Pain, 20 (1984) 77-86

Elsevier 77

PAI 00669

Pain in Infancy: Neonatal Reaction to a Heel Lance

Mark E. Owens *J and Ellen H. Todt **

* Department of Psychiatry, University of Utah Medical Center, 50 North Medical Drive, Salt Lake City,

UT 84132, and ** Psychology Seruice, Veterans Administration Medical Center, 500 Foothill Boulevard, Salt Lake City, UT 84148 (U.S.A.)

(Received 24 October 1983, accepted 12 March 1984)

Summary

A combined single subject and group design was used to investigate changes in heart rate and crying in response to a heel lance, non-invasive tactile stimulation and baseline periods in 10 male and 10 female infants, each in their second full day of life. Heart rate was measured with an electrocardiogram. Percentage of time crying was computed from observations of audiotapes. Results for individual subjects indicated that heart rate and percentage of crying were consistently increased by the heel lance but that there was often wide baseline variability in the two measures. Analysis of variance indicated that responses to heel lance were higher than responses to tactile stimulation which were in turn higher than responses to baseline for both heart rate and percentage of crying (P < 0.01). No significant sex dif- ferences were found. It was suggested that the increases in heart rate and crying in the context of a tissue damaging stimulus indicated that the infants experienced pain and that pain in infants can be reliably measured in clinical settings.

Introduction

There has been no systematic research on neonatal response to potentially noxious medical procedures: Most existing reports are anecdotal and conflicting. For example, Merskey [21] asserted that circumcision at the age of 3-4 days leads to little or no objection from the infant. In contrast, Poznanski [27] stated that circumcisions result in a total body movement with screams and cries. Neither author presented data to support the statements.

’ All proofs and correspondence should be sent to the first author.

0304-3959/84/$03.00 0 1984 Elsevier Science Publishers B.V.

It is common practice for health care providers to use little or no anesthetic with infants for procedures such as endotracheal intubation [8]. The penile nerve block for circumcision is seldom used although the technique has been available for years [17] and has been shown to attenuate heart rate increases during circumcision of

2-day-old infants [31]. When physicians prescribe postoperative analgesics for children, they typically prescribe less than the recommended dosage and nurses typically administer only about half of what is prescribed [20].

The practice of reduced attention to possible discomfort of infants during potentially noxious procedures appears to rest on the assumption that there is no infant response to such procedures or that any existing response does not indicate

subjective distress on the part of the infant. The present study was designed to address the first assumption. Specifically, it was designed to measure differential infant reaction to a heel lance, to non-invasive tactile stimulation and to periods of no scheduled stimulation (baseline).

Two response systems were included in this study: heart rate and crying. There were several a priori reasons for picking these two systems. Crying has face validity as a measure of pain in infancy. It has been suggested that crying is the best dependent variable for study of pain in prelingual children [18]. Crying has been studied for its value in eliciting attention from caregivers [22,25]. Such an alerting

device has obvious evolutionary value in the context of tissue damage [9,15]. In the present study, a very simple measure of crying was obtained. The presence

or absence of crying was noted during successive 3 set intervals. Amount of time spent crying is thus measured. Normal methods for measuring duration are inappli-

cable to crying because of its sporadic nature caused in part by the natural absence of sound during inspiration.

Heart rate was also included as a dependent variable. Heart rate has the advantage of being relatively easy to obtain with a variety of methods. It has been well studied in infants [5,24]. Changes in infant heart rate have been shown to be bidirectional. Heart rate reliably increases in response to some classes of stimuli and decreases to others. Heart rate generally decreases briefly when the infant is presented with an auditory or visual stimulus of mild intensity, to stimuli discrepant from an infant’s prior experience and to offset and onset of stimuli [3-51. Heart rate increases have been shown to occur in 6-9-month-old infants as an expression of fear or distress as a result of exposure to strangers or heights [6,29]. The stress of labor and delivery causes fetal heart rate to increase [14,19]. A study on circumcision found large increases in heart rate for infants who did not receive local anesthesia before the procedure [31] and adults typically respond to acute pain with increased

heart rate [7,23,30]. Two secondary questions addressed by the study are whether or not there are

differences in responding due to gender and whether conditioning can occur with an aversive stimulus such as the heel lance. Adults show sex differences in response to pain. For example, men have been shown to tolerate pressure-induced pain longer than women [32]. Apley [2] found that recurrent abdominal pain is more prevalent in girls than in boys from the age of 8 onward. It is unknown whether sex differences in pain perception and expression exist in infancy. Reactions to the heel lance were

examined for possible sex differences with the limitation of a relatively small sample. If conditioning can occur with an aversive stimulus such as the heel lance (i.e., if

other stimuli can take on functional characteristics of the heel lance), then there are implications for developmental processes in pain. The heel lance procedure was essentially a combination of the tactile stimulation phase (rubbing the heel with an alcohol pad) and the actual lancing procedure. The tactile stimulation could be

considered a potential conditioned stimulus and the heel lance an unconditioned aversive stimulus_ If tactile stimulation which follows a pairing of tactile stimulation and heel lance is reacted to more strongly, then there is limited evidence for conditioning.

Method

Subjects Subjects were 10 male and 10 female infants on the well baby unit of a university

medical center. Subjects’ ages ranged from 30 to 54 h (in the second full day of life). All babies included weighed 6-8.5 lb (2720-3855 g), had APGAR scores of at least 7 at 1 and 5 min of age [l], had estimated gestation of at least 37 weeks and had been fed no more than 3 h before the experiment began. Informed consent was obtained from mothers prior to the experimental day. Mothers of infants were relatively young (median age = 21 years). All mothers were Caucasian. For two-thirds

of the women, family income was under $lO,~O per year. Nearly half of the women were single, separated or divorced. Only 12 of the 20 women had completed a high school education.

Apparatus A Tektronix Model 414 three-lead ECG unit was used to measure heart rate.

Electrodes were placed on the manubrium, over the left tenth rib in the midclavicu- lar line and the ground electrode was placed over the right tenth rib. A Tektronix Model 400 strip recorder continuously recorded cardiac activity. A Panasonic Model RQ-331 cassette recorder was used to record infant cries. A Realistic 200 Sz dynamic microphone was placed 20-30 cm from the infant’s mouth.

Procedure Measurements were conducted in a separate room in the nursery. Only the infant

under observation, two experimenters and the lab technician were present. The lab technician was present only during the heel lance procedure. All measurements were conducted between 6 and 7 a.m. Infants were dressed in pajama tops and diapers and were loosely covered with a blanket. They were in a crib measuring 40 cm x 75

cm. A warm water compress was placed on both of the infant’s feet 15-30 min prior to data collection in order to increase vascular flow and hence make the blood sample easier to obtain. ECG and audio recordings were made continuously throughout the experiment. For ease of presentation, treatment phases are abbreviat- ed as A for baseline, B for tactile stimulation and C for heel lance.

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During A phases there was no scheduled stimulation. The phase was of variable duration depending on its place in the sequence. Initial A phases lasted 5 min. When an A phase followed a B phase, it lasted 3 min and when it followed a C phase it lasted 7 min. Occasionally A phases which preceded C phases were slightly longer due to practical difficulties in having the lab technician present at precisely the right time.

During B phase the blanket was partially removed from the infant. The warm water compress was removed from the heel opposite the heel lanced in phase C. The heel was grasped and the plantar aspect of the heel was stroked with a Webcol alcohol pad for 1.5 min.

The C phase began with partial removal of the blanket. The warm water compress was removed and the heel cleaned with a Webcol alcohol pad. A Monoject lancet was inserted 2.0 mm into the medial or lateral aspect of the plantar surface of the heel. The area was massaged until an adequate blood sample was obtained. The blood sample consisted of saturating 3 circles each 1 cm in diameter on a heavy piece of paper. Repeated sticks of the heel were occasionally necessary to obtain the sample. Following the sample a cotton ball was pressed to the lance site and held briefly. The blanket was replaced and the phase ended.

The order of presentation of phases that a subject received took one of two forms, ABACA or ACABA. Order was determined randomly for each subject except that subjects were forced into cells to complete the design. Five males and 5 females received each order of presentation.

Results

Heart rate was calculated for each 15 set interval or portion of 15 set Interval throughout all phases. If less than 5 set remained in the final portion of a phase, the data were dropped. Heart rate was computed by counting beats on the strip chart and was expressed in beats per minute (bpm). If less than 5 set of the 15 set interval proved to be legible, no heart rate was computed for that interval. This occurred in less than 1% of the intervals.

Audiotapes of infant cries were rated for presence or absence of crying within 3 set intervals. Crying was defined as ‘audible distress vocalization.’ Interobserver reliability was computed for all subjects and all phases. Overall percentage agree- ment for phases ranged from 83 to 100% and averaged 96.2%. A more conservative estimate of reliability is provided by a weighted average percentage agreement for occurrences and non-occurrences [12,13]. This value was computed for each phase for each of 4 randomly selected subjects. The values ranged from 19 to 100%. The median value was 83%. Three different observers participated in the rating of the audiotapes. Observer 1 rated all the tapes while observers 2 and 3 split duties. The mean ,percentage agreement for observer 1 and observer 2 was 96.0% and for observers 1 and 3, 97.2%. Tapes for two infants were randomly selected. The phases were randomly ordered and then rated. Observers were then blind to whether the phase being rated was A, B or C. The mean percentage agreement for phases rated

blind by observers 1 and 2 was 95.9%. Results from observer 1 were used to compute

all crying statistics. Fig. 1 shows results from individual subjects. One subject was chosen at random

from each of the 4 groups. (Each group represented a combination of male/female and B first/C first order.) Crying and heart rate were plotted on the same abscissa. Crying was plotted as percentage of 3 set intervals within 15 set intervals during which crying occurred.

The figure shows occasional wide variability during initial baselines for heart rate and crying. For subjects 5, 9 and 18 the C phases have a discriminable difference in crying rate from the preceding A phases. For subject 12, however, crying had such a

high baseline rate as to make it impossible to see a clear effect of the heel lance. Heart rate generally showed an increase following the lance although again for subject 12 the baseline heart rate was variable and relatively high so that there was no clear difference between the C phase and preceding A phase. The reactions to tactile stimulation were much less predictable than reactions to heel lance.

All of the infants in Fig. 1 had a 100% crying rate soon after the heel lance. Of the

sample of 20 infants, all except one showed zero latency from the heel lance to 5 consecutive 3 set intervals of crying. Latency was computed by counting the number

S9 - MALE

$12 -FEMALE

Fig. 1. Heart rate and percentage of crying for each 15 set interval for individual subjects 5, 9, 12 and 18.

The arrow in the C phase indicates the interval in which the heel lance occurred. For ease of preparation,

symbols for data points were eliminated if behavior rates were stable. This often occurred for percentage

of crying.

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of 3 set intervals between the interval which contained the heel lance and the first of 5 consecutive intervals in which crying occurred. For comparison, one 3 set interval was randomly selected for each subject and latency from that interval to 5 consecu- tive 3 set intervals of crying or to the end of the final phase was calculated. The latency ranged from 0 to 320 intervals and averaged 46.4 intervals. Duration of crying following heel lance was computed by counting the time from the lance to the beginning of a 15 set interval that was cry free. This duration averaged 207 set (S.D. = 118 set).

The direction of change of heart rate from the 15 set interval before the interval with the lance compared to the 15 set interval following was very consistent. In 19 of 20 subjects, heart rate increased from the interval preceding the lance to the interval following. The one subject which was an exception had equal heart rates in the intervals compared.

Heart rate did not reach its ceiling as quickly as did the measure of crying. The mean latency from the heel lance to the beginning of the 15 set interval in C phase with the highest heart rate was 78.0 set (SD. = 38.9 set). Heart rate sometimes did not peak until after the C phase had ended as in subjects 5 and 9. The mean of the highest heart rate in a 15 set interval during C phases was 179.4 bpm (S.D. = 13.4 bpm), a mean increase of 49.0 bpm (S.D. = 17.5 bpm) over the mean heart rate of the preceding A phase. Duration of increased heart rate was defined as the amount of time between the heel lance and when the heart rate returned to within 10 bpm of the mean heart rate of the preceding A phase. Mean duration was 217.6 set (S.D. = 105.9 set).

It is apparent that heart rate and crying tend to covary. Correlation coefficients were calculated for the subjects illustrated in Fig. 1. The correlations were, respec- tively, 0.48, 0.74, 0.89 and 0.84. All were statistically significant via t tests at P < 0.01. Results of t tests in order were: t (81) = 4.87, t (95) = 10.79, t (72) = 16.71 and t (77) = 13.50.

Analyses of variance on all 20 subjects were performed in an effort to determine whether there were sex differences, differences due to treatment order (B first vs. C first) and to examine differences between phases. Separate analyses were conducted for the two dependent variables. They were 2 (sex) x 2 (order) X 5 (phases) analyses of variance with repeated measures on phases. Data entered in the analyses were individual subject means for each phase. Results of the analyses were very similar for the two dependent variables. The F values for treatment phases were statistically significant for heart rate and crying. The values were, respectively: F (4, 64) = 31.7, P < 0.01; F (4, 64) = 30.56, P -c 0.01. Both F values remain significant with con- servative Geisser-Greenhouse degrees of freedom at P -C 0.01. See Fig. 2 for means

and standard deviations for each phase. An examination of individual means of the various treatment phases was carried

out via Newman-Keuls procedures. The results for heart rate and crying were identical. The C phases were different from all the other phases and the B phases were different from the A phases. The A phases did not differ from one another. All differences were significant at P -C 0.01. Fig. 2 shows means for each treatment phase for heart rate and crying averaged over all subjects. Heart rate and crying were

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0 PERCENT CRYING

q HEART RATE

N=20

A, A, A, B C

Fig. 2. Mean heart rate and mean percentage of crying averaged over all subjects. The vertical lines over the bars indicate 1 S.D.

elevated by tactile stimulation and were further elevated in response to the heel lance procedure.

The F value for order of presentation for crying achieved statistical significance, F (1, 16) = 6.08, P < 0.05. Comparison of the B phases which preceded or followed C phases via t test did not approach statistical significance, t (18) = 0.93, P > 0.30. These results do not support the hypothesis that B phases would be responded to more strongly because of previous exposure to the C phase; that is, there is no support for the occurrence of conditioning effects. Rather, examination of the means showed that the largest contribution of variance to the order effect came from the group of female infants who received B first. Their crying scores were elevated across all phases, including the A phases, suggesting they were ‘fussy’ babies across all phases. Thus, the significant F value for order appears to derive from sampling error due to scores of the ‘fussy’ babies.

The results refute statements that there is little or no reaction of newborns to tissue damaging medical procedures. Two-day-old infants react consistently to a heel lance with crying and increased heart rate. It is possible to measure these changes reliably in a clinical setting with measurement systems available in the setting, that is, ECG monitors and the human ear. There was often baseline variability in crying and heart rate which made it more difficult to discriminate the reactions on an individual basis.

The response to heel lance in the current study was discriminable from the reaction to tactile stimulation. The response to tactile stimulation was in turn

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different from that in baseline periods. It may be that the tactile stimulation was mildly aversive to infants, perhaps because of the restraint of the foot and cooling produced by the evaporation of alcohol.

The heart rate elevations produced by heel lance were very similar to those

reported in response to circumcision. Williamson and Williamson [31] found a 54.1 bpm rise to an average of 181.0 bpm for unanesthetized infants undergoing circumcision. This compares to a 49.0 bpm rise to an average of 179.0 bpm in

response to heel lance. It took an average of approximately 3.5 min for heart rate to return to baseline after either procedure. These heart rate changes are markedly

different from those reported to occur in response to auditory or visual stimuli which are decelerations of 6-10 bpm over a 4-8 set interval [3,16].

Crying consistently began shortly after the lance. It makes sense that crying

would begin very quickly if it is to communicate to caregivers the potential of continuing tissue damage. Crying out in pain is characteristic of many species and especially of mammals [9,18]. The brief-interval observation method of measuring

crying proved to be reliable with a very simple definition of crying, that is, an ‘audible distress vocalization.’ One drawback of the measure was its relative lack of sensitivity. The measure reached its ceiling value often. Additional sensitivity might well be provided by a measure of loudness. It would be relatively easy to measure loudness with special equipment in a controlled experimental situation. It would be more difficult to obtain reliable measurements in the normal clinical setting of a hospital nursery because of ambient noise levels. The purpose of the present experiment was to measure pain responses in a situation very similar to normal clinical situations and with methods readily available.

The response to B which followed C was not different than the response to B which preceded C. Thus there was no evidence of sensitization, fatigue or condition- ing. Operant and Pavlovian conditioning have been implicated as important processes

in pathological pain states [lo]. Evidence for such processes in infants would be important for several reasons. First, it is sometimes argued that a pain response in

infants is unimportant because infants do not ‘remember’ the experience [12]. Evidence for alterations in later responding would refute such an argument. Dis- covery of learning influences on pain at such an early age would have impact on the still common view that pain is a fixed reaction pattern, governed only by the amount

of nociceptive stimulation. Some authors [e.g., 211 have argued that neonates do not experience subjective

distress because of their relatively primitive stage of neurological development. It could be argued that the responses in this study represent reflex responses to noxious stimulation and are not coincident with subjective distress. The presence of subjec- tive distress is relevant to most current concepts of pain, for example, Sanders’ [28] trimodal behavioral conceptualization of pain. Space does not allow an adequate treatment of the conceptual issues involved in infant pain and they are best treated at some length [26]. Briefly, however, there are some heuristic advantages to using the term pain to label the increase in heart rate and crying in the context of tissue damage. Using pain seems to offer little cause for confusion. Current discussion in the literature uses awkward terms such as ‘physiologic pain-stress response’ [31], or

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avoids the use of pain entirely. Pain offers a ready identification for a set of experimental questions. It suggests the assumption of subjective distress and places the burden of proof on those who assume a lack of distress. It is, therefore, likely to motivate more research for humanitarian reasons.

There exist numerous opportunities for research on pain in infants and develop- ing children. An ontogenetic understanding of pain responses would be most helpful to clinicians and theoreticians. There are many necessary noxious medical proce- dures that are performed on infants and children. Lon~tudinal research would be relatively easy to accomplish. Study of additional response systems such as facial expression and psychoendocrine reactions would likely be informative.

Acknowledgements

We are indebted to Tish Arch&eta and Gustav0 Loza for assistance in data collection. Drs. George Endo and Howard Sloane gave helpful advice in the design stages. The kind cooperation of the nursing staff of the Well Baby Unit of the University Hospital is gratefully acknowledged.

References

1 Apgar, V.A., A proposal for a new method of evaluation of the newborn infant, Anesth. Analg. Curr. Res., 32 (1953) ZO-267.

2 Apley, J., The Child with Abdominal Pains, 2nd edn., Blackwell, London, 1975.

3 Berg, KM., Berg, W.K. and Graham, F.K., Infant heart rate response as a function of stimulus and

state, Psychophysiology, 8 (1971) 30-44.

4 Brown, J.W., Leavitt, L.A. and Graham, F.K., Response to auditory stimuli in 6- and 9-week-old

infants, Develop. Psychobiol., 10 (1977) 255-266.

5 Campos, J.J., Heart rate: a sensitive tool for the study of emotional development in the infant. In:

L.D. Lipsitt (Ed.), Developmental Psychobiology, Lawrence Erlbaum, Hillsdale, NJ, 1976, pp. 1-31.

6 Campos, J.J., Emde, J., Gaensbauer, T. and Henderson, C., Cardiac and behavioral inter-relationships

in the reactions of infants to strangers, Develop. Psychol.. 11 (1975) 589-601.

7 Cannon, W.B., Bodily Changes in Pain, Hunger, Fear and Rage, 2nd edn., Appleton, New York, 1929.

8 Craig, K.D., Ontogenetic and cultural influences on the experience of pain in man. In: H.W.

Kosterlitz and L.Y. Terenius (Eds.), Pain and Society, Verlag Chemie, Weinheim, 1980, pp. 37-52.

9 Darwin, C., The Expression of the Emotions in Man and Animals, John Murray, London, 1872.

10 Fordyce, W.E., Behavioral Methods for Chronic Pain and Illness, Mosby, St. Louis, MO, 1976.

11 Gross, S.C. and Gardner, G.G., Child pain: treatment approaches. In: W.L. Smith, H. Mershey and

SC. Gross (Eds.), Pain: Meaning and Management, Spectrum, New York, 1979, pp. 127-142.

12 Harris, F.C. and Lahey, B.B., A method for combining occurrence and nonoccurrence interobserver

agreement scores, J. appl. Behav. Anal., 11 (1978) 523-527.

13 Hartmann, D.P., Considerations in the choice of interobserver reliability estimates, J. appl. Behav.

Anal., 10 (1977) 103-116.

14 Hon, E.H., Observations on ‘pathologic’ fetal bradycardia, Amer. J. Obstet. Gynec., 77 (1959)

1084-1098.

15 Izard, C.E. and Dougherty, L.M., Two complementary systems for measuring facial expressions in infants and children. In: C.E. Hard (Ed.), Measuring Emotions in Infants and Children, Cambridge University Press, Cambridge, 1982, pp. 97-126.

86

16 Kagan, J., Kearsley, R.B. and Zelazo, P.R., Infancy: its Place m Human Development, Harvard

University Press, Cambridge, MA, 1978.

17 Kirya, C. and Werthmann, M.W., Neonatal circumcision and penile dorsal nerve block: a painless

procedure. .I. Pediat., 96 (1978) 998-7000.

18 Levine, J.D. and Gordon, N.C., Pain in prelingual children and its evaluation by pain-induced

vocalization, Pain, 14 (1982) 85-93.

19 Lipton, E.L., Steinschneider, A. and Richmond, J.B., Autonomic function in the neonate. VII.

Maturational changes in cardiac control. Child Develop., 37 (1966) l-16.

20 Manning. D.F., Analgesic Management of Postoperative Pain in Children: a Retrosprctlve Study,

Master’s Thesis, University of Utah, Salt Lake City, UT. 1979.

21 Merskey. H., On the development of pain, Headache, 10 (1970) 116-123.

22 Murray, A.D.. Infant crying as an elicitor of parental behavior: an examination of two models.

Psychol. Bull.. 86 (1979) 191-215.

23 Obrist. P.A., Cardiovascular differentiation of sensory stimuli, Psychosom. Med., LS (1963) 450-459.

24 Obrist, P.A., Light, K.C. and Hastrup, J.L.. Emotion and the cardiovascular system: a critical

perspective. In: C.E. Izard (Ed.), Measuring Emotions in Infants and Children. Cambridge University

Press, Cambridge, 1982. pp. 299-316.

25 Ostwald, P., The sounds of infancy, Develop. Med. Child Neural.. 14 (1972) 350-361.

26 Owens, M.E., Pain in infancy: conceptual and methodological issues. Pain, 20 (1984) in press.

27 Poznanski, E.O., Children’s reactions to pain: a psychiatrist’s perspective. Clin. Pediat.. 15 (1976)

1114-1119.

28 Sanders, S.H.. A trimodal behavioral conceptualization of clinical pain, Percept. Motor Skills. 48

(1979) 551-555.

29 Schwartz, A., Campos. J.J. and Baisel. E.. The visual cliff: cardiac and behavioral correlates on the

deep and shallow sides at five and nine months of age, J. exp. Child Psychol.. 1.5 (1973) X6-99.

30 Sternbach, R.W., Pain: a Psychophysiological Analysis, Academic Press. New York, 1968.

31 Williamson, P.S. and Williamson. R.N., Physiologic stress reduction by a local anesthetic during

newborn circumcision, Pediatrics, 71 (1983) 36-40.

32 Woodrow, K.M., Friedman, G.D., Siegelaub. A.B. and Collen, M.F.. Pain tolerance: dtfferencea

according to age, sex and race, Psychosom. Med., 34 (1972) 548-556.