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Mencía, S.;  Alonso, C.;  Pallás-Alonso, C.;  López-Herce, J. Pain in Fetuses, Neonates and Children. Encyclopedia. Available online: https://encyclopedia.pub/entry/33374 (accessed on 09 July 2025).
Mencía S,  Alonso C,  Pallás-Alonso C,  López-Herce J. Pain in Fetuses, Neonates and Children. Encyclopedia. Available at: https://encyclopedia.pub/entry/33374. Accessed July 09, 2025.
Mencía, Santiago, Clara Alonso, Carmen Pallás-Alonso, Jesús López-Herce. "Pain in Fetuses, Neonates and Children" Encyclopedia, https://encyclopedia.pub/entry/33374 (accessed July 09, 2025).
Mencía, S.,  Alonso, C.,  Pallás-Alonso, C., & López-Herce, J. (2022, November 07). Pain in Fetuses, Neonates and Children. In Encyclopedia. https://encyclopedia.pub/entry/33374
Mencía, Santiago, et al. "Pain in Fetuses, Neonates and Children." Encyclopedia. Web. 07 November, 2022.
Pain in Fetuses, Neonates and Children
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This entry is adapted from the peer-reviewed paper 10.3390/children9111688

Pain can be defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. Pain consists of two features: nociception and emotional reaction.

analgesia pain children analgesics behavioral pain assessment

1. Introduction

Pain can be defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” [1]. Pain consists of two features: nociception and emotional reaction.
Perception of pain is individual and differs between children and adults. The sensation of pain is not only influenced by neurophysiological mechanisms but also by both psychological aspects and the environment [2]. These aspects affect and modulate the nociceptive sensation so that the same pathological situation may cause very different painful perceptions depending on the individual. In general, children pay maximum attention to pain, which could lead increased anxiety and fear of the painful sensation, magnifying the sensory experience [3][4].
Therefore, different pain management strategies are required in children than in adults, highlighting the importance of prior preparation and non-pharmacological interventions before performing any painful procedure in a child [5][6] (Table 1).
Table 1. Pain differences according to age.
Neonates and Infants Children Adults
Development of pain sensitivity Yes, undefined Yes, defined Yes, defined
Location of pain No No;
Yes in older children		 Yes
Verbal expression Cry Verbal;
Could be non-specific		 Verbal and specific
Pain response Important and generalized
(tachycardia, tachypnea, hypertension–hypotension, severe stress and agitation)		 Important in toddlers;Moderate in older children Mild
Difference between anxiety and pain No Only older children Yes
Clinical evaluation Physiological scales Physiological and verbal scales, non-numerical Numerical scales
Analgesic drugs Very few studies;
Empirical off-label treatment for most drugs;
Undefined doses		 Few studies;
Empirical off-label treatment for most drugs		 Many studies;
Well-defined doses
Side effects of analgesic drugs Severe systemic side effects (bradycardia, hypotension and respiratory arrest)
Psychomotor development effect?		 Moderate systemic side effects
Psychomotor development effect?		 Mild systemic side effects

2. Fetal Pain

2.1. Fetal Pain

Pain is a conscious and subjective experience and not just a response to noxious stimuli. For human beings to be able to experience pain, a series of physiologically mature neurological structures is needed. On the other hand, for the experience of pain to occur, other cognitive processes related to the state of consciousness and memory must be developed, which, in turn, allow an event to be discriminated as painful [7][8][9][10][11].
The development of neural pathways involved in pain pathophysiology begins early in fetal life, around the seventh week of gestation, followed by the development of the thalamus and neural connections in the cerebral cortex [7][8][9]. Therefore, some researchers suggest that fetal pain does not occur before 24 weeks of gestation because the structures of the central nervous system (CNS) required for pain perception. such as the cortex, spinal cord and thalamus are not fully developed [10]. However, other researchers argue that pain perception can occur, mediated by developmental structures, such as the subplate, between 12 and 20 weeks of gestation [11][12][13][14]. Additionally, behavioral changes associated with pain, such as simple motor responses, including crying and facial expressions, are described in fetuses and very premature neonates [15][16].

2.2. Fetal Pain Evaluation

Several physiological reactions in fetuses, such as crying, avoidance or changes in the levels of stress hormones, can be interpreted as signals of pain.
Magnetic resonance imaging (MRI) and fetal magnetoencephalographic imaging showed evoked responses to vibroacoustic and visual stimuli in the third trimester [17][18][19].
Ultrasound investigation has enabled the acquisition of behavioral characteristics in fetuses, such as crying [20][21], as well as fetal facial expressions of acute pain in surgery [22], as well as fetal movement in response to contact with an amniocentesis needle [23].
Fetuses exposed to a prolonged painful invasive procedures have increased concentrations of cortisol and beta endorphins in plasma [24][25].

2.3. Treatment of Fetal Pain in Fetal Surgery

Treatment of fetal pain is especially significant in fetal surgery. There are three main administration routes of fetal anesthesia and analgesia: uteroplacental transfer; intravenous, usually by the umbilical line; or intramuscularly [26]. Volatile anesthetics and opioids limit the fetal stress response, although they can produce cardiovascular fetal depression, although likely without side effects for short procedures [27].
Most researchers use deep general maternal anesthesia in ex-utero intrapartum therapy surgery to anesthetic the mother and the fetus and in fetoscopies the preferences are administrate the anesthesia and analgesia directly to the fetus, usually applying an intramuscular route or umbilical line [28][29][30][31][32][33][34][35][36].

3. Neonatal Pain

After painful stimulus, newborns have demonstrated in MRI scans that brain regions encoding sensory and affective components of pain responses are similar to those in adults [37].
Excessive or maintained pain exposure can be detrimental, causing adverse physiological effects and even long-term consequences [38][39][40]. Preterm infants, after experiencing pain, were reported to suffer hyperalgesia and allodynia, producing prolonged stress [41].
Infants born very preterm (<32 weeks), have received many pain-related insults in a vulnerable cerebral period, require special attention [38]. Repeated pain-related stress in very premature newborns is associated with alteration of brain development during the neonatal period, [42] as well as later functional cortical activity impairment with thinning of the brain cortex, white matter microstructure alterations and cognitive outcome at school age [43][44].

4. Pain in Children

Children usually feel pain differently than adults. The American Academy of Pediatrics (AAP) and the American Pain Society provided a general definition of pediatric pain: “the concept of pain and suffering goes far beyond a simple sensory experience. There are emotional, cognitive and behavioral components, along with developmental, environmental and sociocultural aspects” [45]. This definition underlines the importance of the subjectivity of pain [46]. Fear and anxiety produce suffering and increase the perception of pain in children, especially the fear of separation from their parents. An important goal of pain management is to eliminate the suffering associated with pain.

5. Pain Assessment

5.1. Concepts

The first step in the treatment of pain is its detection; several circumstances must first be taken into account:
-
The characteristics of the child: age, sex, sociocultural level and mood.
-
The characteristics of the pain: form of onset, intensity, evolution, duration, etiology and consequences that may be triggered [47].
The assessment of pain in children is complex, specifically in neonates, infants and preschool-aged children, because the expression of pain is undifferentiated, so it is often not possible to distinguish between pain, irritability and anxiety. Because they are not verbal, pain assessment tools rely on surrogated measures of physiologic, behavioral and biobehavioral responses to pain.
The most frequent physiologic indicators of pain are changes in heart and respiratory rate, blood pressure and oxygen saturation. The use of vital signs alone is not adequate because neonates and infants cannot maintain an autonomic response to pain and other factors, such a mechanical ventilation and drugs [48]. These indicators are also affected by other physiological stimuli, such a hypovolemia or fever.
The most used indicators are crying, facial activity, body movements, resting positions, agitation, consolability and sleeplessness. The assessment of these behavioral indicators depends on gestational age, mechanical ventilation and pharmacological treatment, and neurologic impairment and neuromuscular blockade may also decrease or alter responses to pain in critically ill children.

5.2. Neonatal Pain Assessment Tools

Several neonatal pain assessment tools are available [49][50][51]. Only three pain scales, PIPP-R, N-PASS and BPSN, are adapted to premature infants. The most commonly used pain scales are summarized in Table 2 [48][52]. Pain assessment tools should be selected with consideration of the population (full-term vs. preterm), context and type of pain (procedural vs. postoperative) [51][52].
Table 2. Neonatal pain scales.
Pain Scale Gestational Age Parameters Type of Pain Scale
Metric
PIPP-R (premature infant pain profile-revised) 26 weeks to term Heart rate and oxygen saturation.
Alertness, brow bulge, eye squeeze and nasolabial furrow		 Procedural and postoperative 0–21
CRIES (cries, requires oxygen, increased vital signs, expression, sleeplessness) 32–56 weeks Blood pressure, heart rate, oxygen saturation.
Cry, expression and sleeplessness		 Postoperative 0–10
NIPS (neonatal infant pain scale) 28–38 weeks Breathing pattern.
Facial expression, cry, arms, legs and alertness		 Procedural 0–7
COMFORT neo 24–42 weeks Respiratory response, blood pressure and heart rate.
Alertness, agitation, physical movements, muscle tone and facial tension		 Prolonged 8–40
NFCS (neonatal facial coding system) 25 weeks to term Brow bulge, eye squeeze, nasolabial furrow, open lips, stretched mouth, lip purse, taut tongue and chin quiver Procedural 0–10
N-PASS (neonatal pain, agitation and sedation scale) 0–100 days Heart rate, respiratory rate, blood pressure and oxygen saturation.
Crying or irritability, behavior state, facial expression, extremities or tone		 Acute and prolonged pain.
Also assesses sedation		 Pain 0–10
Sedation
−10–0
EDIN (échelle de la douleur inconfort noveau-né) 25–36 weeks Facial activity, body movements, quality of sleep, quality of contact with nurses and consolability Prolonged 0–15
BPSN (Bernese pain scale for neonates) 27–41 weeks Respiratory pattern, heart rate and oxygen saturation. Alertness, duration of cry, time to calm, skin color, brow bulge with eye squeeze and posture Procedural 0–27
Most tools adequately assess acute pain but not persistent or prolonged pain. Only two scales are adequate for prolonged pain (N-PASS and EDIN) [53]. The COMFORTneo scale was reported to be useful for evaluation of prolonged pain in [48].
Most parameters evaluated by these tools are subjective and require observation and recording in real time.
Other tools, such as neuroimaging (functional magnetic resonance imaging and near-infrared spectroscopy) and neurophysiologic techniques (amplitude-integrated electroencephalography, changes in skin conductance and heart rate variability) during acute or prolonged pain, were studied in [44][51]. Hormonal markers of stress, such as cortisol and parameters of oxidative stress, increase with pain stimuli, but they are not used in clinical settings at this time.

5.3. Pain Assessment Tools for Children

5.3.1. Clinical Scales

Clinical scales are the most commonly used instruments for pain assessment and monitoring [54]. The most frequently used are numerical, visual analogue or graphic scales adapted to the patient’s age. Through these scales, the patient can indicate the intensity of pain or the observer estimates the pain intensity based on the child’s behavior.
In the preverbal stage (1 month to 3 years), the scales mainly use facial expression and motor and physiological responses, such as crying. In the verbal stage (3 to 8 years) self-report can be tested using photographs and drawings of faces. From the age of 8 years onwards, verbal scale, numerical scale and graphic scales, as well as the visual analogue scale, can be used [55][56][57].
The most commonly used scales for the assessment of pain in child who are able to communicate are:
  • The visual analogue scale (VAS), which is represented on a 10 cm line between 0 (no pain) and 10 (worst pain imaginable). VAS < 4 indicates mild or mild–moderate pain, 4–6 indicates moderate–severe pain and >6 indicates severe pain.
  • The verbal numeric scale (VNS): the child expresses their perception of pain from 0 (no pain) to 10 (worst pain imaginable).
  • Graphic scales, which may consist of drawings of happy faces that change to sad according to the degree of pain, columns or thermometers that are more or less filled in, color ranges, etc.
In most children admitted to pediatric intensive care units (PICUs), it is not possible to use such scales, as many of the patients are sedated and unable to communicate. The same applies to children under 3 years of age in the preverbal stage. In such cases, the identification of pain requires tools based on changes in physiological parameters, facial expression or motor response to estimate the degree of pain [54][58].
Two scales have been validated for use in critically ill children:
  • The FLACC scale (face, leg, activity, cry, consolability) (Table 3), which considers facial expression, leg attitude, spontaneous activity, the presence and characteristics of crying and the ability to comfort or consolability, with scores ranging between 0 and 2 points for each item. A value of 0 indicates no pain, and scores of 9–10 indicate unbearable pain.
Table 3. FLACC scale (face, leg, activity, cry, consolability).
0 1 2
Face No particular expression or smile Occasional grimace or frown, withdrawn, disinterested. Frequent to constant quivering chin, clenched jaw
Legs Normal position or relaxed Uneasy, restless, tense Kicking or legs drawn up
Activity Crying quietly, normal position, moves easily. Squirming, shifting back and forth, tense. Arched, rigid or jerking.
Cry No cry (awake or asleep) Moans or whimpers; occasional complaint. Crying steadily, screams or sobs, frequent complaints.
Consolability Content, relaxed. Reassured by occasional touching, hugging or being talk to; distractible. Difficult to console or comfort.
No pain, 0; mild pain, 1–2; moderate pain, 3–5; severe pain, 6–8; extreme–maximum pain, 9–10.
2.
MAPS scale (multidimensional assessment pain scale) (Table 4). This scale is based on the observation of body movements and facial expression. It is a multidimensional scale that also includes physiological parameters, such as breathing, changes in blood pressure (BP) and heart rate (HR). Similar to the FLACC scale, it classifies pain on a scale from 0 (no pain) to 9–10 (unbearable pain) [59].
Table 4. MAPS scale (multidimensional assessment pain scale).
0 1 2
Vital signs: HR and/or BP Within baseline More than 10 bpm increase and/or more than 10 mmHg increase More than 10 bpm decrease and/or more than 10 mmHg decrease
Breathing pattern No change Development or increase in respiratory distress Severe respiratory distress
Facial expression Relaxed Grimace Grimace associated with silent or weak cry
Body movements No movements or purposeful movements Restless Rigid and/or limited body movements
State of arousal Calm or asleep Hyperreactive Shut down
No pain, 0; mild pain, 1–2; moderate pain, 3–5; severe pain, 6–8; extreme–maximum pain, 9–10.

5.3.2. Objective Pain Monitoring

Some monitors detect physiological changes that occur in association with painful stimuli and stress based on electromyograms, plethysmography, electrocardiograms, skin conductance or measurement of the diameter of the pupil. Such monitors can quantify the intensity of pain and the response to treatment. These parameters are objective, non-invasive, relatively easy to use and can be used at the patient’s bedside. However, they are unspecific (other non-pain stimulus, such as agitation, fear and stress, produce the same response) and are expensive. Therefore, they have not yet been applied in clinical settings [60][61]. Such monitors include:
Conductance skin impedance monitor (Medstorm Innovations, Oslo, Norway), which assesses the stress response through changes in skin conductance produced by sympathetic stimulation. It is non-invasive with rapid response but does not differentiate between agitation and pain and it is not able to measure baseline stress [62].
The analgesia nociception index (ANI), which is based on the RR variability of ECG intervals. This is a continuous line measurement of parasympathetic tone, which is part of the autonomic nervous system that assesses nociception [63][64].
The pain pupillary index (PPI) measurement, which provides real-time information from a video camera and infrared pupillary diameter [65].

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Subjects: Pediatrics
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Santiago Mencía
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Clara Alonso
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Carmen Pallás-Alonso
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Jesús López-Herce
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Revisions: 2 times (View History)
Update Date: 08 Nov 2022
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