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Pain – INFANT
______________,2013
updated: 4/5/2014
FT, PT, Review of non-pharmacologic strategies to reduce pain, KC and BF
reduce pain and says that parental involvement in pain reduction is important.
Abdel Razek et al., 2009 FT, infants in 1st year of life who got maternal KC +BF (n=60) or standard clinic
(n=60) immunization. Sig shorter duration of crying during and after injection in
KC + BF group. HR lower and less variability in KC. Lower NIP score. Not
RCT because did not randomize to groups.
Acad BF Med2010
Coordinating breastfeeding with pain is best to reduce pain, but KC is 2nd
best
Akcan et al., 2009
PT, RCT PIPP scores lower in 25 maternal KC infants
(30 mins before and 10 mins after invasive procedure –but not during the
procedure) during and after procedure compared to 25 controls
AAP/CanadPedSoc, 2006
Policy. Recommends KC for pain reduction with neonates
Anand et al., 2006
PT, FT, Summary of proceedings from consensus group meeting. KC is one way
to treat procedural pain and is recommended by this group.
Anand, 2008
Review, concerns about infant pain have led to the development of nonpharmacologic therapies such as sucrose, massage and kangaroo care for
neonatal pain,
Ancora, 2010
PT, Review, pain control is essential to make NICU developmentally
appropriate
Axelin- See axelin below
Bakewell-Sachs et al ‘03
Review of pain management, more research on pain management strategies
needed
Batton et al 2006
Bauer K , 2005
PT aap & cps recommend kc to reduce pain
PT review, KC is a time when infants are protected from painful interventions
Bulfone et al 2011
PT and FT review of 19 articles - some show that KC reduces pain
Bunik et al., 2010
PT,FT., policy of combining breastfeeding and KC to reduce procedure pain
Burkhammer et al 2004
FT, case study, kc reduces nipple pain
Byaruhanga et al 2008
FT, qualitative, 5 focus groups, moms reported that KC distracted them from
post delivery pain (episiotomy and contractions)MATERNAL PAIN
Bystrova 2009
Review of physiology of the C-Afferent nerves which is a second tactile system
and the pleasant touch that stimulates the c afferent nerves release oxytocin and
oxytocin reduces pain, - a physiologic KC mechanism
Canadian Ped Soc 2012
PT, Position statement that says that KC reduces pain and it proposed that this is
done through sensory saturation and says that KC should be used for bedside
painful procedures for preterm infants.
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Campbell-Yeo etal. 2009 PT, RCT. of cobedding skin to skin in 128 twins because skin to skin between
mom and baby reduces pain. This is abstract of what is planned, not what has
been done. NOT A KC STUDY yet
Campbell-Yeo et al 2011 Review of mother-driven pain interventions. KC reduces pain perception; other
strategies do too. Mother’s presence is very important for pain reduction.
Campbell-Yeo et al., 2013 PT Proposal of three group comparative study of repeated use of KC alone, 24%
sucrose alone, or KC+sucrose for procedural pain in NICU. PIPP for pain,
NAPI for neurobehavioral develop at term age and cortisol being measured.
Carbajal et al., 2004
Review of pain. Same as 2005 publication but in English. Describes pathways
by which KC may directly and indirectly affects pain response. MECHANISMS
Carbajal et al., 2005
Review of pain management strategies and reviews Gray and Johnson’s articles
and states that skin to skin contact is a part of BF and provides the direct (by
blocking nociceptive transduction or transmission or activation of descending
inhibitory pathways or by activating attention and arousal systems that modulate
pain (pg. 114) and indirect mechanisms (reduce total amount of noxious stimuli
to which infants are exposed) of how SSC reduces pain. MECHANISMS
Carbajal et al., 2008
Review that says infants do not get relief from procedural pain
Castral et al., 2008
PT, RCT of 15 min of KC before, during and after heel stick. Facial coding less
in KC group, and less heart rate increase and less behavioral state agitation in
KC group.
Castral et al. 2012
PT, correlational, infant’s HR and salivary cortisol pain responses to heel stick
were influenced by mother’s ability to regulate her own stress (maternal salivary
cortisol level) but mother’s depression and anxiety did not affect infant pain
response. This is also a CO-REGULATION STUDY
Celeste et al 2008
Very PT, Randomized cross over trial, kc diminishes heel lance pain
MICROPREEMIES
Chermont et al., 2009
FT, RCT, KC is effective to reduce pain, and when added to oral 25% dextrose
it acted synergistically to reduce pain even more. Hepatitis B vaccination given
Chidambaram, 2013
PT, RCross over of KC that reduced pain better than no KC group.
Childrens Hosp Philly2007
PT, should document pain score during ventilated KC for all infants
Chroma &Sikorova 2012 Review of non-pharmacologic methods of pain reduction and KC comes in
second to nutritive sucking and works better when combined with other nonpharmacologic methods. See also Johnston Cochrane of 2012 and 2014
Cignacco et al.,2007
Review of non-pharmacologic interventions and mentions that KC appears to be
effective and should be used to minimize pain.
Cignacco et al. 2008
NOT A KC STUDY. RCT of morphine and MSS (multisensory stimulation =
nurse massages baby’s face and back, gently talk to baby, and put vanilla oil on
nurses hands during massage for orogustatory stim and sucrose on cotton stick
in baby’s mouth for sucking. Neither morphine nor MSS after endotracheal
suctioning eased pain. So comparing parts of maternal like experience to
morphine for pain reduction did nothing. Similar to Johnston’s maternal voice
study. Cignacco E, Hamers JP, van Lingen Ra, Zimermann LJI, Muller R,
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Gesler P. Nelle M. Pain relief in ventilated preterm infants during endotracheal
suctioning: a randomized controlled trial. Swiss Med Weekly, 2008, vol 138
#45-44, pg. 635-645. SIMULATED KC
Cignacco et al., 2009
NOT KC, but is REPEATED heel sticks (over days) study with sucrose.
Clifford et al., 2004
FT, Review article, KC effectively reduces fullterm infant pain and is
recommended as a pain reduction intervention.
Cong et al., 2006
PT, heel stick in KC and then in incubator or vice versa. Much less pain as
measured by PIPP when received 30 minutes of KC and heelstick in KC than in
incubator. Heart rate variability and SaO2 better with KC heelstick.
Cong et al., 2009
PT, randomized cross over of 60 min of KC before KC heelstick vs 60 mins of
incubator before incubator heelstick. Lower HR rise during heelstick in KC and
and lower HR during KC baseline. Many HRV changes too. More stable
autonomic functioning with KC heelstick.
Cong, L-Hoe et al., 2011 PT, Randomized cross over trial of 80 and 30 minutes of KC on Cortisol and
PIPP. Babies had less pain in KC heelstick than incubator heelstick, regardless
of sequence.
Cong et al 2012
PT, case study, 28 weeks, KC and heel stick, infant had better outcomes when
they had KC for 15 or 30 minutes in comparison to incubator but no difference
in PIPP between KC for 15 minutes to KC for 30 minutes. DOSAGE STUDY
Cong, et al. 2012
PT randomized cross-over trial of 15 and 30 min of KC vs incubator on heart
rate variability, both longer and shorter periods of kc stabilized autonomic
control during pain better than incubator
Cong & L-H, 2013
PT, FT, ergonomic step by step procedure for personnel to conduct
venipuncture and injections during KC
D’Apolito, 2006
Review, cortisol and B-endorphin level were significantly reduced for infant in
KC, thus MECHANISMS
deSousa Freire et al., 2008 PT, RCT of 3 groups. KC group had lower PIPP, less variation in HR and SaO2
and shorter duration of facial action with 10-15 min of KC before and during
stick than incubator alone or incubator + oral glucose groups. Same as Freire
ref.
Dodds, 2003
PT, Survey of nurses- RNs don’t use pharma treatments because they think that
they are harmful to infants. We need non-pharmacologic interventions
Ferber & Makhoul 2008
PT, R cross over. NIDCAP signs of neurobehavioral stress were less with heel
stick when heelstick was done in KC than in an incubator. Randomized crossover design. Got 15 mins of KC.
Freire et al., 2008
PT, RCT, see de Sousa Freire above. Same article. This is the one that pubmed
uses, but the words “de Sousa” appear in actual article, not pubmed citation.
Gibbins et al.2008
PT, Review of universe of developmental care and how KC is listed in the
comfort care planet because Kc reduces pain.
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Golianu et al., 2007
Review of non-pharmacologic techniques and mentions that KC should be used
to alleviate acute pain, but cannot provide analgesia for moderate or severe pain
in neonate. KC needs to be included in a graduated multidisciplinary algorithm
for pain management.
Gray, Watt, Blass 2000
FT, RCT, 10-15 min KC B4 heelstick, KC heelstick vs. swaddled in crib B4 and
During heelstick. HR increased 8-10 (KC) vs 36-38 (C), crying time dropped
82% KC, facial grimacing dropped 64% KC. Not opioid mediated but pain
blockade. Effects of KC seen once infant had relaxed in KC and that took 15
mins.
Gray et al., 2002
FT, mat KC & simultaneous BF (two minute baseline before stick) reduced
pain response as compared to cot heel stick.
Hall, 2012
PT, Review. Pain is undertreated, common, and has adverse effects and most
common non-pharmacologic treatments are nonnutritive sucking with/without
sucrose, KC, swaddling and massage.
Hall & Kirsten, 2008
PT, study of # of kc vs incubator infants who needed blood transfusions. The
article ends with a Review of lit that says KC reduces pain.
Hardy 2011
FT, PT, Review, KC reduces pain, in KC a combination of enzymes &
hormones are released and raise pain thresholds . KC reduces behavioral
response to pain
Hardy,2011
FT, review of L-H’s Developmental Care chapter and relates that. KC reduces
pain.
Harrison et al 2010
PT, FT review, kc mentioned on 118-119. In all studies KC reduces pain, kc is
Better than sucrose, enhanced KC with rocking etc did not have more benefits,
more research is needed to study kc on pain, policies for use of KC for all nonemergency for pain situation needed
Hensel, et al. 2013
FT, PT, Review of pain relief strategies for newborns. Says KC is effective and
KC can be combined with sucrose to alleviate pain.
Hung and Berg 2011
FT, one mother said “when they put the baby on my arms I forgot about the
pain” during cesarean birth
Hunseler & Roth, 2008
PT, FT Review of pain strategies and states that KC is effective in reducing
Pain in fullterms and preterm.
Johnson 2005
Review for Advanced Practice Nurses use of KC and cites that KC reduces pain
Johnston et al., 2003
PT. Heelstick pain decreased PIPP by 2 points in 30 mins of KC heelstick
vs.incubator. Some infants did not cry at all during the KC heelstick
Johnston, Nuyt ,2007
PT, heelstick pain did NOT decrease on PIPP when infants heard recording of
filtered mother’s voice. The skin-to-skin modality of maternal presence is
needed to blunt pain response to heel stick. SIMULATED KC
Johnston et al., 2007
PT, FT, review in text. Says effects of fathers on reducing pain has not been
studied.
Johnston et al., 2008a
PT, VLBW, RCT, less pain and faster recovery in KC (10-15 mins) than
incubator
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Johnston et al., 2008b
Johnston et al 2010
Johnston et al 2014
PT Rcross over of KC +singing, rocking, sucking and then KC alone. No diffs in
pain relief between two conditions. KC alone is sufficient to decrease pain
response.
PT, FT first report of planned Cochrane analysis for kc pain reduction
PT, FT, completed pain Cochrane and shows that KC reduces pain
Johnston et al.,2011
PT R cross over. Maternal KC reduces pain perception better than paternal KC.
MAT vs PAT
Johnston et al. 2011
Rev of pharmacologic interventions and says that KC will be reviewed in part 2
which is under Campbell-Yeo et al., 2011.
Johnston, F, C-Y, 2011
Physiology of pain review in Pain. Pertains to PT and FT infants
Johnston, Byron et al. 2012 PT, R cross over of 18 preterms 15 mins of KC with mom one day and 15 mins
of nurse KCing on other day before heel stick. Surrogate woman not as good as
maternal KC.
Johnston et al. 2014
Jonson et al 2004
PT, FT, Cochrane meta-analysis shows that KC reduces pain.
review, research shows that KC reduces pain responses
Kashaninia et al., 2008
FT, RCT, less NIPS pain and less crying with 10 min of mat KC (+2 min during
shot) than in crib
Klaus 2009
review, oxytocin release during kc reduces pain MECHANISM
Klaus & Klaus, 2007
A preface review that states that KC increases oxytocin production which in turn
raises the pain threshold. This is a mechanism of KC’s impact on pain.
MECHANISM
Kostandy et al., 2008
PT, descriptive, 30 mins of KC + KC heelstick cut audible and inaudible crying.
Kostandy & GCA 2003
FT. RCT Some KC infants did not cry at all during hepatitis shot. See 2013 ref.
Kostandy 2005
FT, Dissertation results: KC reduced infant crying during Hepatitis C vaccine
Kostandy & LH 2012??
FT, case report of how one newborn girl responded to two heelsticks and one
shot given in cluster and used pretest-test-posttest design. HR, behavior state
(sleep) and crying all improved with KC during the clustered procedures.
Kostandy et al. 2013
FT, RCT of KC for Hep B vaccine injection and KCers had less crying during
injection and recovery and returned to calm state sooner than controls. Heart
rate trended to being lower during injection in KCers than in controls.
Lago et al., 2009
Review, recommends KC to manage procedural pain
Leslie & Marlow, 2006
PT, FT Review of non-pharmacologic pain relief measures. Reviews studies
Showing that KC reduces pain responses in preterm and fullterm infants.
Lindgren et al. 2011
Descrip. Study that showed that human skin-to-skin touch (without movement)
is a pleasant sensation and that skin to skin touch with movement (massage) is
an even stronger pleasant sensation and that touch with or without movement
most strongly activates the pregenual anterior cingulate cortex, an area that
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when activated (usually by opioid analgesia or by oxytocin) reduces pain,
anxiety, stress and increases sense of well-being..
Lisle-Porter 2009
Clin article about dying babies and it says to do KC to keep parents involved
and reduces stress/pain (see Lindgren above) – this is all in the table, not in the
text. PALLIATIVE CARE
Long 2010
Commentary on Chermont 09 study and agrees that kc with sucrose may be
Better than KC alone
Ludington-Hoe 2011
Review, kc reduces pain
Ludington- Hoe 2011
30 years of review, kc reduces pain
Ludington, 1994
PT, descriptive crossover of 3 hr KC then KC Heelstick then 3 hrs incubator
with incubator heel stick. Crying time was 5 seconds with KC heelstick; 45
seconds in Incubator heel stick.. Abstract of El Salvador study.
Ludington-Hoe et al. 2005 PT R cross over. Crying time was sig. less during 2-3 hours of KC + KC
heel stick than incubator. 3/11 infants did not cry at all with KC heelstick. HR
did not rise as much in KC. Big SECTION ON MECHANISMS
Ludington-Hoe et al.’08
PT, national USA guidelines recommend KC for pain reduction and reviews all
studies to March 2008
Lundberg 2009
skin to skin contact provides analgesia
Mallet et al., 2007
Descriptive study of French health professionals knowledge and use of KC.
Pain effects of KC were not known by anyone.
Marin Gabriel 2009/2010 FT no difference in episiotomy pain between birth kc and no KC
Marin Gabriel, et al. 2013 FT, RCT of KC+BF, KC+Sucrose, KC alone and sucrose alone showed KC+BF
far superior to others in reducing pain and crying to heel stick. No effect on HR.
McGrath JM 2006
Editorial that states that family presence during procedures is needed and should
be followed, and states in Guideline #3 that parents be encouraged to “..touch
and sooth infants.” Does not mention KC per se, but talks about touch and
presence.
McGrath & Brock, 2002 Review. Recommends KC for pain reduction and says after lit review that
nurses do not use it for this reason.
Meek & Huertas, 2012
PT, FT, Cochrane meta-analysis that shows that KC reduces pain and does it
better than swaddling and facilitative tucking. This is the study that talks
about Fabrizi’s work about KC handling the brain’s pain better than
sucrose which just eradicates behavioral signs of pain, and does not
eradicate brain memory and pathways for long term adverse effects of pain
like pleasing human touch can do. FABRIZI
Merenstein & Gardner 2002 Text book, KC is a good analgesic
Messerer et al.,2014
PT,children adolescent Review of non-pharmacologic pain treatments. KC can
be used for slightly painful procedures More research needed for its
effectiveness in children.
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Miles et al., 2006
Mitchell et al. 2013
Morelius et al., 2005
PT, RCT, vlbw, daily KC for 4 wks starting in 1st week, 20 mins of KC each
time. Pain profile at 4 and 12 months during an immunization; no difference
between grps (KC vs. non-KC) on pain response at 4 and 12 months (standard
care), but did not get KC during immunization at 4 and 12 months. Long term
effects of KC, but did not get KC during pain procedures in hospital either.
PT 2 studies address pain
PT. Used PIPP to measure pain/discomfort during 1 hours of KC. Found first
session of KC was more stressful/behaviorally agitating than 4th session of KC.
Montirosa et al,, 2013
PT, quasi-exp, maternal stress was related to infant’s pain
Morrow et al 2010
FT, RCT, not KC held full upright swaddled reduced pain than in crib
Nanavati et al., 2013
PT, RCT, VLBW 50 infants got either KMC or expressed breast milk for pain
reduction with adhesive tape removal. No differences in PIPP Pain scores after
removal of the tape between the groups.
NANN, 2008
2nd Edition of Pain Assessment and Management Guidelines that includes KC
for procedural pain management.
Naughton 2005
Review. Says KC can be used to reduce pain.
Nimbalkar et al. 2012
PT, RCT cross over of 15 mins of KMC in 50 preterms 32-36 wks GA who had
heel stick. HR, behavior, facial scores, PIPPs were 4.85 lower in KMC, but
SaO2 did not differ between groups. PIPP was 4.85 points lower.
Nyqvist et al., 2010
Universal article, Recommendations from 7th INK meeting. Says that KMC
reduces pain and cites Johnston’s studies.
Okan et al 2010
FT, RCT, kc with breastfeeding group, kc group, and control group. no
differences in the kc with breastfeeding and kc only
Parsons et al, 2010
functional neuroanatomy of newborn review page 229 says skin-to-skin has
analgesic effects and mechanism is sensory saturation (simultaneous multi
senses stimulation) . MECHANISM
Pillai Riddell et al. 2011
FT, PT, Cochrane review of pain management in infants and says that maternal
presence reduces use of pain medication and reduces pain of infant.
META=ANALYSIS Also, did standardized mean differences and found that
KC mean differences in reduction of pain were greater than what they were for
facilitated tucking and any other non-pharmacologic pain relief strategy.
Saeidi et al., 2011
FT, Quasi-experimental but random assignment to 2 min of Kc before
vaccination and 3 mins Kc after vaccination. study of videotaped pain and
crying time. Pain significantly less in KC group,
Sajedi et al., 2007
FT, RCT of 10 minutes of KC before, during and after injection. Mean HR was
lower and mean SaO2 was higher in the KC infants than in no-KC infants.
Schultz et al, 2009
PT survey of 33 NICU doctors who knew that breastfeeding and sucrose affect
pain but a fewer number knew about kc effects
Shah 2006
Cochrane review. Says BM is not as good as sucrose in reducing HR and pain
responses. NOT KC study
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Shah & Jefferies, 2012
PT, Commentary on Johnston 2011 study in which infants having heel lance
have lower pain scores and quicker time to return to baseline HR when held in
KC by mom than by father. MAT vs PAT
Stevens and Franck, 2001 Review. Say further investigation of KC as a potential source of analgesia in
human neonates is most certainly warranted
Stevens et al. 2004
PT, Cochrane review and at end says Sucrose should be tested with KC
Stevens et al., 2007
PT, FT, review in Text. Reviews Johnston’s study and then says the
effectiveness of KC in reducing procedural or chronic pain in unstable and
vulnerable infants requiring multiple supportive therapies has not been
established.
Suresh et al 2009
Not a kc study, lay review that shows massage reduces pain
Terhaar & Starr, 2007
A review for physicians revealing that KC should be routine practice but is not,
reviews all “strong” literature supporting KC and gives docs a test at end so it is
a continuing education offering too. Cites pain reduction.
Thiel &Ostermann, 2010 Systematic review of pain studies and concludes that KC is simple and effective
method to reduced mild to moderate pain in neonates.
Torowitz et al 2010
FT, Case report, congenital heart disease newborn, kc reduce pain measured by
FLACC
Tsao et al., 2007
PT,FT review says KC is natural, non-invasive analgesic, gives good
identification of research limitations, says it has effect through state and
maternal touch, and that further research on generalizability and maternal
attitudes is warranted.
Tsao et al., 2008
PT,FT, review, part two that reviews KC (part 1 reviewed sucrose and NNS) and
KC studies are reviewed on pg 402 and on pg. 405 says KC is an appealing
method.
Uvnas-Moberg 2003
book, cites studies about oxytocin releases during kc in neonates MECHANISM
Uvnas-Moberg 2005
Review, oxytocin released during KC increases pain threshold MECHANISM
Van Sleuwen et al. 2007
Review of 78 swaddling studies. Swaddling is not as good as KC for pain
reduction
Vivancos et al, 2010
FT, quasi- experimental, neonates did not cry during the hep B shot (put this
study in the new study discussion, they said that babies did not cry at all during
the injection while all my babies did cry).
Walden & Jorgansen 2010
book chapter review, kc decreases pain response to heel stick
Walter-Nicolet et al 2010
FT and PT review, kc reduces pain response, breastfeeding
Walter et al 2007
FT descriptive , kc distracted mother from episiotomy repair
Warnock, et al., 2010
Review, systematic narrative review of 12 KC and pain studies and said could
not do meta-analysis because no standard errors were reported. They call for
better descriptions of KC, use of a guiding framework, better explanation of
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study methods and analyses, and reporting effect sizes, but conclude that KC is
safe and effective method to reduce mild to moderate pain in neonates.
Yamada et al., 2008
Review of systematic reviews. KC is a holding technique that was in systematic
reviews. States that more research is needed on single, repeated, and
combined pharm and non-pharm interventions, including KC.
PAIN – MATERNAL
Axelin et al.,2010
Byaruhanga et al. 2008
Johnson 2005
Marin et al., 2010
Henderson, 2011
Hung and Berg 2011
Lindgren et al. 2011
Walters et al. 2007
Svenson et al., 2013
Not KC, but a study of maternal attitude on holding to reduce pain, some do
some do not want to hold, but holding is better than sucrose
FT. qual.study: Moms felt that Kc distracted them from episiotomy repair
PT review. Recommends testing KC on maternal pain effects
FT, RCT of birth KC, no difference in episiotomy pain between groups
FT. KC during C/S and cites Walter’s study for decreased sensations during
surgery
FT, one mother said “when they put the baby on my arms I forgot about the
pain”
Not a KC study. Theory. Adult, human skin to skin massage is a pleasant
sensation even more so than just human skin to skin touch without movement
and that the skin to skin touch stimulates the pregenual anterior cingulate cortex,
an area that when activated by opioids reduces adults’ pain, anxiety, stress and
increase sense of well-being.
FT, Birth KC. Md’s reported that maternal pain management was better with
birth KC for episiotomy repair.
FT,RCT.maternal pain before and during breastfeeding was being measured
but no differences in nipple pain between kc+BF vs BF alone group were
evident.
MATERNAL vs PATERNAL ABILITY TO REDUCE PAIN
Johnston et al. 2011
Shah & Jefferies, 2012
PT, original article showing mothers are better at relieving pain
Commentary on Johnston et al. 2011 study
Related Literature
Andrews, K., & Fitzgerald, M. (1994). The cutaneous withdrawal reflex in human neonates: Sensitization,
receptive fields, and the effects of contralateral stimulation. Pain, 56, 95-101.
Arias MC, Guinsburg R.(2012). Differences between uni-and multidimensional scales for assessing pain in
term newborn infants at the bedside. Clinics (Sao Paulo). 2012 Oct;67(10):1165-70. This study sought to
determine the level of agreement between behavioral and multidimensional pain assessment scales in term
newborn infants submitted to an acute nociceptive stimulus.This cross-sectional study was performed on
400 healthy term newborns who received an intramuscular injection of vitamin K during the first 6 hours of
life. Two behavioral pain scales (the Neonatal Facial Coding System and the Behavioral Indicators of
Infant Pain) and one multidimensional tool (the Premature Infant Pain Profile) were applied by a single
observer before the procedure, during cleansing, during injection and two minutes after injection. The
Cochran Q, McNemar and kappa tests were used to compare the presence and degree of agreement between
the three scales. The Hotelling T2 test was used to compare the groups of newborns for which the scales
showed agreement or disagreement. A generalized linear regression was used to compare the results of the
Neonatal Facial Coding System and the Behavioral Indicators of Infant Pain across the four study time
points.The neonates studied had a gestational age of 39±1 weeks, a birth weight of 3169±316 g and and
postnatal age of 67±45 minutes. During the stimulus procedure, 80% of the newborns exhibited pain
behaviors according to the Neonatal Facial Coding System and the Behavioral Indicators of Infant Pain,
10
and 70% experienced pain according to the Premature Infant Pain Profile (p<0.001). The frequencies of the
detection of pain using the Behavioral Indicators of Infant Pain and the Neonatal Facial Coding System
were similar. The characteristics of the neonates were not associated with the level of agreement between
the scales.The Neonatal Facial Coding System and the Behavioral Indicators of Infant Pain behavioral
scales are more sensitive for the identification of pain in healthy term newborn infants than the
multidimensional Premature Infant Pain Profile scale.
Bartocci M, Bergqvist LL, Lagercrantz H, Anand KJ.(2006). Pain activates cortical areas in the preterm
newborn brain. Pain. 2006 May;122(1-2):109-17. Epub 2006 Mar 13. Neonatal Research Unit, Astrid
Lindgren's Children's Hospital, Karolinska University Hospital, Karolinska Institute, SE-17176 Stockholm,
Sweden. marco.bartocci@kbh.ki.se. To study the patterns of supraspinal pain processing in neonates, we
hypothesized that acute pain causes haemodynamic changes associated with activation of the primary
somatosensory cortex. Forty preterm neonates at 28-36 weeks of gestation (mean=32.0) and at 25-42 h
(mean=30.7) of age were studied following standardized tactile (skin disinfection) and painful
(venipuncture) stimuli. Changes in regional cerebral haemodynamics were monitored by near infrared
spectroscopy (NIRS) over both somatosensory cortices in 29 newborns, and over the contralateral
somatosensory and occipital areas in 11 newborns. Heart rate (HR) and peripheral oxygen saturation
(SaO2) were recorded simultaneously with NIRS parameters: oxygenated [HbO2], deoxygenated, and total
hemoglobin. Tactile stimulation produced no changes in HR or SaO2. HR increased in the first 20s
(p<0.001), while SaO2 decreased during the 40s after venipuncture (p<0.0001). Following tactile or
painful stimulation, [HbO2] increased bilaterally regardless of which hand was stimulated (p<0.0001).
Pain-induced [HbO2] increases in the contralateral somatosensory cortex (p<0.05) were not mirrored in the
occipital cortex (p>0.1). Pain-related [HbO2] increases were more pronounced in male neonates (p<0.05 on
left, p<0.001 on right), inversely correlated with gestational age (r=-0.53 on left, p<0.01; r=-0.42 on right,
p<0.05) and directly correlated with postnatal age (r=0.75 on left, p<0.0001; r=0.67 on right, p<0.0001).
Painful and tactile stimuli elicit specific haemodynamic responses in the somatosensory cortex, implying
conscious sensory perception in preterm neonates. Somatosensory cortical activation occurs bilaterally
following unilateral stimulation and these changes are more pronounced in male neonates or preterm
neonates at lower gestational ages.
Bergqvist LL, Katz-Salamon M, Hertegård S, Anand KJ, Lagercrantz H. (2009). Mode of delivery
modulates physiological and behavioral responses to neonatal pain. J of Perinatol. 2009 Jan;29(1):44-50.
Delivery mode needs to be monitored in future studies because physiological events associated with a
normal delivery reduce the physiologic and sympathoadrenal activation by nociceptive mechanisms. Pain
and stress reactivity appear to be inhibited during fetal life and sensory inputs during vaginal delivery may
reverse this inhibition. To minimize neonatal pain, we recommend that postnatal invasive procedures to be
performed shortly after vaginal birth (Bergqvist et al., 2009)
Brummelte S., Grunau RE, Chau V, Poskitt KJ, Brant R, Vinall J, Grover A,Synnes AR, Miller SP. (2012).
Procedural pain and brain development in premature newborns. Annals of Neurology 71(3): 385-396. 86
infants born 24-32 weeks were followed from birth with MRI, 3-dimensional MRspectroscopy imaging,
and diffusion tensor imaging. First scan at 32.1wks, scan 2 at term age. Calcuated N-acetylaspartate to
choline ratios , lactate to choline ratios, average diffusivity, white matter fractional anisotrophy from 7
white and 4 subcortical gray matter sites. Procedural pain was quantified as the number of skin breaking
events. After comprehensively adjusting for illness severity, morphine exposure, brain injury, surgery and
other factors, greater neonatal procedural pain was assoc with reduced WHITE MATTER and reduced
GRAY MATTER. Reduced WHITE MATTER was predicted by EARLY PAIN before scan #1; reduced
GRAY MATTER was predicted by pain exposure throughout the neonatal course. Early and continuing
pain reduces brain matter. Early procedural pain in very preterm infants contributes to impaired brain
development.
Butt ML & Kisilevsky BS. (2000). Music modulates behavior of premature infants following heel lance.
Can J Nurs Res 31(4), 17-39. 14 preterms 29-36 wks GA tested on 2 occasions, one with music and then
no music.videotaped for baseline, heel lance, and recovery and data separated according to two age groups
<31 wks pma and > 31 weeks pma. ANOVA showed that heel lance elicited a stress response (increased
11
HR, decreased SaO2, increased arousal, increased facial actions) in both age groups. STRESS reponse
greater in older infants. During recovery older infants had faster return on heart rate, behavioral state and
facial expression to baseline in the music group. Music is an effective stress reducing intervention.
Chik & Sluka. 2012. Massage and swaddling reduce pain in infants. Paper presented at American Pain Society,
31st Annual Scientific Meeting, May 16, 2012, Abstract 333 and 455. Cited in Ridky 2012 on KC bib
Fabrizi L, Slater R, Worley A, Meek J, Boyd S, Olhede S, Fitzgerald M.(2011) A shift in
sensory processing that enables the developing human brain to discriminate touch from
pain. Curr Biol. 2011 Sep 27;21(18):1552-8. doi: 10.1016/j.cub.2011.08.010.
Fabrizi L, Worley A, Patten D, Holdridge S, Cornelissen L, Meek J, Boyd S, Slater
R.(2011) Electrophysiological measurements and analysis of nociception in human
infants.J Vis Exp. 2011 Dec 20;(58). doi:pii: 3118. 10.3791/3118.
Fabrizi L, Slater R. (2012). Exploring the relationship of pain and development in the
neonatal intensive care unit. Pain. 2012 Jul;153(7):1340-1341. doi: 10.1016/j.pain.2012.03.013.
Slater R, Cornelissen L, Fabrizi L, Patten D, Yoxen J, Worley A, Boyd S, Meek J,
Fitzgerald M.(2010). Oral sucrose as an analgesic drug for procedural pain in newborn
infants: a randomised controlled trial. Lancet. 2010 Oct 9;376(9748):1225-32. doi: 10.1016/S01406736(10)61303-7.
Worley A, Fabrizi L, Boyd S, Slater R. (2012). Multi-modal pain measurements in
infants. J Neurosci Methods. 2012 Apr 15;205(2):252-7. doi: 10.1016/j.jneumeth.2012.01.009.
Fearon I, Kisilevsky BS, Hains SM, Muir DW, Trammer J 1997. Swaddling after heel lance: age-specific
effects on behavioural recovery in preterm infants. J Dev. Behav Pediatr 18(4), 222-232. 15 infants in two
age groups (<31 wks pma and >31 wks pma)
(Fernandez M, Blass EM, Hernandez-Reif, M, Field, T., Diego, M., Sanders C. 2003. Sucrose attenuates a
negative electroencephalographic response to an aversive stimulus for newborns. Dev Behav Pediatr 24,
261-266)
Fernandez,A., Campbell-Yeo, M. & Johnston, C.C. (2010 or 2011) Procedural pain management for neonates
using non-pharmacologic strategies: Part 1: sensorial interventions. Advances in Neonatal Care, 11(4), 235241. This speaks to how auditory and olfactory recognition are helpful in reducing pain and it also reviews
facilitated tucking, containment, swaddling, positioning,nonnutritive sucking and sweet solutions. These are
nurse driven strategies and they are grossly underutilized. This only says in the introduction that KC will be
reviewed in part2 which is published under Campbell-Yeo in 2011.
Fitzgerald, M. & de Lima, J. (2001). Hyperalgesia and allodynia in infants. In: Finley GA, McGrath, PJ. Eds.
Acute and Procedural Pain in Infants and Children. Seattle: IASP Press. 1-12. The more the number of
previous painful experiences, the more likely the infant is to have hypersensitization to pain (Andrews and
Fitzgerald, 1994;Fitzgerald nd de Lima, 2001). Hypersensitivity to pain is an inability to implement
inhibitory mechanisms, thus the infant demonstrates an exaggerated pain response to subsequent pain
experiences.
Franck L & Gilbert, R 2002. Review. Should test KC as a pain reducing strategy. Reducing pain during
blood sampling in infants. Clinical Evidence 7, 352-366.
12
Franck,L.S., Oulton, K., & Bruce, E. (2012). Parental involvement in neonatal pain management: an empirical
and conceptual update. Journal of Nursing Scholarship, 44(1), 45-54. Provides a new theory of the levels of
parental involvement in managing NICU infant pain and clearly states that parents see their” role as a VITAL
ROLE in which they want full involvement” (pg. 48) and to help with infant pain as much as possible, want to
be informed of painful procedure before it occurs and then help baby through painful procedure and even use
specific treatments like change diaper frequently, give sucrose, , pacifier, proper rest opportunities, more skill in
health workers for putting lines in, create calm surroundings etc (pg 49 chart).. They don’t want to be told that
they should wait outside. Page 48 relates the stages of parental involvement: 1. None (views infant comfort as
nurse or doctor’s role only, 2. Be Informed, 3. Be present, 4. Provide comfort by touch, voice, specific
comforting techniques, 5 Informant for NICU staff (tells staff what works for baby), 6. Active decision maker,
7. Advocate for infant – primary responsibility in partnership with clinical team
Gibbins S, Stevens B etal. 2008. Changes in physiological and behavioural pain indicators over time in
preterm and term infants at risk for neurologic impairment. Early Human Dev epub before print.
Gibbins S, Stevens B, McGrath PJ, Yamada J, Beyene J, Breau L et al., 2007. Comparison of pain
responses in infants of different gestational ages. Neonatology (former Biol Neonate) 93(1), 10-18.
Gibbins S, Stevens B, Beyene J, Chan PC, Bagg M, Asztalos E.(2008). Pain behaviours in Extremely Low
Gestational Age infants. Early Hum Dev. 2008 Jul;84(7):451-8. doi: 10.1016/j.earlhumdev.2007.12.007.
Epub 2008 Feb 19. A prospective crossover design with 50 ELGA infants from one Canadian tertiary level
NICU was conducted. Infants were assessed in random order during standardized painful (heel lance) and
non-painful (diaper change) procedures. Physiological (heart rate, oxygen saturation) and behavioural
(facial and body movement) indicators were continuously collected during 4 phases of the procedures.
Biochemical (salivary cortisol) indicators were collected immediately before and 20 min following the
procedures. Four facial actions (brow bulge, eye squeeze, nasolabial furrow, vertical mouth stretch)
increased immediately following the heel lance. There were no specific changes in physiological, body
movement or cortisol indicators following the heel lance. ELGA infants demonstrated greater body
movements during the diaper change, which may reflect immature motor coordination. No differences in
pain responses were found for infants born between 23-25 6/7 weeks GA and those between 26-28 weeks
GA. Similarly, no gender differences were found .
Gray L, & Michalska, K. 2004. Sucrose effect on infant metabolism. Paper presented at ICIS, Chicago,
Illl, April 2004. Sucrose results in decreased rate of metabolism dur to an average 10 bp. Decrement in
heart rate following sucrose taste.
Harrington JW, Logan S, Harwell C et al., 2012. Effective analgesia using physical interventions for infant
immunizations. Pediatrics, 129(5): 815-822) tested the 5 S’s (swaddling, side/stomach position, shushing,
swinging, and sucking) on 2 and 4 month old infants and resulted in decreased crying time and decreased pain
scores for infants getting immunizations. The addition of sucrose did NOT lessen pain scores or crying further
(given 2 ml water or 2 ml of 24% sucrose before immunization and either parental comfort or the 5 S’s after
immunization. The 5 S group had lower pain scores than parental comfort group and no diff between 5S’s with
water and 5 S;s with sucrose. Pain reduction from physical intervention was significantly greater than pain
reduction from sucrose alone. IMMUNIZATION
Johnston, C. (2011). Pain control in infants and young children. Pain Research and Management. 16(5):
320.
Johnston C, Barrington KJ, Taddio A, Carbajal R, Filion F.(2011). Pain in Canadian NICUs: have we
improved over the past 12 years? Clinical J of Pain, 27(3), 225-232.
Johnston, C.C., Fernandes, A.M., Campbell-Yeo, M. (2011). Pain in neonates is different. Pain 152(3
suppl): S65-S73. Doi: 10.1016/j.pain.2010.10.008 Pain processing and management in neonates,
especially preterm neonates, differs from older populations. In this review, a brief background on pain
13
processing in neonatal life, pain exposure in Neonatal Intensive Care Units (NICU), the consequences of
untreated pain, and the difficulties in treating procedural pain pharmacologically will be presented. A more
detailed review of non-pharmacological interventions for procedural pain in neonates will include sensory
stimulation approaches, oral sweet solutions, and maternal interventions. Some possible mechanisms for
the effectiveness of non-pharmacological interventions are offered. Finally, avenues of research into similar
interventions as adjuvant therapies or drug-sparing effects in older populations are suggested. THIS MAY
BE KC, GET AT SCHOOL. Variation in pain in neonates. Pain processing and management in
neonates, especially preterm neonates, differs from older populations. In this review, a brief background on
pain processing in neonatal life, pain exposure in Neonatal Intensive Care Units (NICU), the consequences
of untreated pain, and the difficulties in treating procedural pain pharmacologically will be presented. A
more detailed review of non-pharmacological interventions for procedural pain in neonates will include
sensory stimulation approaches, oral sweet solutions, and maternal interventions. Some possible
mechanisms for the effectiveness of non-pharmacological interventions are offered. Finally, avenues of
research into similar interventions as adjuvant therapies or drug-sparing effects in older populations are
suggested
Campbell-Yeo ML, Johnston CC, Joseph KS, Feeley N, Chambers CT, Barrington KJ(2012).
Cobedding and recovery time after heel lance in preterm twins: results of a randomized trial. Pediatrics.
2012 Sep;130(3):500-6. doi: 10.1542/peds.2012-0010. Epub 2012 Aug 27 Women’s and Newborn Health
Program, IWK Health Centre, Halifax, Nova Scotia, Canada. marsha.campbellyeo@iwk.nshealth.ca
Cobedding of preterm twin infants provides tactile, olfactory, and auditory stimulation and may affect pain
reactivity. We carried out a randomized trial to assess the effect of cobedding on pain reactivity and
recovery in preterm twin neonates.Stable preterm twins (n = 67 sets) between 28 and 36 weeks of
gestational age were randomly assigned to a cobedding group (cared for in the same incubator or crib) or a
standard care group (cared for in separate incubators or cribs). Pain response (determined by the Premature
Infant Pain Profile [PIPP]) and time to return to physiologic baseline parameters were compared between
groups with adjustment for the nonindependence of twin infants. Maternal and infant characteristics were
not significantly different between twin infants in the cobedding and standard care groups except for 5minute Apgar <7 and postnatal age and corrected gestational age on the day of the heel lance. Mean PIPP
scores were not different between groups at 30, 60, or 120 seconds. At 90 seconds, mean PIPP scores were
higher in the cobedding group (6.0 vs 5.0, P = .04). Recovery time was shorter in the cobedding group
compared with the standard care group, (mean = 75.6 seconds versus 142.1 seconds, P = .001). No
significant adverse events were associated with cobedding. Adjustment for nonindependence between twins
and differences in baseline characteristics did not change the results.Cobedding enhanced the physiologic
recovery of preterm twins undergoing heel lance, but did not lead to lower pain scores.
Latimer, M., Jackson, P., Johnston, C. & Vine, J. (2011). Examining nurse empathy for infant procedural pain:
Testing a new video measure. Pain Research and Management, 16(4), 228-233.
Maneyapanda SB & Venkatasubramanian, A. (2005). Relationship between significant perinatal events and
migraine severity. Pediatrics 116(4), e555-e558. Nociceptive neuronal circuits are formed during embryonic
and postnatal times, so insult during these periods may result in long term altercations to pain circuitry via
synaptic plasticity. One long term result is central hyperexcitability, which is assoc with migraines. 280
pediatric migraine patient records were reviewed. A significant relationship betw being an NICU patient and
having migraine medication existed but no relationship between patients who were not NICU patients. NICU
patients also had significantly earlier onset of migraines. Pain experienced as a neonate alters later experience
of pain (happens through neuronal plasticity and central hyperexcitability. Early pain experience can affect
subsequent pain syndromes and pain in neonates needs to be TREATED to avoid long lasting neuronal
alterations.
Milazzo W, Fielder, J., Bittel A, Coil, J., McClulre M, Tobin, P. and Vande Kamp, V. (20110. Oral sucrose to
decrease pain associated with arterial puncture in infants 3036 weeks’ gestation: a randomized clinical trial.
Advances in Neonatal Care, 1196), 406-411.
14
Ranger M, Johnston CC, Limperopoulos C, Rennick JE, du Plessis AJ. (2011) Cerebral near-infrared
spectroscopy as a measure of nociceptive evoked activity in critically ill infants. Pain Res Manag. SepOct;16(5):331-6. Review
Rao M, Blass EM et al., 1997. Reduced heat loss following sucrose ingestion in premature and normal
human newborns. Early Hum Dev. 48 (1-2), 109-116.
Rattaz et al., 2005. Scent of mother’s milk reduces pain response. Rattaz C,Goubet N, Bullinger A.
(2005). The calming effect of a familiar odor on full-term newborns. J Dev Behav Pediatr 26, 86-92. And
run pubmed on Goubet 2003 for her familiar odor (but was not mother’s milk).
Rennick, J.E., Lambert. S., Childerhose, J., Campbell-Yeo, M., Filion, F. & Johnston, C.C. (2011).
Mother’s experiences of a Touch and Talk nursing intervention to optimize pain management in the PICU:
A qualitative descriptive study. Intensive Critical Care Nursing, 27(3), 151-157.
Doi:10.1016/j.iccn.2011.03.005 Parents consistently express a desire to support their child and retain a
care-giving role in the paediatric intensive care unit (PICU). Qualitative data gathered as part of a PICU
intervention study were analysed to explore mothers' experiences using a Touch and Talk intervention to
comfort their children during invasive procedures.To describe how mothers experienced involvement in
their children's care through a Touch and Talk intervention and whether they would participate in a similar
intervention again. RESEARCH METHODOLOGY AND SETTING: A qualitative descriptive design was
used and semi-structured interviews conducted with 65 mothers in three Canadian PICUs. Data were
subjected to thematic analysis.The overarching theme centered on the importance of comforting the
critically ill child. This included being there for the child (the importance of parental presence); making a
difference in the child's pain experience; and feeling comfortable and confident about participating in care.
All but two mothers would participate in the intervention again and all would recommend it to others.
Giving parents the choice of being involved in their child's care using touch and distraction techniques
during painful procedures can provide an invaluable opportunity to foster parenting and support the child
during a difficult PICU experience.
Santos LM, Ribeiro IS, Santana RC.(2012). [Identification
and treatment of pain in
the premature newborn in the intensive care unit]. Rev Bras Enferm. 2012
Apr;65(2):269-75. This study aimed to analyze the parameters used by the nursing staff of a
public hospital in Bahia for pain assessment in premature newborns and to describe the
interventions used to relieve the pain. This is a qualitative descriptive study that was carried out
through semi-structured interviews with ten participants, in the period from December 2008 to
January 2009. The data were analyzed through content analysis. The results showed the use of
crying and facial expression as the clinical indications of pain premature newborns and that the
interviewed participants use, on a non-systematic basis, non-pharmacological measures in order
to ease this process. We suggest the introduction of pain as the fifth vital sign to be evaluated
and the use of scales, contributing to excellence and humane care.
Stevens BJ, Abbott LK, Yamada J, Harrison D, Stinson J, Taddio A, Barwick M, Latimer M, Scott SD,
Rashotte J, Campbell F, Finley GA; CIHR Team in Children's Pain. (2011). Epidemiology and
management of painful procedures in children in Canadian hospitals. Canadian Medical Assoc.Journal,
April 19 , 183(7): E403-E410,
Stevens and Franck, 2001 Review. Say further investigation of KC as a potential source of analgesia in
human neonates is most certainly warranted
Stevens BJ, Yamada J, Ohlsson A. 2001. Sucrose for analgesia in newborn infants undergoing painful
procedures. Cochrane Databae Systematic Reviews, #4,CD001069. “The use of repeated administrations of
15
sucrose in neonates needs to be investigated as does the use of sucrose in combination with other behavioural
(facilitated tucking, kangaroo care) and pharmacologic (morphine, fentanyl) interventions.” SUCROSE &KC
Uvnas-Moberg K, Bruzelius G, Alster P, Lundeberg T. 1993. The antinociceptive effect of non-noxious
sensory stimulation is partly mediated through oxytocinergic mechanisms. Acta Physiologica
Scandinavica, 149, 199-204. Non-noxious stimulation such as stroking, skin-to-skin contact, touch,
massage, and pleasant warm temperature causes a release in oxytocin which enhances the antinociceptive
effects of these treatments. This is in animal studies. ANIMAL STUDIES OF SKIN TO SKIN
Vinall J, Miller SP, Synnes AR, Grunau RE. (2013). Parent behaviors moderate the relationship between
neonatal pain and internalizing behaviors at 18 months' corrected age in children born very prematurely.
Pain. 2013 Jun 5. pii: S0304-3959(13)00292-3. doi: 10.1016/j.pain.2013.05.050. [Epub ahead of
print].Children born very preterm (⩽32weeks' gestation) exhibit greater internalizing (anxious/depressed)
behaviors compared to term-born peers as early as 2years; corrected age (CA); however, the role of early
stress in the etiology of internalizing problems in preterm children remains unknown. Therefore, we
examined the relationship between neonatal pain and internalizing behavior at 18months' CA in children
born very preterm and examined whether parent behavior and stress moderated this relationship.
Participants were 145 children (96 very preterm, 49 full term) assessed at 18months' CA. Neonatal data
were obtained from medical and nursing chart review. Neonatal pain was defined as the number of skinbreaking procedures. Cognitive ability was measured with the Bayley Scales of Infant Development II.
Parents completed the Parenting Stress Index III, Child Behavior Checklist 1.5-5, and participated in a
videotaped play session with their child, which was coded using the Emotional Availability Scale IV. Very
preterm children displayed greater Internalizing behaviors compared to full-term control children (P=.02).
Parent Sensitivity and Nonhostility moderated the relationship between neonatal pain and Internalizing
behavior (all P<.05); higher parent education (P<.03), lower Parenting Stress (P=.001), and fewer children
in the home (P<.01) were associated with lower Internalizing behavior in very preterm children, after
adjusting for neonatal medical confounders, gender, and child cognitive ability (all P>.05). Parent
Emotional Availability and stress were not associated with Internalizing behaviors in full-term control
infants. Positive parent interaction and lower stress seems to ameliorate negative effects of neonatal pain on
stress-sensitive behaviors in this vulnerable population. PARENT STRESS TOO!
Weller & Feldman, 2003 – KC contact is a form of touch that promotes infant self regulation and the
infant’s ability to moderate the effects of some risk (painful) factors. Serum cholecystokinin (CCK)
and opiod peptides might be going up (or whichever direction is beneficial) when in KC.
Weller A, Rozin et al. 2002 pituitiary thyroid axis and adrenal function in preterm infants raised by KMC
BIOMARKERS OF PAIN
Shibata M, Kawai M, Matsukura T, Heike T, Okanoya K, Myowa-Yamakoshi M.(2013). Salivary
biomarkers are not suitable for pain assessment in newborns. Early Hum Dev. 2013 Jul;89(7):503-6. doi:
10.1016/j.earlhumdev.2013.03.006. Epub 2013 Apr 10.Department of Pediatrics, Kyoto University
Hospital, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. mishibat@kuhp.kyoto-u.ac.jp
Newborns admitted to the neonatal intensive care unit are repeatedly subjected to painful or stressful
procedures; therefore, objective assessment of their pain is essential. An increasing number of scales for
neonatal pain assessment have been developed, many of which are based on physiological and behavioral
factors. Recently, salivary biomarkers have been used to assess stress in adults and older infants. This study
aimed to determine whether salivary biomarkers can be useful objective indices for assessing newborn
pain. A total of 47 healthy newborns were enrolled 3-4days after birth. Heel lancing was performed to
collect blood for a newborn screening test. Before and after heel lancing, saliva was collected to analyze
hormone levels, a video was recorded for behavioral observations, and heart rate was recorded. Two
investigators independently assessed newborn pain from the video observations using the Neonatal Infant
16
Pain Scale (NIPS). Salivary chromogranin (sCgA) and salivary amylase (sAA) levels were measured using
an enzyme-linked immunosorbent assay kit and a dry chemistry system, respectively.No definite changes in
salivary biomarkers (sCgA or sAA) were detected before and after heel lancing. However, newborn sCgA
levels were markedly higher than reported adult levels, with large inter- and intra-subject variability,
whereas newborn sAA levels were lower than adult levels. NIPS score and heart rate were dramatically
increased after heel lancing.NIPS score (behavioral assessment) and heart rate are useful stress markers in
newborns. However, neither sCgA nor sAA is suitable for assessing newborn pain.
Circumcision Pain
Bellieni CV, Alagna MG, Giuseppe B. (2013)Analgesia for infants' circumcision. Ital J Pediatr. 2013 Jun
13;39(1):38-?? Male circumcision (MC) is one of the oldest and most common operations performed all
over the world. It can be performed at different ages, using different surgical techniques, with or without
analgesia, for different religious, cultural and medical reasons.Our aim is to examine and compare the
various methods of analgesia and different surgical procedures reported in literature that are applied in
infant MC. We performed a PubMed, MEDLINE, EMBASE and Cochrane search in the papers published
since 2000: 15 studies met the inclusion criteria, most of them showing that a combined pharmacological
and non-pharmacological intervention is the best analgesic option, in particular when the dorsal penile
nerve block is combined with other treatments. The Mogen surgical procedure seems to be the less painful
surgical intervention, when compared with Gomco clamp or PlastiBell device. Only 3 papers studied
groups of at least 20 babies each with the use of validated pain scales. Data show a decrease of pain with
dorsal penile nerve block, plus acetaminophen associated to oral sucrose or topic analgesic cream.
However, no procedure has been found to eliminate pain; the gold standard procedure to make MC totally
painfree has not yet been established.
Taddio A.(2001). Pain management for neonatal circumcision. Paediatr Drugs. 2001;3(2):101-11.
Circumcision is the most common surgical procedure performed in the neonatal period in North America.
If untreated, the pain of circumcision causes both short and long term changes in infant behaviours. The
most widely studied pharmacological intervention for pain management during circumcision is dorsal
penile nerve block (DPNB) by injected lidocaine (lignocaine). Randomised controlled trials have
demonstrated its efficacy; infants premedicated with lidocaine have significantly smaller changes in
physiological and pain-related behaviours compared with infants who are not given analgesics. A metaanalysis of injection-related adverse effects (bruising/haematoma) yielded a risk of 6.7% (95% confidence
interval, 0.5 to 12.9%). Systemic toxicity from injected local anaesthesia has not been reported. Less
effective modalities include topical anaesthesia with lidocaine-prilocaine cream [Eutectic Mixture of Local
Anaesthetics (EMLA)], lidocaine cream and oral administration of sucrose. The good tolerability of
lidocaine-prilocaine cream has been demonstrated by a lack of clinically significant methaemoglobinaemia
when used appropriately. Nonpharmacological interventions (pacifier, specially designed restraint chair)
reduce distress during the procedure, and paracetamol (acetaminophen) may provide postoperative
analgesia. No single agent has been demonstrated to ameliorate pain for all infants undergoing
circumcision. A multimodal approach of pharmacotherapy is currently recommended. Studies evaluating
the efficacy of combined analgesia have demonstrated significant benefits for combinations of 2 or more
forms of treatment (such as DPNB and sucrose-dipped pacifier) compared with single interventions. The
instrument used to perform the circumcision is also important. The Mogen clamp has been shown to be
associated with a shorter procedure time and less pain compared with the Gomco clamp. If circumcision is
to be performed on infants, it is, therefore, recommended that combined analgesia and the Mogen clamp
technique are used, and nonpharmacological stress reducing interventions such as pacifiers and comfortable
restraining chairs should also be employed.
17
New heel stick procedure is in:
Folk LA. 2007. Guide to capillary heelstick blood sampling in infants. Adv Neonatal Care 7(4): 171-178.
Gives step by step guide to capillary blood sampling along with evidence-based pradtie incorporating
neonatal appropriate disinfection and non-pharmacological analgesia that contribute to improved infant
safety and comfort during the procedure.
SUCROSE
Hatfield LA. 2008. Sucrose decreases infant biobehavioral pain response to immunizations : a randomized
controlled trial. J. Nrsg. Scholarship, 40(3), 219-225. Used old Gate Controlled Theory of Pain by Melzack
& Wall, 1965. Says in article that “the plasticity of the developing brain and the long term changes that
occur in response to unmanaged pain in infants can contribute to altered perceptions of pain later in life”
(Grunau RV, Holsti L, Peters JW 2006, Long term consequences of pain in human neonates. Sem Fetal
Neonatal Med 11(4), 268-275), permanent impairment of learning,memory, behavior and increased
sensitization in childhood (Grunau RV, Whitfield MF, PetrieJH & Fryer EI 1994,Early pain experience,
child and family factors as precursors of somatization- a prospective study of extremely premature and
fullterm children. Pain 56(3) 353-359). Also says crying is considered an indicator for the presence of pain
(Ramenghi IA, Webb AV, Shevlin PM Green M Evans DJ, Levene MI. 2002, Intra-oral administration of
sweet tasting substances and infants’ crying response to immunizations: a RCT. Biol Neonate 81(3), 163169; Reis EC, Roth EK, Syphan JL, Tarbell SE, Holubkov R, 2003,Effective pain reduction for multiple
immunization injections in young infants. Arch Pediatr Adolesc Med 157(11),1115-1120), but presence of
crying does not confirm nor deny pain in infants.
SUCROSE SIDE EFFECTS: Naughton, 2013 (see MOD article for citation)
Stevens B, Craig K, Johnston C, Harrison D, Ohlsson A.(2011). Oral sucrose for procedural pain in
infants. Lancet, 377(9759), 25-26, author reply 27-28.
Stevens BJ, Yamada J, Ohlsson A. 2001. Sucrose for analgesia in newborn infants undergoing painful
procedures. Cochrane Database Systematic Reviews, #4,CD001069. “The use of repeated administrations of
sucrose in neonates needs to be investigated as does the use of sucrose in combination with other behavioural
(facilitated tucking, kangaroo care) and pharmacologic (morphine, fentanyl) interventions.”
WHY NURSES DON’T USE PAIN INTERVENTIONS
.Latimer MA, Ritchie JA, Johnston CC., (2010). Individual nurse and organizational context considerations
for better Knowledge Use in Pain CareJ Pediatr Nurs. 2010 Aug;25(4):274-81. THIS HAS A MODEL
FOR GETTING NURSES TO USE TREATMENTS BECAUSE THEY DON’T NOW (10/8/2011).
MATERNAL CARE AND PAIN PERCEPTION.
________________,2013. Review that says maternal involvement reduces pain.
de Medeiros CB, Fleming AS, Johnston CC, Walker CD (2009). Artificial rearing of rat pups reveals the
beneficial effects of mother care on neonatal inflammation and adult sensitivity to pain. Pediatr Res. 2009
Sep;66(3):272-7. Repeated pain during brain development can have long-term consequences in both
humans and animals. We previously showed that maternal care provided to pups experiencing pain reduced
adult pain sensitivity. This study tested whether sensory stimulation was responsible for this effect. Rat
pups were either mother-reared controls (MR-CON) or artificially reared (AR) with minimal (AR-MIN) or
maximal (AR-MAX) stimulation provided daily. In each rearing condition, pups were either uninjected or
injected from postnatal day (PND) 4 to 14 with saline (0.9%) or formalin (0.2-0.4%). Pain behavior and
paw inflammation were scored. Thermal sensitivity and responses to formalin were tested in adulthood
(PND 70). AR neonates, irrespective of sensory stimulation received, exhibited a pain response (p < 0.001),
even with a mild formalin dose. Maternal rearing reduced inflammation during the second week of life
compared with AR pups (p < 0.05). Early pain exposure did not modify adult pain sensitivity. However,
18
rearing altered adult pain sensitivity such that uninjected MR-CON rats had lower pain sensitivities than
uninjected AR rats (p < 0.05). This suggests that the beneficial effects of maternal rearing can be
obliterated if additional stimulation/stress occurs during the early neonatal period. In addition, this suggests
that optimal level of maternal stimulation exists that determines adult pain sensitivity.
Walker CD, Xu Z, Rochford J, Johnston CC (2008). Naturally occurring variations in maternal care
modulate the effects of repeated neonatal pain on behavioral sensitivity to thermal pain in the adult
offspring. Pain. 2008 Nov 15;140(1):167-76. Epub 2008 Sep 17 Source:Douglas Mental Health University
Institute, Department of Psychiatry, McGill University, Montreal, Canada. waldom@douglas.mcgill.ca
Abstract:Repeated pain during a critical period of development can have long-term behavioral and
physiological consequences in both human and animals. We previously showed that rat mothers caring for
pups subjected to mild pain in neonatal life increased pup licking and grooming behavior. Therefore, we
tested whether naturally occurring variations in maternal behavior would modulate the effects of repeated
mild inflammatory pain on behavioral responses to pain and stress in the adult male offspring. Rat pups
were either uninjected (UI) or injected twice daily between PND3 and PND14 with either saline (0.9%) or
formalin (0.2-0.4%) in the footpad of the hindpaw. Maternal behavior (pup licking and grooming) was
recorded under basal conditions and after reunion with the litter post injection to determine maternal
phenotype (High, Middle, Low licking). Adult offspring (PND60) were tested for their thermal sensitivity,
inflammatory pain responses after formalin injection and neuroendocrine responses to formalin injection.
Maternal phenotype significantly altered pain sensitivity after thermal stimulation, but not formalin
injection. Offspring from the High licking mothers displayed increased withdrawal latencies compared to
offspring from Low mothers, regardless of neonatal treatment. Pain responses after formalin injection were
higher in offspring receiving formalin as neonates compared to saline-treated or uninjected rats,
demonstrating a long lasting increased sensitivity to inflammatory pain. Neuroendocrine responses to
pain stress were not affected by neonatal treatment. These data suggest that changes in maternal
behavior can influence some modalities of pain sensitivity and that repeated mild inflammatory pain in
neonatal period causes hypersensitivity to formalin in the adult offspring.
Also get Veenema, AH. (2012). Toward understanding how early life social experience alters oxytocin and
vasopressin-regulated social behaviors. Homones and Behavior, 61(3), 34-312 THIS IS ALSO FOR
SEPARATION>
PAIN SCALES
Stevens B, Johnston C, Petryshen P, Taddio A (1996). Premature Infant Pain Profile: development and
initial validation. Clin J Pain. 1996 Mar;12(1):13-22.
Stevens B, Johnston C, Taddio A, Gibbins S, Yamada J. (2010)The premature infant pain profile:
evaluation 13 years after development. Clin J Pain. 2010 Nov-Dec;26(9):813-30. doi:
10.1097/AJP.0b013e3181ed1070.)
Neonatal Infant Pain Scale (NIPS). {Santos LM, Ribeiro IS, Santana RC. [Identification and treatment
of pain in the premature newborn in the intensive care unit] Rev Bras Enferm. 2012 Apr;65(2):269-75
This study aimed to analyze the parameters used by the nursing staff of a public hospital in Bahia for pain
assessment in premature newborns and to describe the interventions used to relieve the pain. This is a
qualitative descriptive study that was carried out through semi-structured interviews with ten participants,
in the period from December 2008 to January 2009. The data were analyzed through content analysis. The
results showed the use of crying and facial expression as the clinical indications of pain premature
newborns and that the interviewed participants use, on a non-systematic basis, non-pharmacological
measures in order to ease this process. We suggest the introduction of pain as the fifth vital sign to be
evaluated and the use of scales, contributing to excellence and humane care}
PAIN OUTCOMES ON DEVELOPMENT
19

Jillian Vinall, Steven P. Miller, Vann Chau, Susanne Brummelte, Anne R. Synnes, Ruth E.
Grunau (2012) Neonatal pain in relation to postnatal growth in infants born very preterm

PAIN, Volume 153, Issue 7, July 2012, Pages 1374-1381
Fabrizi, L.S. (2012) Exploring the relationship of pain and
development in the neonatal intensive care unit. Pain 153(7): 13401341.doi: 10.1016/j.pain.2012.03.013
Why are premature babies admitted to the neonatal intensive care unit (NICU)? The obvious
answer is to ensure their survival. The time that a premature infant spends in NICU is a critical
and delicate stage for the overall growth and neurodevelopment of the individual. For this reason,
the clinical procedures required to assure survival may affect the neurological development
during the relatively short hospitalization period and even later in life. Invasive medical
interventions are often required to diagnose and treat life-endangering pathophysiological
conditions. As a result, pain is an unavoidable aspect of neonatal intensive care and is an
experience that deviates most dramatically from what would occur physiologically at an
equivalent gestational age in the womb. So the question arises, what are the short and long-term
effects of early exposure to painful procedures on the developmental outcomes of premature
infants?
The effect of early exposure to pain is often studied with regards to its long-term consequences.
Pain in the NICU is associated with worse motor and cognitive development [4] and, particularly
following surgery, with persistent changes in sensory processing in ex-premature children [3],
[6] and [10]. These studies, however, have to take into account the social and environmental
factors that follow prematurity, which may themselves affect the developmental outcomes – i.e.
these factors are potential confounds [8]. It is therefore important to look at the influence of
noxious experiences on early developmental indicators and pain perception, since this analysis
may provide information as to whether successive alterations are primed while the infants are still
in the NICU. Because neurodevelopmental indices cannot be measured in neonates, the
observed indicators are bound to be indirect. Indeed, the importance of these indicators resides in
their relation to subsequent outcomes. In this complex clinical population, any study that attempts
to relate the number of painful procedures to long-term effects, is thus inherently complicated.
20
hy are premature babies admitted to the neonatal intensive care unit (NICU)? The obvious
answer is to ensure their survival. The time that a premature infant spends in NICU is a critical
and delicate stage for the overall growth and neurodevelopment of the individual. For this reason,
the clinical procedures required to assure survival may affect the neurological development
during the relatively short hospitalization period and even later in life. Invasive medical
interventions are often required to diagnose and treat life-endangering pathophysiological
conditions. As a result, pain is an unavoidable aspect of neonatal intensive care and is an
experience that deviates most dramatically from what would occur physiologically at an
equivalent gestational age in the womb. So the question arises, what are the short and long-term
effects of early exposure to painful procedures on the developmental outcomes of premature
infants?
The effect of early exposure to pain is often studied with regards to its long-term consequences.
Pain in the NICU is associated with worse motor and cognitive development [4] and, particularly
following surgery, with persistent changes in sensory processing in ex-premature children [3],
[6] and [10]. These studies, however, have to take into account the social and environmental
factors that follow prematurity, which may themselves affect the developmental outcomes – i.e.
these factors are potential confounds [8]. It is therefore important to look at the influence of
noxious experiences on early developmental indicators and pain perception, since this analysis
may provide information as to whether successive alterations are primed while the infants are still
in the NICU. Because neurodevelopmental indices cannot be measured in neonates, the
observed indicators are bound to be indirect. Indeed, the importance of these indicators resides in
their relation to subsequent outcomes. In this complex clinical population, any study that attempts
to relate the number of painful procedures to long-term effects, is thus inherently complicated.
This complexity is primarily due to the numerous confounding factors associated with prematurity,
which are difficult to control for and to separate. Often, to assess the effect of one factor, it is
normal practice to control for the others by selecting a subsample of hospitalized infants and
comparing groups whose only difference is the aspect under investigation. For example, in a trial
to investigate the effect of pre-emptive morphine analgesia, more than a third of the screened
infants were excluded from the study so that the effect of morphine analgesia was only tested on
ventilated infants [1]. In the present issue of PAIN, Vinall et al. [9] instead, made an elegant
attempt to disentangle the relation of pain experience with postnatal body weight and head
growth, – measurements commonly used in the NICU to monitor the developmental trajectory –
while including a wide cross-section of the premature population. The authors designed a
generalised linear model (GLM) to include most of the key factors known to influence body
21
growth. Using this approach they could successively assess each relationship independently, with
a particular focus on the number of painful procedures. This approach has the advantage of not
biasing the estimated correlations by cherry-picking a selected sample population, and provides a
framework to explore simultaneously the relationships between individual factors and body
growth, eventually uncovering possible interactions. It is clear that the feasibility of the model is
limited by the amount and nature of the variables taken into account and by the underlying
connections between them, but this is common to most clinical research. Unconsidered factors,
such as nutrition, fall into the unexplained variance of the data, but since the number of painful
procedure is linked to multiple medical aspects, rather than to one in particular, the correlation
with the outcome measure has been shown to be significant. Bearing in mind these
considerations, the authors found that body growth at 32 weeks gestational age is inversely
related to the number of painful procedures delivered since birth. This represents the time when
the infants received the greatest number of skin-breaking procedures. Changes later on (between
32 weeks and 40 weeks gestational age) appear to be less related to painful procedures, but
more to postnatal infection, such that when considering the overall period from birth to term-ageequivalence, body growth is not associated with painful experience. The study suggests,
therefore, that the extremely early postnatal period for the very early pre-term infants represents a
time of high susceptibility to growth retardation, and that this is related to painful experiences. It
should be pointed out that as no physiological or causal interpretation can be given to the
observed relationship, these findings are important from a strictly epidemiological point of view.
Moreover the interpretation of this study relies on the validity of the chosen indicators, body
weight and head growth, as predictors of neurodevelopmental outcome. Although these have
been found to be associated with incidence of cerebral palsy and neurodevelopmental retardation
[2], the significance of measurements such as birthweight and body growth is not evident and still
under investigation [11].
It is nevertheless interesting that the period when body growth is most directly influenced by the
number of painful procedures (from birth to 32 weeks gestational age) corresponds with a period
in which dramatic structural and functional changes are taking place in the central nervous
system [5] and [7]. For example, thalamo-cortical connections that are growing into the cortical
plate are highly plastic and possibly shaped by external inputs, such as noxious stimuli. The work
of Vinall et al. [9] provides further evidence that early exposure to noxious procedures may
adversely influence neonatal development and also demonstrates the importance of considering
short-term effects of early exposure to pain. These early changes – which can be observed when
infants are still in the NICU – may give an indication about the subsequent neurodevelopmental
trajectory of premature infants
22
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23
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Neonatal pain in relation to postnatal growth in infants born very preterm
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