The ontogeny of face recognition: eye contact and sweet taste induce face preference in 9- and 12-week-old human infants.

Nine and 12-week-old infants (N = 140) who were either calm or crying sat facing a researcher for 3.5 min. The researcher gazed into the infant's eyes with a smiling face or looked above the infant's forehead. She delivered a 12% sucrose solution via a syringe or a pacifier, or she did not deliver anything. After the exposure period, the mother held her infant over her shoulder. Infant gaze direction was recorded while the infant faced the same researcher and a stranger. The confluence of sweet taste and eye contact was necessary and sufficient for calm 9- and 12-week-olds to form a preference for the researcher. Crying infants never did so, even though eye contact and sweet taste arrested crying. Different visual-gustatory combinations induced unanticipated affective states and are discussed within the contexts of cognitive mechanisms that mediate face learning and preference, the proximate mechanisms involved, and the evolutionary significance of face recognition.

Effects of colostrum in newborn humans: dissociation between analgesic and cardiac effects.

This study evaluates the effects of colostrum, delivered via syringe or on a pacifier, on the pain and heart rate reactions of newborns undergoing routine heel-lance. This was achieved by following a quasi-randomized, controlled trial in which 60 newborn infants at Boston Medical Center, Boston, MA, were randomly assigned to receive colostrum, sucrose, or water, by syringe or on a pacifier, for a total of 6 groups (n = 10 per group). The effectiveness of an intervention was determined by comparing crying, grimacing, and heart rate differences among groups during and following blood collection. We report that colostrum, delivered by syringe or on a pacifier, did not reduce crying or grimacing relative to control infants who received water. As has been previously reported, sucrose markedly reduced both crying and grimacing, and attenuated the rise in heart rate that normally accompanies blood collection (p < .002). Water, via syringe or on a pacifier, did not prevent the increase in heart rate, nor did colostrum via syringe. In contrast, colostrum delivered on a pacifier prevented the increase in heart rate despite pain reactivity and extreme crying. The implications of this dissociation are discussed.

Skin-to-skin contact is analgesic in healthy newborns.

OBJECTIVES: To determine whether skin-to-skin contact between mothers and their newborns will reduce the pain experienced by the infant during heel lance. DESIGN: A prospective, randomized, controlled trial. SETTING: Boston Medical Center, Boston, Massachusetts. PARTICIPANTS: A total of 30 newborn infants were studied. INTERVENTIONS: Infants were assigned randomly to either being held by their mothers in whole body, skin-to-skin contact or to no intervention (swaddled in crib) during a standard heel lance procedure. OUTCOME MEASURES: The effectiveness of the intervention was determined by comparing crying, grimacing, and heart rate differences between contact and control infants during and after blood collection. RESULTS: Crying and grimacing were reduced by 82% and 65%, respectively, from control infant levels during the heel lance procedure. Heart rate also was reduced substantially by contact. CONCLUSION: Skin-to-skin contact is a remarkably potent intervention against the pain experienced during heel stick in newborns.

Milk-induced hypoalgesia in human newborns.

OBJECTIVE: To determine whether milk and its components reduce crying in newborns during and after blood collection for phenylketonuria evaluation. METHODOLOGY: Seventy-two normal newborns ingested 2 mL of milk (Similac), Ross Special Formula, fat, protein, lactose, sucrose, or water for the 2 minutes preceding blood collection via heel lance. Crying duration during and for the 3 minutes after the procedure was determined by scorers who were blind to the ingestive substance. RESULTS: Sucrose and Similac each reduced crying during the blood collection procedure. Sucrose, fat, protein, and Ross Special Formula were effective during the 3-minute recovery period. Neither water nor lactose were effective during or after blood collection. CONCLUSION: Milk and some of its components are antinociceptive in human newborns. Based on previous studies, reduced crying during and after painful stimulation may be mediated through endogenous opioids. These findings are of potential clinical significance: natural protective mechanisms, normally engaged during suckling, may safely and noninvasively be activated to reduce newborn crying to painful stimulation.

Infant formula quiets crying human newborns.

Milk (Similac), sucrose (12% wt/vol), or water were delivered to crying normal newborns once per minute for 5 minutes, in a volume of 0.1 mL/delivery. Milk and sucrose markedly reduced infant crying, and this calm persisted during the 3 minutes after substance delivery. Infants who received water were only marginally quieted, and this calm did not persist. Despite quieting agitated infants, milk did not cause them to bring their hands to their mouths during the period of milk treatment, whereas infants who received sucrose did bring their hands to their mouths. These data demonstrate that milk effectively quiets human newborns, that its quieting effects endure, and that the mechanisms that quiet and that underlie hand-in-mouth engagement are separable and independent.

Reduced heat loss following sucrose ingestion in premature and normal human newborns.

To determine the energy savings caused by sucrose taste, we measured heat loss through direct calorimetry for 23 premature and normal term infants who were studied a total of 31 times. Following stabilization in the calorimeter, crying was induced by applying 1 ml cold water to the infant's foot. After 4 min, 0.1 or 0.2 ml sucrose were delivered intraorally through a remote syringe to arrest crying. Crying was accompanied by a 13.2% increase in metabolic rate that was quickly and completely reversed during crying cessation caused by sucrose taste. Heat loss was inversely and linearly related to infant body weight. The implications of these findings for minimizing crying and energy expenditure in normal newborns and especially in ill or small newborns are discussed.

Suckling and sucrose ingestion suppress persistent hyperalgesia and spinal Fos expression after forepaw inflammation in infant rats.

Sweet taste and nonnutritive suckling produce analgesia to transient noxious stimuli in infant rats and humans. The present study evaluated the pain-modulating effects of sucrose and suckling in a rat model of persistent pain and hyperalgesia that mimics the response to tissue injury in humans. Fore- and hindpaw withdrawal latencies from a 30 degrees or 48 degrees C brass stylus were determined in 10-day-old rats following paw inflammation induced by complete Freund's adjuvant (CFA; 1:1 injected s.c. in a 0.01 ml volume). CFA markedly decreased escape latencies to both 48 degrees and 30 degrees C stimulation, thereby demonstrating thermal hyperalgesia and mechanical allodynia. The combination of nonnutritive suckling and sucrose (7.5%, 0.01-0.06 ml/min) infusion markedly increased escape latencies to forepaw stimulation in both CFA-treated and control rats. In contrast, intraoral sucrose and suckling did not increase hindpaw withdrawal latencies in either control or CFA-inflamed rats. The effect was specific to sweet taste because neither water nor isotonic saline infusion affected forepaw escape latencies. Parallel findings were obtained for CFA-induced Fos-like immunoreactivity (Fos-LI), a marker of neuronal activation. Fos-LI was selectively induced in cervical and lumbar regions ipsilateral to forepaw and hindpaw inflammation, respectively. Suckling-sucrose treatment significantly reduced Fos-LI at the cervical but not at the lumbar regions. These findings demonstrate: (i) the development of persistent pain and hyperalgesia in 10-day-old rats that can be attenuated by endogenous pain-modulating systems activated by taste and nonnutritive suckling; (ii) the mediation of the sucrose-suckling analgesia and antihyperalgesia at the spinal level; and (iii) a differential rostrocaudal maturation of descending pain-modulating systems to the spinal cord of 10-day-old rats. These findings may provide new clinical approaches for engaging endogenous analgesic mechanisms in infants following tissue injury and inflammation.

Interactions between contact and chemosensory mechanisms in pain modulation in 10-day-old rats.

Antinociception was evaluated in 10-day-old rats while suckling or in contact with the mother. Testing occurred during, immediately after, or at 30 and 60 s following milk-induced hyperextension. Hyperextension-induced hypoalgesia terminated immediately with stretch cessation. For suckling rats, baseline escape levels were reacheived within 1 min. For contact rats, baseline levels were also manifest at 30 s but were elevated by 1 min. Sublingual infusions into the anterior portion of the mouth in rats that were either suckling or in contact caused a 20-25-s increase in escape latencies. For suckling rats, escape latencies returned to baseline levels immediately at infusion termination. For contact rats, latencies continued to be elevated for at least 5 min postinfusion. Thus, 3 classes of mother-infant interactions, contact, suckling, and hyperextension during milk letdown, cause varying degrees of hypoalgesia in 10-day-old rats.

Mothers and their infants: peptide-mediated physiological, behavioral and affective changes during suckling.

Milk delivery through suckling lowers human newborn heart and metabolic rats. In rat and human infants pain threshold is markedly elevated and crying is arrested. These changes are induced by milk flavor or sugar taste which release central endorphins. In rats the changes are naloxone reversible; human infants born to women who were maintained on methadone during pregnancy were not quieted by sweet taste. Cholecystokinin (CCK) released during milk absorption quiets infant rats as does beta-casomorphine derived from casein hydrolysis. Through opioid and CCK mediation, milk also causes affective change that facilitates infant-mother bonding.

beta-Casomorphin causes hypoalgesia in 10-day-old rats: evidence for central mediation.

Two experiments determined behavioral effectiveness of beta-casomorphins (beta-CM) in 10-d-old rats by evaluating changes in heat escape latency from a 48 degrees C stimulus applied to a forepaw. In one study rats were injected systemically with beta-CM4, -5, or -7 at a dose range of 0.1-2.5 mg/kg. Only beta-CM5 was effective, and the dose-response relationship was graded. The second study evaluated the locus of action of beta-CM5 through two experimental manipulations: first, by injecting it (0.25 microgram) into the lateral ventricles and by attempting to block its effects with systemic injections of naloxone. Second, rats received intracerebroventricular injections of naloxone (0.25 microgram) and systemic injections of beta-CM. beta-CM was effective centrally, suggesting central detection of the drug. Naloxone injected into the lateral ventricles blocked the effects of systemic administration of beta-CM, implying that circulating beta-CM or their precursors cause behavioral change through central mechanisms.

Mother as shield: differential effects of contact and nursing on pain responsivity in infant rats--evidence for nonopioid mediation.

To determine how rat mothers protect their pups against pain, we applied focal heat (34-51 degrees C) to the ear or shoulder of 10-day-old rats that were isolated, in contact among themselves or with their mother, suckling nonnutritively, or in the hyperextension position normally caused by milk letdown. Relative to isolated rats, contact doubled withdrawal latencies from heat (43 or 45 degrees C) applied to the ear. Suckling quadrupled heat-escape latencies. During hyperextension, rats essentially did not escape from thermal stimulation of up to 48 degrees C. Protection provided by maternal contact, especially suckling, was not mediated by either mu or kappa opioid receptors: neither systemic injections of naltrexone nor norbinaltorphimine reduced heat-escape latencies. Morphine (0.125 and 0.250 mg/kg) added to the effects of contact but multiplied the effects of suckling to produce heat-escape latencies that were upward of 2 min.

Pain-reducing properties of sucrose in human newborns.

To assess the characteristics of sucrose as a pain-reducing substance, crying in 72 newborn humans during and after blood collection via heel prick was determined. In the first study infants drank 2 ml of water or 2 ml of a 0.17-0.34- or 0.51-M sucrose solution 1 min prior to blood collection. In the second experiment, a delay of 30, 60, 90, 120 or 240 s was imposed between sucrose intake and the initiation of blood collection. The dose-response function for concentration was flat. The most effective time delay was 120 s. The effectiveness of the 2-min interval accords with previous findings of endogenous opioid release caused by sucrose taste. The flat dose-response function extends findings in rats and humans that the calming and pain-reducing effects of sucrose are not influenced by either concentration or volume, suggesting that the transduction from gustatory afferent to opioid-mediated efferent is of an on-off nature and not graded.

Behavioral and physiological consequences of suckling in rat and human newborns.

Suckling, in addition to yielding milk, water and calories, exerts profound behavioral effects on newborn rats and humans. In particular, suckling induces feelings of calm, reduces heart rate and metabolic rate, causes infants to bring their hands to their mouths and elevates the pain threshold. These changes are mediated by opioid and non-opioid systems, each having its own separate behavioral and neurological characteristics. The implications of suckling-induced changes for long-term motivational and cognitive change are discussed.

Some comparisons among the calming and pain-relieving effects of sucrose, glucose, fructose and lactose in infant rats.

Ultrasonic vocalizations were recorded from 10-day-old albino rats while they were isolated from their dam and siblings. Each rat received a 1.0% BW intra-oral infusion of sucrose, fructose, glucose or lactose at a concentration range of 0.22-0.66 M for 3 min and their vocalizations were determined during the infusion and for an additional 7 min. Sucrose, fructose and glucose all significantly reduced vocalizations to about 50% of baseline levels, whereas lactose, the milk sugar, was ineffective. Moreover, the dose-response function was flat for the three effective sugars. In a second experiment, the effects of these sugars on heat escape latency were measured. Sucrose, fructose and glucose each elevated the latency with which infant rats removed a paw from a 48 degrees C surface; lactose did not. These findings of lactose ineffectiveness and the flat dose-response function for the other three sugars exactly parallel those obtained for human newborns. Their implications are discussed.

A new look at some old mechanisms in human newborns: taste and tactile determinants of state, affect, and action.

Three studies of normal human newborns and of newborns of methadone-maintained mothers evaluated how orotactile (pacifier) and orogustatory (sucrose) stimulation, alone and in combination, affected crying behavior, heart rate, gross motor activity, eye opening, and hand-mouth coordination. For each measure of infant state, pacifier and sucrose stimulation each caused significant changes that followed very different time courses. Orotactile (pacifier) stimulation precipitated immediate changes in all behaviors, and, when the pacifier was removed, all behaviors soon reverted to baseline levels. The changes precipitated by orogustatory (sucrose) stimulation were more gradual but extended well beyond the end of sucrose administration. Although both pacifier and sucrose influences are mediated orally as opposed to in the stomach or intestine, the effects involve different brain pathways. The fact that infants born to methadone-maintained mothers did not change their behaviors during or after sucrose administration but that their reactions to pacifier stimulation could not be distinguished from those of normal infants suggests that reactions to sucrose are mediated centrally by endogenous opioids while those to the pacifier work through other central mechanisms. These findings with human newborns are consonant with those of many animal studies that have also shown rapid onset and rapid offset for contact- and suckling-induced behavioral changes, slower onset and slower offset for changes induced by taste, and opioid mediation of changes induced by the taste of sucrose. Orogustatory and orotactile influences on affect, action, and cardiovascular function are discussed from the perspectives of energetics and growth, central determinants of state, motivation, and learning during the newborn period.

Endogenous cholecystokinin reduces vocalization in isolated 10-day-old rats.

Devazepide, the cholecystokinin (CCK) A receptor blocker, markedly and specifically affected the behavior of 10-day-old rats isolated from their mother and siblings. Whereas intraoral infusions of milk or fat, which cause CCK release, calmed infants, that is, reduced levels of ultrasonic vocalization, devazepide fully blocked this reduction. Devazepide did not affect calming caused by sucrose infusions, which do not release CCK. Moreover, devazepide did not reduce the elevated pain limen caused by milk or fat infusions. These data parallel earlier findings obtained with administration of exogenous CCK and implicate endogenous CCK in the maintenance of infant steady state and calm. The possibility that CCK contributes to the normal development of mother-infant affectional systems is discussed.

The development of morphine-induced antinociception in neonatal rats: a comparison of forepaw, hindpaw, and tail retraction from a thermal stimulus.

Two parallel experiments in rats 2-21 days of age investigated the onset and characteristics of morphine-induced antinociception. One measure of reactivity to pain, limb retraction from a hotplate, was utilized for three different limbs (forepaw, hindpaw, and tail) to chart the development of opioid sensitivity. Morphine-induced antinociception, even in 2-day-old rats, was obtained for all limbs, in a dose-related fashion, and reached peak sensitivity at 6-7 days of age. Naltrexone did not affect limb retraction latencies in nonmorphine treated rats at any age. These studies demonstrate early antinociception to low doses of an opiate and establish that the pain system, like positive reinforcement systems, is opiate sensitive.