on other pain ous conditions around the world every year.
medications that are at risk for aspiration Pain interventions must plan for intra-operative
4. Post-op infants who need to avoid excessive and post-operative periods. Potential drug ther-
saliva production apeutic groups include opioids and opioid an-
tagonists, sedatives/hypnotics, vapor anes-
5. Infants with active phase PPHN thetics, local anesthetics, or NSAIDs, and there
Documentation: is opportunity to combine multiple types of an-
algesic intervention
1. Document on nursing flowsheet/medication
area the amount and # of doses used. Opioid analgesics

2. Assess pain score using a suitable scale Morphine: This is useful for moderate to severe
before, during, and after the procedure docu- acute pain, for pre-operative sedation, and
menting on the nursing flowsheet. during anesthesia. Morphine and its metabo-
3. Repeat doses may be administered during lites are cleared by the kidneys and partly by
single procedure if indicated by pain score, not biliary excretion. It is administered usually by a
exceed 3 doses. continuous infusion of 10-30µg/kg/hour in
ventilated neonates for perioperative pain relief
Concomitant use of various non-pharmacologi- [46]. Neonates, especially preterms are more
cal techniques achieves greater clinical effec- sensitive to opioids and are at risk for apnea,
tiveness than any one of these techniques used hypotension and urinary retention.
alone
Fentanyl: This is a synthetic opioid that is 50-
Local anesthetics 100 times more potent than morphine. The
main side effects are apnea, bradycardia and
Cutaneous infiltration of lidocaine or other local
chest wall rigidity. In ventilated neonates both
anesthetics treats pain from skin-breaking pro-
morphine and fentanyl infusions produce evi-
cedures like lumbar puncture, ICD insertion,
dence of physiological pain relief but may pro-
for about 60-90 minutes [42]. EMLA cream
long ventilation [47].
(eutectic mixture of local anesthetic) has been
used for circumcision but studies have shown Others: Remifentanil and alfentanyl have been
that it is effective but inferior to dorsal penile used for short procedures like tracheal intuba-
nerve block [43]. Disadvantage includes the
Journal of Neonatal Surgery Vol. 2(2); 2013
 Pain Relief in Neonates

tion or placement of central lines but safety 10. Schulte FJ. Neurophysiological aspects of brain
development. Mead Johnson Symp Perinat Dev Med.
data are lacking in neonates [48]. 1975; 6:38-47
11. Gilles FJ, Shankle W, Dooling EC. Myelinated tracts:
Non-opioid analgesics growth patterns. In: Gilles FH, Leviton A, Dooling EC,
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Acetaminophen: (paracetamol) is often pre- epidemiologic neuropathology. Boston: John Wright,
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12. Slater R, Cantarella A, Gallella S, Worley A, Boyd S,
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brain. Pain. 2006;122:109–17.
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14. Wong CM, Boyle EM, Stephen RI, Smith J, Stenson
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CONCLUSIONS 15. Taddio A, Shah V, Shah P, Katz J. Beta-endorphin

concentration after administration of sucrose in
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Address for correspondence

Lalitha Krishnan,
Department of Pediatrics, Pondicherry Institute of Medical sciences
E mail: [email protected]
© Krishnan L, 2013

Submitted on: 28-02-2013

Accepted on: 12-03-2013
Published on: 01-04-2013
Conflict of interest: Nil
Source of Support: Nil

Journal of Neonatal Surgery Vol. 2(2); 2013