Pain in children has been historically undertreated. This was
in part the result of misguided assumptions, such as children’s
inability to experience pain because of an immature nervous system
and the innocuous effects of untreated pain in children. In addition,
limited knowledge of pediatric drug metabolism prevented a clear
understanding of how to dose analgesics in children. Over the past
two decades, there has been significant progress in the understanding
of neuroanatomy, physiology, and pharmacology of analgesics in children,
which has led to considerable advancements in pain management. This
chapter discusses developmental anatomy and neurochemistry, pain
assessment, pharmacologic treatment of pain, and regional techniques
in pediatric patients.
The late fetus and infant are neurologically sophisticated in
their ability to transmit pain signals and respond to stress.1 Cutaneous
sensory nerve terminals are present in the perioral region at 7 weeks’ gestation
and spread to all body areas by 20 weeks’ gestation. Nerve
growth factors regulate the extension of peripheral nociceptive
fibers into the dorsal spinal cord, with the larger A fibers entering
prior to the C fibers at 8 to 12 weeks. At birth, A and C fiber
territories overlap in the developing substantia gelatinosa.2 Therefore,
the neonatal response to a nonspecific sensory stimulus is low threshold,
nonspecific, and poorly organized. Noxious and non-noxious stimuli
produce similar physiologic and behavioral infant responses, complicating
an accurate assessment of pain.
In the central nervous system (CNS), the full complement of cortical
neurons, approximately 1000 million, are present at 20 weeks’ gestation.
Pain transmission pathways complete myelination in the spine and
brain stem between 22 and 30 weeks’ gestation. Myelination
extends up to the thalamus by 30 weeks, and to the cortex by 37
weeks or term. Cortical descending inhibition develops post-term.
Excitatory and inhibitory neurotransmitters and neuromodulators
are present in the fetus, with the balance favoring excitation.
Calcitonin gene-related peptide (CGRP), substance P, and the glutamate-NMDA
systems are present at 8 to 10 weeks’ gestation. Enkephalin
and vasoactive intestinal peptide (VIP) appear at 10 to 14 weeks.
Catecholamines are present in late gestation, and serotonin at 6
weeks’ postnatal. Of note, the receptors for excitatory
neurotransmitters are numerous and widely distributed in the neonate,
regressing toward an adult system in the postnatal months. As well,
in the developing nervous system, inhibitory chemicals, such as
gamma-amino butyric acid (GABA) and glycine, may act as excitatory
transmitters. In an experimental murine model, the spinal cord concentration
of NMDA receptors, and their ligand-affinity, is greater in neonates
than in older animals. NK-1 receptor density is also maximal in
late fetal and early postnatal life; however, substance P levels
are lower than adult levels at birth.3
Regarding stress responses, the functional neuroendocrine pathways
between hypothalamus and pituitary are present at 21 weeks’ gestation.
Corticotrophin-releasing factor (CRF) may stimulate fetal ACTH and β-endorphin
from that time, and cortisol and β-endorphin increases
have been assayed following intrauterine sampling for exchange ...